Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk

The PROMINENT trial assessed whether pemafibrate, a selective PPARα modulator could reduce cardiovascular events in patients with type 2 diabetes, moderate hypertriglyceridemia (200–499 mg/dL), and low HDL cholesterol (≤40 mg/dL). Among 10,497 patients, pemafibrate significantly lowered triglycerides (–26.2%), VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III by ~25–28% compared to placebo over 4 months. However, cardiovascular event rates including myocardial infarction, stroke, coronary revascularization, and cardiovascular death were similar between groups (HR: 1.03; 95% CI: 0.91–1.15). No subgroup (e.g., primary vs. secondary prevention, statin intensity, baseline lipid profiles) showed differential benefit. Adverse renal events and venous thromboembolism occurred more often in the pemafibrate group, while hepatic events and nonalcoholic fatty liver disease were less frequent. The trial concluded that triglyceride lowering alone, even with favorable shifts in remnant particles, did not reduce cardiovascular risk in statin-treated patients—suggesting the need for therapies that enhance remnant clearance rather than conversion to LDL particles.

The PROMINENT trial assessed whether pemafibrate, a selective PPARα modulator could reduce cardiovascular events in patients with type 2 diabetes, moderate hypertriglyceridemia (200–499 mg/dL), and low HDL cholesterol (≤40 mg/dL). Among 10,497 patients, pemafibrate significantly lowered triglycerides (–26.2%), VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III by ~25–28% compared to placebo over 4 months. However, cardiovascular event rates including myocardial infarction, stroke, coronary revascularization, and cardiovascular death were similar between groups (HR: 1.03; 95% CI: 0.91–1.15). No subgroup (e.g., primary vs. secondary prevention, statin intensity, baseline lipid profiles) showed differential benefit. Adverse renal events and venous thromboembolism occurred more often in the pemafibrate group, while hepatic events and nonalcoholic fatty liver disease were less frequent. The trial concluded that triglyceride lowering alone, even with favorable shifts in remnant particles, did not reduce cardiovascular risk in statin-treated patients—suggesting the need for therapies that enhance remnant clearance rather than conversion to LDL particles.