The selective PPAR-α agonist, pemafibrate, is more effective at lowering serum triglyceride than the non-selective PPAR-α agonist, bezafibrate, according to results of a randomised crossover study in 60 patients with hypertriglyceridaemia (fasting triglyceride [TG] ≥150 mg/dL) treated by cardiologists in Japan.1,2
After 24 weeks of treatment, serum TG was reduced by -46.1% from baseline with pemafibrate 0.2mg/day compared to -34.7% with bezafibrate 400mg/day (p<0.001). There was also a significantly greater reduction in apoB with pemafibrate (-8.0% vs -3.1%, p=0.018), and a significantly greater increase in apoA-1 with pemafibrate (9.2% vs 5.7%, p=0.018, respectively).
Changes in LDL-C, HDL-C, apoB48 and Lp(a) were not significantly different between the two treatment groups. However, there was a significantly greater reduction in remnant-like particle cholesterol (RemL-C) with pemafibrate than with bezafibrate (-48.9% vs -36.8%, p<0.001). Liver enzyme levels (ALT and γ-GT) decreased with both drugs but the change was significantly greater with pemafibrate than with bezafibrate (p=0.048 and p=0.025 for ALT and γ-GT respectively). Serum creatinine levels increased with both treatments but the change was significantly greater with bezafibrate (5.72% vs 15.5%, p<0.001).
The incidence of adverse events (AEs) or serious AEs did not differ between the two treatments, though the number of patients with elevated creatinine levels (≥0.5 mg/dL and/or 25% from baseline) was significantly higher in the bezafibrate than the pemafibrate group (14/60 vs 3/60, p=0.004).
The results contribute further to discussions about the role of fibrates in atherosclerotic cardiovascular disease following the disappointing effects of pemafibrate on cardiovascular risk in the PROMINENT trial.3
- Nakamura A, Kagaya Y, Saito H, Kanazawa M, Sato K, Miura M, Kondo M, Endo H. Efficacy and Safety of Pemafibrate Versus Bezafibrate to Treat Patients with Hypertriglyceridemia: A Randomized Crossover Study. J Atheroscler Thromb. 2023 May 1;30(5):443-454.
- Nakamura A, Kagaya Y, Saito H, Kanazawa M, Sato K, Miura M, Kondo M, Endo H. Efficacy and Safety of Pemafibrate Versus Bezafibrate to Treat Patients with Hypertriglyceridemia: A Randomized Crossover Study. J Atheroscler Thromb. 2023 Jun 1;30(6):698-699. Erratum for: J Atheroscler Thromb. 2023 May 1;30(5):443-454.
- Das Pradhan A, Glynn RJ, Fruchart JC et al; PROMINENT Investigators. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med. 2022 Nov 24;387(21):1923-1934.