PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection

Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objecti...
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Autor*in:	Navarese, Eliano P. [verfasserIn] Podhajski, Przemysław [verfasserIn] Gurbel, Paul A. [verfasserIn] Grzelakowska, Klaudyna [verfasserIn] Ruscio, Eleonora [verfasserIn] Tantry, Udaya [verfasserIn] Magielski, Przemysław [verfasserIn] Kubica, Aldona [verfasserIn] Niezgoda, Piotr [verfasserIn] Adamski, Piotr [verfasserIn] Junik, Roman [verfasserIn] Przybylski, Grzegorz [verfasserIn] Pilaczyńska-Cemel, Marta [verfasserIn] Rupji, Manali [verfasserIn] Specchia, Giuseppe [verfasserIn] Pinkas, Jarosław [verfasserIn] Gajda, Robert [verfasserIn] Gorog, Diana A. [verfasserIn] Andreotti, Felicita [verfasserIn] Kubica, Jacek [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial

Übergeordnetes Werk:	Enthalten in: Journal of the American College of Cardiology - American College of Cardiology ; ID: gnd/1017722-X, New York, NY : Elsevier, 1983, 81, Seite 224-234
Übergeordnetes Werk:	volume:81 ; pages:224-234

DOI / URN:	10.1016/j.jacc.2022.10.030

Katalog-ID:	ELV009102272

Internformat


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024	7		\|a 10.1016/j.jacc.2022.10.030 \|2 doi
035			\|a (DE-627)ELV009102272
035			\|a (ELSEVIER)S0735-1097(22)07408-3
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100	1		\|a Navarese, Eliano P. \|e verfasserin \|0 (orcid)0000-0002-2355-4589 \|4 aut
245	1	0	\|a PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection
264		1	\|c 2023
336			\|a nicht spezifiziert \|b zzz \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)
650		4	\|a COVID-19
650		4	\|a death
650		4	\|a interleukin-6
650		4	\|a intubation
650		4	\|a PCSK9 inhibition
650		4	\|a randomized controlled trial
700	1		\|a Podhajski, Przemysław \|e verfasserin \|4 aut
700	1		\|a Gurbel, Paul A. \|e verfasserin \|4 aut
700	1		\|a Grzelakowska, Klaudyna \|e verfasserin \|4 aut
700	1		\|a Ruscio, Eleonora \|e verfasserin \|4 aut
700	1		\|a Tantry, Udaya \|e verfasserin \|4 aut
700	1		\|a Magielski, Przemysław \|e verfasserin \|4 aut
700	1		\|a Kubica, Aldona \|e verfasserin \|4 aut
700	1		\|a Niezgoda, Piotr \|e verfasserin \|4 aut
700	1		\|a Adamski, Piotr \|e verfasserin \|4 aut
700	1		\|a Junik, Roman \|e verfasserin \|4 aut
700	1		\|a Przybylski, Grzegorz \|e verfasserin \|4 aut
700	1		\|a Pilaczyńska-Cemel, Marta \|e verfasserin \|4 aut
700	1		\|a Rupji, Manali \|e verfasserin \|4 aut
700	1		\|a Specchia, Giuseppe \|e verfasserin \|4 aut
700	1		\|a Pinkas, Jarosław \|e verfasserin \|4 aut
700	1		\|a Gajda, Robert \|e verfasserin \|4 aut
700	1		\|a Gorog, Diana A. \|e verfasserin \|4 aut
700	1		\|a Andreotti, Felicita \|e verfasserin \|4 aut
700	1		\|a Kubica, Jacek \|e verfasserin \|4 aut
773	0	8	\|i Enthalten in \|a American College of Cardiology ; ID: gnd/1017722-X \|t Journal of the American College of Cardiology \|d New York, NY : Elsevier, 1983 \|g 81, Seite 224-234 \|h Online-Ressource \|w (DE-627)266884717 \|w (DE-600)1468327-1 \|w (DE-576)099603837 \|x 1558-3597 \|7 nnns
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912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_39
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912			\|a GBV_ILN_65
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912			\|a GBV_ILN_285
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912			\|a GBV_ILN_2004
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912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
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912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
936	b	k	\|a 44.85 \|j Kardiologie \|j Angiologie
951			\|a AR
952			\|d 81 \|h 224-234

