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

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 m2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8 ± 17.6 mL/min/1.73 m2, 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 m2 (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 m2.

Long-Term Exposure to Ambient Fine Particulate Matter and Incidence of Major Cardiovascular Diseases: A Prospective Study of 0.5 Million Adults in China

“… 29 , 34 The endpoints of interest are defined as the first hospitalization event (during the follow-up period) from major CVD, including total CVD (ICD-10; I00–I99), ischemic heart disease (IHD; I20–I25), acute myocardial infarction (MI, I21), total stroke (I60–I61, I63–I64, and I69), hemorrhagic stroke (I61), and ischemic stroke (I63). We also derived composite endpoints of major adverse cardiovascular events (MACE; fatal IHD plus nonfatal MI, IS, or unstable angina; I21–I23, I60–I61, I63, and I64 when nonfatal; I00–I20, I24–I25, I27–I59, I62, I65–I88, and I95–I99 when fatal), 35 major vascular events (MVE, fatal CVD, I00–I99; nonfatal MI, I21–I23; nonfatal major stroke, I60, I61, I63, I64, I69.0, I69.1, I69.3, and I69.4), 36 and major coronary events (MCE; fatal IHD plus nonfatal MI; I21–I23; I20, I24, or I25 when fatal) commonly examined in previous cardiovascular epidemiological studies and clinical trials. 36 Participants without the endpoints of interest were censored upon death, loss to follow-up ( n = 5302), or 31 December 2017, whichever came sooner.…”

Prevalence and Prognostic Value of Heart Failure Stages: An Elderly Inpatient Based Cohort Study

“…The composite endpoint was 1-year major adverse cardiovascular events (MACE), defined as the classical compound endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death (17), and other cardiovascular events requiring hospitalization (unstable angina, severe arrhythmia, HF) (18). We confirmed the MACE occurrence through telephone interviews with the participant or caregiver 1 year after the date of signing informed consent, and through medical record review, if necessary.…”

Dyslipidemia in Chronic Kidney Disease: Contemporary Concepts and Future Therapeutic Perspectives

“…Involved in the degradation of the LDL receptor, PCSK9 inhibition has revolutionized the treatment of dyslipidemia. The randomized controlled trials provided robust evidence on their potency in reducing adverse cardiovascular events [82], being also efficacious in participants with mild-to-moderate renal dysfunction (Table 2) [64, 66]. Unfortunately, none of those trials enrolled patients with severe or dialysis-dependent CKD which creates inevitable gaps in evidence.…”