Key result
Evacetrapib shows no benefit over placebo for major cardiovascular events in patients with diabetes.
Why the study?
HDL levels are inversely associated with cardiovascular risk and CETP inhibition with evacetrapib increases HDL and reduces LDL, motivating evaluation of its clinical impact in patients with diabetes mellitus.
Does evacetrapib reduce cardiovascular events in patients with diabetes mellitus at high risk for vascular outcomes?
RCT (n=8,236)
Does evacetrapib reduce cardiovascular events in patients with diabetes mellitus at high risk for vascular outcomes?
Hazard Ratio: 0.95 (95% CI 0.85–1.07)
Absolute Event Rate: 14.5% vs 16%
p-value: p=0.38
Despite improving HDL, LDL, and HbA1c levels, the CETP inhibitor evacetrapib did not reduce cardiovascular events in high-risk patients with diabetes.
Evacetrapib yields no CV benefit in high-risk diabetes despite lipid and HbA1c shifts; leaves open CETP inhibition effects in this population.
BACKGROUND: High-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition with evacetrapib results in a marked increase in HDL and reduction in low-density lipoprotein (LDL) levels. We evaluated the impact of treatment with evacetrapib versus placebo in the subset of 8236 patients with diabetes mellitus (DM) enrolled in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes trial. METHODS AND RESULTS: Time to first occurrence of any component of the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, revascularization, and hospitalization for unstable angina was compared among patients with DM randomized to treatment with evacetrapib (n=4127) or placebo (n=4109) over a median of 26 months of follow-up. The mean baseline LDL at initiation was 80 mg/dL with a mean baseline HDL of 44 mg/dL. In patients with DM, evacetrapib resulted in a 131% mean increase in HDL levels and a 32% mean decrease in LDL at 3 months that was sustained during the course of the trial. At 6 months, hemoglobin A1c (HbA1c) levels were lower with evacetrapib than placebo (7.08% vs 7.15%, p=0.023). Composite event rates were higher in patients with DM than without DM (Kaplan-Meier estimates: 15.2% vs 10.6%, HR 1.46, 95% CI 1.30 to 1.64, p<0.001). In the DM group, event rates for the composite endpoint (14.5% evacetrapib vs 16% placebo, HR 0.95, 95% CI 0.85 to 1.07, p=0.38) and individual components of the composite were similar for both evacetrapib and placebo groups. No significant treatment interaction between treatment assignment and diabetes status was noted. CONCLUSION: Despite a favorable increase in HDL, and decreases in LDL and HbA1c levels in patients with DM, we observed no benefits of treatment with evacetrapib on prespecified clinical outcomes in this high-risk population.
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Menon et al. (2020) conducted an RCT in Diabetes mellitus at high risk for vascular outcomes (n=8,236). Evacetrapib vs. Placebo was evaluated on Composite endpoint of cardiovascular death, myocardial infarction, stroke, revascularization, and hospitalization for unstable angina (HR 0.95, 95% CI 0.85 to 1.07, p=0.38). Evacetrapib did not significantly reduce the primary composite cardiovascular endpoint compared to placebo in patients with diabetes (14.5% vs 16.0%; HR 0.95; 95% CI 0.85-1.07; p=0.38).
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