When added to high-intensity statin therapy in patients with acute coronary syndrome (ACS), evolocumab quickly and significantly reduced low-density lipoprotein cholesterol (LDL-C) levels to recommended target levels, according to research published in the Journal of the American College of Cardiology.
The risk for recurrent ischemic events is particularly high for patients with ACS, and lowering LDL-C levels is critical for reducing cardiovascular morbidity and mortality in this population. In this study, the researchers assessed the safety, efficacy, and feasibility of evolocumab, an LDL-C-lowering drug with rapid onset of action, during the acute, in-hospital, high-intensity statin therapy stage.
The study (Evolocumab for Early Reduction of LDL-Cholesterol Levels in Patients With Acute Coronary Syndromes [EVOPACS], ClinicalTrials.gov Identifier: NCT03287609) was an investigator-initiated, double-blind, placebo-controlled trial with 308 patients. Inclusion criteria included diagnosis of ACS as defined by current guidelines and an LDL-C level higher than guideline recommendations (≥70 mg/dL for prior treatment with high-intensity statin, ≥90 mg/dL for prior treatment with low- or moderate-intensity statins, or ≥125 mg/dL with no prior statin treatment). Patients were randomly assigned to receive evolocumab 420 mg subcutaneously or placebo at baseline and again at 4 weeks. The primary end point was percentage change in calculated LDL-C from baseline to 8 weeks.
From baseline to week 8, a significant change in LDL-C of -77.1%±15.8% was demonstrated in the evolocumab group vs a change of -35.4%±26.6% in the placebo group. Furthermore, at the 8-week assessment, a reduction in LDL-C to the target level of <70 mg/dL was seen in 95.7% of patients receiving evolocumab, with some patients seeing results as early as 4 weeks after treatment initiation. No significant differences in adverse events were seen between the treatment and placebo groups.
Limitations of the study included oversight of prespecification of elevated triglyceride levels as an exclusionary criterion for the study, which slightly reduced the number of patients for whom planned outcome analyses could be reliably applied. The investigators also did not measure lipid levels before the planned 4-week assessment; therefore, they could not assess efficacy of evolocumab in the earlier stages of therapy.
The researchers concluded that “in patients presenting with ACS, evolocumab initiated in-hospital on top of high-intensity statin therapy was well tolerated and resulted in substantial reduction in LDL-C levels after 8 weeks” and “allowed rapid attainment of currently recommended target levels [of LDL-C].”
This study was supported by Amgen Inc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS) [published online August 31, 2019]. J Am Coll Cardiol. doi:10.1016/j.jacc.2019.08.010