Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial. (21st August 2020)

• Record Type: Journal Article
• Authors: Tuñón, José; Steg, Philippe Gabriel; Bhatt, Deepak L; Bittner, Vera A; Díaz, Rafael; Goodman, Shaun G; Jukema, J Wouter; Kim, Yong-Un; Li, Qian H; Mueller, Christian; Parkhomenko, Alexander; Pordy, Robert; Sritara, Piyamitr; Szarek, Michael; White, Harvey D; Zeiher, Andreas M; Schwartz, Gregory G
• Is Part Of: European heart journal. Volume 41:Number 42(2020)
• Page Start: 4114
• Page End: 4123
• Publication Date: 2020-08-21
• Subjects: PCSK9 inhibition -- Acute coronary syndrome -- Low-density lipoprotein cholesterol -- Chronic kidney disease -- Glomerular filtration rate -- Major adverse cardiovascular events; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehaa498
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Aims: Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function. Methods and results: ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8 ± 17.6 mL/min/1.73 m 2, and low-density lipoprotein cholesterol (LDL-C) was 92 ± 31 mg/dL. At 36 months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR ( P = 0.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death ( P = 0.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR ≥90 mL/min/1.73 m 2 ( n = 7470; hazard ratio 0.784, 95% confidence interval 0.670–0.919; P = 0.003) and 60 to <90 ( n = 9326; 0.833, 0.731–0.949; P = 0.006), but not in those with eGFR < 60 ( n = 2122; 0.974, 0.805–1.178; P = 0.784). Adverse events other than local injection-site reactions were similar in both groups across all categories of eGFR. Conclusions: In patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR > 60 mL/min/1.73 m 2 . Graphical Abstract: