TY - JOUR
T1 - Efficacy and safety of alirocumab and evolocumab
T2 - a systematic review and meta-analysis of randomized controlled trials
AU - Guedeney, Paul
AU - Giustino, Gennaro
AU - Sorrentino, Sabato
AU - Claessen, Bimmer E.
AU - Camaj, Anton
AU - Kalkman, Deborah N.
AU - Vogel, Birgit
AU - Sartori, Samantha
AU - de Rosa, Salvatore
AU - Baber, Usman
AU - Indolfi, Ciro
AU - Montalescot, Gilles
AU - Dangas, George D.
AU - Rosenson, Robert S.
AU - Pocock, Stuart J.
AU - Mehran, Roxana
N1 - Funding Information: Idorsia, Lilly, Europa, Elsevier, Fédération Franc¸aise de Cardiologie, ICAN, Medtronic, Journal of the American College of Cardiology, Lead-Up, Menarini, MSD, Novo-Nordisk, Pfizer, Sanofi, Servier, The Mount Sinai School, TIMI Study Group, and WebMD. R.M. has received consulting fees from Abbott Laboratories; Abiomed (spouse); Boston Scientific; Bracco Group; Medscape/Web MD; Siemens Medical Solutions; The Medicines Company (spouse), PLx Opco, Inc,/dba PLx Pharma Inc. (scientific advisory board), Regeneron Pharmaceuticals Inc. (personal - no fee), Roivant Sciences, Inc.; Spectranetics/Phillips/Volcano Corporation (paid to the institution), Sanofi (consultant), janssen Pharmaceuticals, research funding to the institution from Astrazeneca; Bayer; Beth Israel Deaconess; BMS; CSL Behring; Eli Lilly/DSI; Medtronic; Novartis Pharmaceuticals; OrbusNeich; PLC/Renal Guard and Regeneron Pharmaceuticals, Inc.; Holds equity (<1%) in Claret Medical and Elixir Medical; is advisory/ speaker for Medteligence (Janssen), advisory board for Bristol-Meyers Squibb (funding to institution), Data safety and monitoring board membership (paid to the institution) for Watermark Research Partners. G.D. has received grants (to the institution) from The Medicines Company (modest level), has served on advisory board for Abbott Vascular, Boston Scientific and Philips, has been a consultant for biosensor, Abiomed and declares research grant to the institution from PLC (Renalguard) and Osprey Medical. U.B. has received speaker honoraria from Boston Scientific and AstraZeneca. S.J.P. has served on Steering Committees or Data Monitoring Committees for trials sponsored by Abbott Vascular, Amirin, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Edwards Lifesciences, Idorsia, Medtronic, Novartis, and Vifor. R.S.R. has received research grants from Akcea, Amgen, Astra Zeneca, Medicines Company, and Regeneron; has received consulting fees/honoraria from Akcea, Amgen, Kowa, and Pfizer; and has stock holdings in MediMergent, and royalties from UpToDate. All other authors have reported that they have no relationships relevant to the contents of this article to disclose. Publisher Copyright: © The Author(s) 2019. Published on behalf of the European Society of Cardiology. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Aims The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease. Methods We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocu- and results mab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin–kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74–0.86; I2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67–0.89; I2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78–0.89; I2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97). Conclusion Proprotein convertase subtilisin–kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.
AB - Aims The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease. Methods We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocu- and results mab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin–kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74–0.86; I2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67–0.89; I2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78–0.89; I2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97). Conclusion Proprotein convertase subtilisin–kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.
KW - Alirocumab
KW - Cholesterol-lowering therapies
KW - Evolocumab
KW - PCSK9
UR - http://www.scopus.com/inward/record.url?scp=85127578102&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/eurheartj/ehz430
DO - https://doi.org/10.1093/eurheartj/ehz430
M3 - Review article
C2 - 31270529
SN - 0195-668X
VL - 43
SP - E17-E25
JO - European Heart journal
JF - European Heart journal
IS - 7
ER -