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publishDate	2023
allfields	10.1016/j.jacc.2022.10.030 doi (DE-627)ELV009102272 (ELSEVIER)S0735-1097(22)07408-3 DE-627 ger DE-627 rda eng 610 DE-600 44.85 bkl Navarese, Eliano P. verfasserin (orcid)0000-0002-2355-4589 aut PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105) COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial Podhajski, Przemysław verfasserin aut Gurbel, Paul A. verfasserin aut Grzelakowska, Klaudyna verfasserin aut Ruscio, Eleonora verfasserin aut Tantry, Udaya verfasserin aut Magielski, Przemysław verfasserin aut Kubica, Aldona verfasserin aut Niezgoda, Piotr verfasserin aut Adamski, Piotr verfasserin aut Junik, Roman verfasserin aut Przybylski, Grzegorz verfasserin aut Pilaczyńska-Cemel, Marta verfasserin aut Rupji, Manali verfasserin aut Specchia, Giuseppe verfasserin aut Pinkas, Jarosław verfasserin aut Gajda, Robert verfasserin aut Gorog, Diana A. verfasserin aut Andreotti, Felicita verfasserin aut Kubica, Jacek verfasserin aut Enthalten in American College of Cardiology ; ID: gnd/1017722-X Journal of the American College of Cardiology New York, NY : Elsevier, 1983 81, Seite 224-234 Online-Ressource (DE-627)266884717 (DE-600)1468327-1 (DE-576)099603837 1558-3597 nnns volume:81 pages:224-234 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.85 Kardiologie Angiologie AR 81 224-234
spelling	10.1016/j.jacc.2022.10.030 doi (DE-627)ELV009102272 (ELSEVIER)S0735-1097(22)07408-3 DE-627 ger DE-627 rda eng 610 DE-600 44.85 bkl Navarese, Eliano P. verfasserin (orcid)0000-0002-2355-4589 aut PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105) COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial Podhajski, Przemysław verfasserin aut Gurbel, Paul A. verfasserin aut Grzelakowska, Klaudyna verfasserin aut Ruscio, Eleonora verfasserin aut Tantry, Udaya verfasserin aut Magielski, Przemysław verfasserin aut Kubica, Aldona verfasserin aut Niezgoda, Piotr verfasserin aut Adamski, Piotr verfasserin aut Junik, Roman verfasserin aut Przybylski, Grzegorz verfasserin aut Pilaczyńska-Cemel, Marta verfasserin aut Rupji, Manali verfasserin aut Specchia, Giuseppe verfasserin aut Pinkas, Jarosław verfasserin aut Gajda, Robert verfasserin aut Gorog, Diana A. verfasserin aut Andreotti, Felicita verfasserin aut Kubica, Jacek verfasserin aut Enthalten in American College of Cardiology ; ID: gnd/1017722-X Journal of the American College of Cardiology New York, NY : Elsevier, 1983 81, Seite 224-234 Online-Ressource (DE-627)266884717 (DE-600)1468327-1 (DE-576)099603837 1558-3597 nnns volume:81 pages:224-234 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.85 Kardiologie Angiologie AR 81 224-234
allfields_unstemmed	10.1016/j.jacc.2022.10.030 doi (DE-627)ELV009102272 (ELSEVIER)S0735-1097(22)07408-3 DE-627 ger DE-627 rda eng 610 DE-600 44.85 bkl Navarese, Eliano P. verfasserin (orcid)0000-0002-2355-4589 aut PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105) COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial Podhajski, Przemysław verfasserin aut Gurbel, Paul A. verfasserin aut Grzelakowska, Klaudyna verfasserin aut Ruscio, Eleonora verfasserin aut Tantry, Udaya verfasserin aut Magielski, Przemysław verfasserin aut Kubica, Aldona verfasserin aut Niezgoda, Piotr verfasserin aut Adamski, Piotr verfasserin aut Junik, Roman verfasserin aut Przybylski, Grzegorz verfasserin aut Pilaczyńska-Cemel, Marta verfasserin aut Rupji, Manali verfasserin aut Specchia, Giuseppe verfasserin aut Pinkas, Jarosław verfasserin aut Gajda, Robert verfasserin aut Gorog, Diana A. verfasserin aut Andreotti, Felicita verfasserin aut Kubica, Jacek verfasserin aut Enthalten in American College of Cardiology ; ID: gnd/1017722-X Journal of the American College of Cardiology New York, NY : Elsevier, 1983 81, Seite 224-234 Online-Ressource (DE-627)266884717 (DE-600)1468327-1 (DE-576)099603837 1558-3597 nnns volume:81 pages:224-234 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.85 Kardiologie Angiologie AR 81 224-234
allfieldsGer	10.1016/j.jacc.2022.10.030 doi (DE-627)ELV009102272 (ELSEVIER)S0735-1097(22)07408-3 DE-627 ger DE-627 rda eng 610 DE-600 44.85 bkl Navarese, Eliano P. verfasserin (orcid)0000-0002-2355-4589 aut PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105) COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial Podhajski, Przemysław verfasserin aut Gurbel, Paul A. verfasserin aut Grzelakowska, Klaudyna verfasserin aut Ruscio, Eleonora verfasserin aut Tantry, Udaya verfasserin aut Magielski, Przemysław verfasserin aut Kubica, Aldona verfasserin aut Niezgoda, Piotr verfasserin aut Adamski, Piotr verfasserin aut Junik, Roman verfasserin aut Przybylski, Grzegorz verfasserin aut Pilaczyńska-Cemel, Marta verfasserin aut Rupji, Manali verfasserin aut Specchia, Giuseppe verfasserin aut Pinkas, Jarosław verfasserin aut Gajda, Robert verfasserin aut Gorog, Diana A. verfasserin aut Andreotti, Felicita verfasserin aut Kubica, Jacek verfasserin aut Enthalten in American College of Cardiology ; ID: gnd/1017722-X Journal of the American College of Cardiology New York, NY : Elsevier, 1983 81, Seite 224-234 Online-Ressource (DE-627)266884717 (DE-600)1468327-1 (DE-576)099603837 1558-3597 nnns volume:81 pages:224-234 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.85 Kardiologie Angiologie AR 81 224-234
allfieldsSound	10.1016/j.jacc.2022.10.030 doi (DE-627)ELV009102272 (ELSEVIER)S0735-1097(22)07408-3 DE-627 ger DE-627 rda eng 610 DE-600 44.85 bkl Navarese, Eliano P. verfasserin (orcid)0000-0002-2355-4589 aut PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105) COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial Podhajski, Przemysław verfasserin aut Gurbel, Paul A. verfasserin aut Grzelakowska, Klaudyna verfasserin aut Ruscio, Eleonora verfasserin aut Tantry, Udaya verfasserin aut Magielski, Przemysław verfasserin aut Kubica, Aldona verfasserin aut Niezgoda, Piotr verfasserin aut Adamski, Piotr verfasserin aut Junik, Roman verfasserin aut Przybylski, Grzegorz verfasserin aut Pilaczyńska-Cemel, Marta verfasserin aut Rupji, Manali verfasserin aut Specchia, Giuseppe verfasserin aut Pinkas, Jarosław verfasserin aut Gajda, Robert verfasserin aut Gorog, Diana A. verfasserin aut Andreotti, Felicita verfasserin aut Kubica, Jacek verfasserin aut Enthalten in American College of Cardiology ; ID: gnd/1017722-X Journal of the American College of Cardiology New York, NY : Elsevier, 1983 81, Seite 224-234 Online-Ressource (DE-627)266884717 (DE-600)1468327-1 (DE-576)099603837 1558-3597 nnns volume:81 pages:224-234 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.85 Kardiologie Angiologie AR 81 224-234
language	English
source	Enthalten in Journal of the American College of Cardiology 81, Seite 224-234 volume:81 pages:224-234
sourceStr	Enthalten in Journal of the American College of Cardiology 81, Seite 224-234 volume:81 pages:224-234
format_phy_str_mv	Article
bklname	Kardiologie Angiologie
institution	findex.gbv.de
topic_facet	COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial
dewey-raw	610
isfreeaccess_bool	false
container_title	Journal of the American College of Cardiology
authorswithroles_txt_mv	Navarese, Eliano P. @@aut@@ Podhajski, Przemysław @@aut@@ Gurbel, Paul A. @@aut@@ Grzelakowska, Klaudyna @@aut@@ Ruscio, Eleonora @@aut@@ Tantry, Udaya @@aut@@ Magielski, Przemysław @@aut@@ Kubica, Aldona @@aut@@ Niezgoda, Piotr @@aut@@ Adamski, Piotr @@aut@@ Junik, Roman @@aut@@ Przybylski, Grzegorz @@aut@@ Pilaczyńska-Cemel, Marta @@aut@@ Rupji, Manali @@aut@@ Specchia, Giuseppe @@aut@@ Pinkas, Jarosław @@aut@@ Gajda, Robert @@aut@@ Gorog, Diana A. @@aut@@ Andreotti, Felicita @@aut@@ Kubica, Jacek @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	266884717
dewey-sort	3610
id	ELV009102272
language_de	englisch
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. 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author	Navarese, Eliano P.
spellingShingle	Navarese, Eliano P. ddc 610 bkl 44.85 misc COVID-19 misc death misc interleukin-6 misc intubation misc PCSK9 inhibition misc randomized controlled trial PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection
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topic_title	610 DE-600 44.85 bkl PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection COVID-19 death interleukin-6 intubation PCSK9 inhibition randomized controlled trial
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title	PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection
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title_full	PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection
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author_browse	Navarese, Eliano P. Podhajski, Przemysław Gurbel, Paul A. Grzelakowska, Klaudyna Ruscio, Eleonora Tantry, Udaya Magielski, Przemysław Kubica, Aldona Niezgoda, Piotr Adamski, Piotr Junik, Roman Przybylski, Grzegorz Pilaczyńska-Cemel, Marta Rupji, Manali Specchia, Giuseppe Pinkas, Jarosław Gajda, Robert Gorog, Diana A. Andreotti, Felicita Kubica, Jacek
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author-letter	Navarese, Eliano P.
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title_sort	pcsk9 inhibition during the inflammatory stage of sars-cov-2 infection
title_auth	PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection
abstract	Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)
abstractGer	Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)
abstract_unstemmed	Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)
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title_short	PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection
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author2	Podhajski, Przemysław Gurbel, Paul A. Grzelakowska, Klaudyna Ruscio, Eleonora Tantry, Udaya Magielski, Przemysław Kubica, Aldona Niezgoda, Piotr Adamski, Piotr Junik, Roman Przybylski, Grzegorz Pilaczyńska-Cemel, Marta Rupji, Manali Specchia, Giuseppe Pinkas, Jarosław Gajda, Robert Gorog, Diana A. Andreotti, Felicita Kubica, Jacek
author2Str	Podhajski, Przemysław Gurbel, Paul A. Grzelakowska, Klaudyna Ruscio, Eleonora Tantry, Udaya Magielski, Przemysław Kubica, Aldona Niezgoda, Piotr Adamski, Piotr Junik, Roman Przybylski, Grzegorz Pilaczyńska-Cemel, Marta Rupji, Manali Specchia, Giuseppe Pinkas, Jarosław Gajda, Robert Gorog, Diana A. Andreotti, Felicita Kubica, Jacek
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up_date	2024-07-06T22:00:00.723Z
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