Evolocumab treatment in addition to statin therapy was found to lower cardiovascular risk in patients with metabolic syndrome (MetS) and stable atherosclerotic cardiovascular (CV) disease, according to the results of a randomized clinical trial published in JAMA Cardiology.
Patients (n=27,342) with stable atherosclerotic CV disease and on a statin regimen from the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk trial (FOURIER; ClinicalTrials.gov Identifier: NCT01764633), which was conducted between 2013 and 2016, were stratified according to the National Cholesterol Education Program Adult Treatment Panel III MetS criteria. Patients were randomly assigned to receive the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab (subcutaneous injection of 140 mg every 2 weeks or 420 mg per month) or placebo. Patients were followed for a median of 2.2 years.
Of the 59.8% patients with MetS, 19.5% met all 5 Adult Treatment Panel III MetS criteria, 35.1% met 4 criteria, and 45.4% met 3 criteria. Patients with vs without MetS differed significantly at baseline for age, sex ratio, rates of diabetes, hypertension, and peripheral artery disease, body mass index, levels of high density lipoprotein-C (HDL-C), triglyceride levels, and estimated glomerular filtration rate.
At baseline, the median low-density lipoprotein-C (LDL-C) levels for patients with MetS was 91.5 mg/dL (interquartile range [IQR], 79-109 mg/dL) and 92 mg/dL (IQR, 81-108 mg/dL) for patients without MetS. Evolocumab treatment was associated with a reduction in LDL-C levels in patients with and without MetS (median from baseline to week 48: from 92 mg/dL; IQR, 79-109 mg/dL to 30 mg/dL; IQR, 19-48 mg/dL, and from 92 mg/dL; IQR, 81-108 mg/Dl to 29 mg/dL; IQR, 18-44 mg/dL, respectively). Evolocumab treatment lowered the levels of other atherogenic lipids at 48 weeks to a comparable degree in participants with or without MetS: non-HDL-C (50% vs 55%, respectively), apolipoprotein B (47% vs 51%, respectively), triglyceride (16% vs 16%, respectively), and lipoprotein A (27% vs 28%, respectively). These reductions observed after 48 weeks of treatment with evolocumab were significant when compared with the placebo group (P <.001 for all).
After adjusting for all cofactors, patients with MetS were at increased risk for CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization (the study’s primary outcome; adjusted hazard ratio [HR], 1.31; 95% CI, 1.18-1.46; P <.001). Evolocumab also reduced the rate of CV death, myocardial infarction, or stroke in patients with and without MetS, compared with placebo (HR, 0.76; 95% CI, 0.68-0.86 and HR, 0.86; 95%CI, 0.74-1.01, respectively).
The incidence of new-onset diabetes was higher among patients with vs without MetS (11.7% vs 4.6%, respectively; P <.001), but comparable in participants receiving evolocumab vs placebo. All other adverse events were similar between groups with the exception of injection site reaction, which was more frequent among patients who received evolocumab, regardless of MetS status.
A potential limitation of this study is the strict inclusion criteria, which may limit the generalizability of results.
“These data suggest that treatment with evolocumab in patients with ASCVD and diabetes or MetS is efficacious and safe,” noted the study authors.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Deedwania P, Murphy S A, Scheen A, et al. Efficacy and safety of PCSK9 inhibition with evolocumab in reducing cardiovascular events in patients with metabolic syndrome receiving statin therapy. Secondary analysis from the FOURIER randomized clinical trial. [published online August 12, 2020] JAMA Cardiol. doi:10.1001/jamacardio.2020.3151