PROMINENT: A Randomized Trial of Pemafibrate for Triglyceride Reduction in the Prevention of Cardiovascular Disease

Presented at the AHA Scientific Sessions 2022 by: Aruna D. Pradhan, MD - Minneapolis, MN, USA

Introduction and methods

Elevated triglyceride (TG) levels are associated with CV risk. However, prior strategies to lower TG with fibrates or niacin showed no effect on CV risk reduction. Treatment with icosapent ethyl did result in reduced CV risk, but the observed risk reduction could not be attributed to TG lowering. Post-hoc analyses of fibrate trials suggested that TG lowering in patients with T2DM, mild-to-moderate hypertriglyceridemia and low HDL-c may be beneficial.

The PROMINENT trial investigated the effect of pemafibrate on CV outcomes in patients with T2DM, TG 200-499 mg/dL and HDL ≤ 40 mg/dL. A total of 10,497 patients were randomized to pemafibrate 0.2 mg twice daily or placebo. All patients were on background LDL-c lowering therapy. The primary endpoint was MI, ischemic stroke, coronary revascularization or CV death. Median follow-up was 3.4 years.

Main results

• At 4 months, the between group percentage change between pemafibrate and placebo was -26.2% for TG (95%CI -28.4 to -24.1), -25.8% for VLDL-c (-27.8 to -23.9), -25.6% for remnant cholesterol (-27.3 to -24.0), and -27.6% for ApoCIII (-29.1 to -26.1).
• There was no difference between groups for the primary endpoint of MI, ischemic stroke, coronary revascularization or CV death (HR 1.03, 95% CI 0.91-1.15, P=0.67). Total mortality was also similar in both groups (HR 1.04, 95% CI 0.91-1.20).
• Safety results showed an increased risk of venous thromboembolism (HR 2.05, 95% CI 1.35-3.17) and renal adverse events (HR 1.12, 95% CI 1.04-1.20) in the pemafibrate group.
• In an exploratory analysis, pemafibrate reduced the risk of any liver disease (HR 0.83, 95% CI 0.69-0.99) and non-alcoholic fatty liver disease (HR 0.78, 95% CI 0.63-0.96).

Conclusion

Pemafibrate reduced TG, VLDL-c, remnant cholesterol and ApoCIII by 20 to 30% in patients with T2DM, mild-to-moderate hypertriglyceridemia and low HDL-c . However, pemafibrate did not reduce CV outcomes, compared with placebo in this population.

-Our reporting is based on the information provided at the AHA Scientific Sessions-

The results of this study were simultaneously published in N Engl J Med.