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

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) <30mL/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 mUmin/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).