Captopril
Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (stru...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Plosker, Greg L. [verfasserIn] McTavish, Donna [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
1995 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Drugs & aging - Berlin [u.a.] : Springer, 1991, 7(1995), 3 vom: Sept., Seite 226-253 |
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| Übergeordnetes Werk: |
volume:7 ; year:1995 ; number:3 ; month:09 ; pages:226-253 |
| Links: |
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| DOI / URN: |
10.2165/00002512-199507030-00007 |
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| Katalog-ID: |
SPR033227985 |
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| 520 | |a Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... | ||
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10.2165/00002512-199507030-00007 doi (DE-627)SPR033227985 (SPR)00002512-199507030-00007-e DE-627 ger DE-627 rakwb eng 610 ASE Plosker, Greg L. verfasserin aut Captopril 1995 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... Adis International Limited (dpeaa)DE-He213 Acute Myocardial Infarction (dpeaa)DE-He213 Angiotensin Converting Enzyme (dpeaa)DE-He213 Captopril (dpeaa)DE-He213 Coronary Blood Flow (dpeaa)DE-He213 McTavish, Donna verfasserin aut Enthalten in Drugs & aging Berlin [u.a.] : Springer, 1991 7(1995), 3 vom: Sept., Seite 226-253 (DE-627)327644281 (DE-600)2043689-0 1179-1969 nnns volume:7 year:1995 number:3 month:09 pages:226-253 https://dx.doi.org/10.2165/00002512-199507030-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 AR 7 1995 3 09 226-253 |
| spelling |
10.2165/00002512-199507030-00007 doi (DE-627)SPR033227985 (SPR)00002512-199507030-00007-e DE-627 ger DE-627 rakwb eng 610 ASE Plosker, Greg L. verfasserin aut Captopril 1995 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... Adis International Limited (dpeaa)DE-He213 Acute Myocardial Infarction (dpeaa)DE-He213 Angiotensin Converting Enzyme (dpeaa)DE-He213 Captopril (dpeaa)DE-He213 Coronary Blood Flow (dpeaa)DE-He213 McTavish, Donna verfasserin aut Enthalten in Drugs & aging Berlin [u.a.] : Springer, 1991 7(1995), 3 vom: Sept., Seite 226-253 (DE-627)327644281 (DE-600)2043689-0 1179-1969 nnns volume:7 year:1995 number:3 month:09 pages:226-253 https://dx.doi.org/10.2165/00002512-199507030-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 AR 7 1995 3 09 226-253 |
| allfields_unstemmed |
10.2165/00002512-199507030-00007 doi (DE-627)SPR033227985 (SPR)00002512-199507030-00007-e DE-627 ger DE-627 rakwb eng 610 ASE Plosker, Greg L. verfasserin aut Captopril 1995 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... Adis International Limited (dpeaa)DE-He213 Acute Myocardial Infarction (dpeaa)DE-He213 Angiotensin Converting Enzyme (dpeaa)DE-He213 Captopril (dpeaa)DE-He213 Coronary Blood Flow (dpeaa)DE-He213 McTavish, Donna verfasserin aut Enthalten in Drugs & aging Berlin [u.a.] : Springer, 1991 7(1995), 3 vom: Sept., Seite 226-253 (DE-627)327644281 (DE-600)2043689-0 1179-1969 nnns volume:7 year:1995 number:3 month:09 pages:226-253 https://dx.doi.org/10.2165/00002512-199507030-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 AR 7 1995 3 09 226-253 |
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10.2165/00002512-199507030-00007 doi (DE-627)SPR033227985 (SPR)00002512-199507030-00007-e DE-627 ger DE-627 rakwb eng 610 ASE Plosker, Greg L. verfasserin aut Captopril 1995 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... Adis International Limited (dpeaa)DE-He213 Acute Myocardial Infarction (dpeaa)DE-He213 Angiotensin Converting Enzyme (dpeaa)DE-He213 Captopril (dpeaa)DE-He213 Coronary Blood Flow (dpeaa)DE-He213 McTavish, Donna verfasserin aut Enthalten in Drugs & aging Berlin [u.a.] : Springer, 1991 7(1995), 3 vom: Sept., Seite 226-253 (DE-627)327644281 (DE-600)2043689-0 1179-1969 nnns volume:7 year:1995 number:3 month:09 pages:226-253 https://dx.doi.org/10.2165/00002512-199507030-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 AR 7 1995 3 09 226-253 |
| allfieldsSound |
10.2165/00002512-199507030-00007 doi (DE-627)SPR033227985 (SPR)00002512-199507030-00007-e DE-627 ger DE-627 rakwb eng 610 ASE Plosker, Greg L. verfasserin aut Captopril 1995 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... Adis International Limited (dpeaa)DE-He213 Acute Myocardial Infarction (dpeaa)DE-He213 Angiotensin Converting Enzyme (dpeaa)DE-He213 Captopril (dpeaa)DE-He213 Coronary Blood Flow (dpeaa)DE-He213 McTavish, Donna verfasserin aut Enthalten in Drugs & aging Berlin [u.a.] : Springer, 1991 7(1995), 3 vom: Sept., Seite 226-253 (DE-627)327644281 (DE-600)2043689-0 1179-1969 nnns volume:7 year:1995 number:3 month:09 pages:226-253 https://dx.doi.org/10.2165/00002512-199507030-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 AR 7 1995 3 09 226-253 |
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Enthalten in Drugs & aging 7(1995), 3 vom: Sept., Seite 226-253 volume:7 year:1995 number:3 month:09 pages:226-253 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033227985</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519172917.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s1995 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00002512-199507030-00007</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033227985</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00002512-199507030-00007-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Plosker, Greg L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Captopril</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1995</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. 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Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... |
| abstractGer |
Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... |
| abstract_unstemmed |
Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. Subsequent analysis of data from the SAVE trial indicates that captopril effectively redu... |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033227985</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519172917.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s1995 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00002512-199507030-00007</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033227985</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00002512-199507030-00007-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Plosker, Greg L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Captopril</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1995</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58 000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients. In the US, captopril has been approved for use in patients with left ventricular dysfunction after myocardial infarction (the study population of the SAVE trial). Other patient groups also likely to benefit from captopril therapy after myocardial infarction are clinically stable patients with clinical signs of congestive heart failure and those with an anterior infarction or a previous infarction; however, it is noteworthy that captopril has demonstrated survival benefits in large studies of relatively unselected patient populations (i.e. including both high- and low-risk patients). Accordingly, captopril represents an important advance in the management of patients after acute myocardial infarction. Pharmacodynamic Properties Captopril attenuated ventricular remodelling (structural changes including infarct expansion and thinning resulting from stretching of the infarct zone and rearrangement of myocytes) after myocardial infarction in several animal studies and significantly improved survival in the rat model of myocardial infarction. These outcomes have subsequently been confirmed in human studies, and possibly result from a balanced reduction in preload and afterload with captopril, although other mechanisms may also be involved. Inhibition of angiotensin converting enzyme (ACE) by captopril reduces angiotensinII formation, and subsequent vasodilation may improve oxygen supply and demand, thus providing anti-ischaemic and cardioprotective effects. Captopril attenuated reductions in coronary blood flow both in conditions of ischaemia and normal oxygenation in animal models. Similar effects were noted in patients with coronary artery disease, probably as a result of ACE inhibition in coronary circulation and/or local tissue sites. Other mechanisms may also be involved in the potentially anti-ischaemic and cardioprotective effects of captopril, such as potentiation of bradykinin activity, enhanced prostaglandin synthesis and inhibition of catecholamine release, although studies evaluating these effects have produced equivocal or somewhat conflicting results. There is evidence that captopril is capable of scavenging oxygen free radicals, which are thought to be at least partially responsible for myocardial injury during ischaemia and reperfusion. The frequency of reperfusion arrhythmias was reduced by captopril in some animal studies of myocardial ischaemia/reperfusion. Baroreflex sensitivity, which is often depressed after myocardial infarction and appears to be an indicator of poor prognosis, was significantly increased in patients receiving captopril post-infarction. The concept that captopril may act as a sulfhydryl donor for vascular tissue, thereby potentiating the effects of nitrates and attenuating nitrate tolerance during more prolonged nitrate administration, is supported by data from in vitro and in vivo studies; however, data are preliminary and this issue remains controversial. Pharmacokinetic Properties The oral bioavailability of captopril in healthy fasting volunteers is approximately 60%, and coadministration of food or antacids reduces the bioavailability of captopril by 25 to 50%. Peak plasma captopril concentration (achieved ≈1 hour after administration) and area under the plasma concentration-time curve are linearly related to dose over a wide range of doses (10 to 150mg). Mean volume of distribution at steady-state is approximately 0.70 to 0.75 L/kg, and captopril is about 30% bound to plasma proteins. Approximately 50% of captopril reaching the systemic circulation is metabolised to disulphide compounds which, along with captopril, are primarily excreted by the kidneys. Mean elimination half-life of captopril is approximately 1.7 hours and increases linearly with increasing renal dysfunction. In general, pharmacokinetic values of captopril were similar in healthy elderly volunteers (aged 65 to 75 years) and in a younger historical control group (aged 18 to 35 years). Therapeutic Efficacy When added to standard therapy in patients after acute myocardial infarction, early initiation of captopril within 24 hours of signs and symptoms of myocardial infarction reduced 5-week mortality compared with placebo (7.19 vs 7.69%; p = 0.02) in the 4th International Study of Infarct Survival (ISIS-4). This study included more than 58 000 patients randomised according to a factorial design to receive: 1 month of treatment with oral captopril titrated to 50mg twice daily or placebo; oral controlled-release isosorbide mononitrate titrated to 60mg each morning or placebo; intravenous magnesium sulphate or no infusion (nonblind control). Neither oral nitrate nor intravenous magnesium therapy improved survival in this study. Approximately 5 lives were saved per 1000 patients treated with captopril for 1 month, and this survival benefit appeared to remain at 1 year after myocardial infarction. These data are supported by interim early mortality results of the Chinese Cardiac Study which also showed that approximately 5 lives were saved per 1000 patients treated with captopril for 1 month. Both ISIS-4 and the Chinese Cardiac Study included relatively unselected populations comprised of both high- and low-risk patients after acute myocardial infarction. In the Survival and Ventricular Enlargement (SAVE) trial, later initiation of captopril therapy (within 3 to 16 days of myocardial infarction) also reduced mortality in 2231 patients with left ventricular dysfunction (ejection fraction ≤40%), but without overt heart failure or symptoms of myocardial ischaemia, at the time of randomisation. In this group of high-risk patients, mortality from all causes was reduced by 19% (p = 0.019), from 275 deaths among 1116 placebo recipients (24.6%) to 228 deaths among 1115 captopril recipients (20.4%). In absolute terms, about 40 to 50 lives were saved per 1000 patients treated with captopril over this period. Captopril reduced the number of deaths resulting from cardiovascular events by 21% compared with placebo (p = 0.014), and significantly decreased the frequency of other cardiovascular events, such as development of congestive heart failure necessitating unblinded ACE inhibitor treatment or hospitalisation. 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