Background Peroxisome proliferator-activated receptor (PPAR) agonists are promising therapeutic agents for metabolic dysfunction-associated steatotic liver disease (MASLD), which increases cardiovascular risk. Methods We compared the efficacy of pemafibrate, a highly selective PPAR-α agonist, and bezafibrate, a non-selective PPAR-α agonist, in patients with coronary artery disease (CAD) and MASLD. This was a post-hoc analysis of a randomized, crossover study that treated hypertriglyceridemia with pemafibrate or bezafibrate for 24 weeks, followed by a crossover for another 24 weeks. Of the 60 enrolled patients, 21 were identified as having MASLD (fatty liver index FLI ≥ 60 and hepatic steatosis index HSI ≥ 36 as indicators). The primary outcomes were changes in serum alanine aminotransferase (ALT) levels and flow-mediated dilation (FMD). Secondary outcomes were changes in the FLI and HSI. Homeostasis model assessment of insulin resistance (HOMA-IR) was assessed as an exploratory outcome. Results The percentage reduction in ALT levels was significantly greater with pemafibrate treatment than with bezafibrate treatment (−23.1% vs. −9.2%, P = 0.035). FMD significantly increased in both groups, with no difference in the magnitude of the percentage change (P = 0.267). FLI significantly decreased in both groups with no difference in the magnitude of change (P = 0.983), while HSI was not significantly different before and after treatment in either group. Both treatments significantly lowered HOMA-IR; however, the decrease was similar between the groups (P = 0.724). Conclusions Pemafibrate is more effective than bezafibrate at reducing ALT levels while offering similar beneficial effects on insulin resistance and endothelial function in CAD patients with MASLD.
Nakamura et al. (Wed,) studied this question.
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