LDL-C level reduction <25 mg/dL with alirocumab not tied to MACE reduction: Circulation
USA: Acute coronary syndrome (ACS) patients treated with alirocumab who achieved LDL-C levels <25 mg/dL versus 25–50 mg/d did not show any additional reduction in MACE risk, finds a recent study in the journal Circulation.
Recent guidelines have reduced recommended target low-density lipoprotein-cholesterol (LDL-C) levels for patients at high risk for major adverse cardiovascular events (MACE). Still, there is uncertainty on whether achieving LDL-C levels below conventional targets yields any additional benefit results. There is a limited inferences from prior analyses because patients who achieve lower versus higher LDL-C on lipid-lowering therapy differ in other characteristics prognostic for MACE and because few achieved very low LDL-C levels.
To overcome the above mentioned limitations, Gregory G. Schwartz, University of Colorado School of Medicine, Aurora, CO, and colleagues performed an analysis of the ODYSSEY OUTCOMES trial which compared alirocumab with placebo in 18,924 recent ACS patients receiving intensive or maximum-tolerated statin treatment.
Patients treated with alirocumab were classified in prespecified strata of LDL-C achieved at 4 months of treatment: <25 (n=3357), 25-50 (n=3692) or >50 mg/dL (n=2197). For each stratum, the researchers compared MACE (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) after month 4 in patients receiving placebo with similar baseline characteristics and adherence, using 1:1 propensity score matching (PSM).
Key findings of the study include:
· Across achieved LDL-C strata of the alirocumab group patients differed by baseline LDL-C, lipoprotein(a), use of intensive statin therapy, study medication adherence, and other demographic, medical history, biometric, and laboratory criteria.
· After PSM, characteristics were similar in corresponding patients of the alirocumab and placebo groups.
· Treatment hazard ratio (HR), 95% confidence interval (CI), and absolute risk reduction (ARR, number per 100 patient-years) for MACE were similar in those with achieved LDL-C <25 mg/dL (HR, 0.74; ARR, 0.92) or 25-50 mg/dL (HR, 0.74; ARR, 1.05).
· Patients with achieved LDL-C >50 mg/dL had poorer adherence and derived less benefit (HR, 0.87; ARR, 0.62).
· No safety concerns were associated with a limited period of LDL-C levels <15 mg/dL.
"After accounting for differences in baseline characteristics and adherence, patients treated with alirocumab who achieved LDL-C levels <25 mg/dL did not appear to derive further reduction in the risk of MACE compared to those who achieved LDL-C levels of 25-50 mg/dL," concluded the authors.
"Clinical Efficacy and Safety of Alirocumab after Acute Coronary Syndrome According to Achieved Level of Low-Density Lipoprotein Cholesterol: A Propensity Score-Matched Analysis of the ODYSSEY OUTCOMES Trial," is published in the journal Circulation.
DOI: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.049447
