Draft
Background
High triglyceride levels are associated with increased cardiovascular risk, but it is uncertain whether lowering these levels will reduce the risk of cardiovascular events. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.
Methods
In a multicenter, double-blind, randomized, controlled trial, we randomized patients with type 2 diabetes, mild to moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels. 40 mg per deciliter or less to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or unable to receive statin therapy without side effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or less. The primary efficacy endpoint was a composite of nonfatal myocardial infarction, ischemic stroke, coronary artery disease, or death from cardiovascular causes.
Results
Among 10,497 patients (66.9% with prior cardiovascular disease), median baseline fasting triglyceride levels were 271 mg per deciliter, HDL cholesterol levels were 33 mg per deciliter, and LDL cholesterol levels were 78 mg per deciliter. The average follow-up was 3.4 years. Compared to placebo, the effect of pemafibrate on lipid levels in 4 months was -26.2% for triglycerides, -25.8% for very low-density lipoprotein (VLDL) cholesterol, -25.6% for residual cholesterol (cholesterol is transported in triglyceride-rich). Lipoproteins after lipolysis and lipoprotein modification), -27.6% for apolipoprotein C-III and 4.8% for apolipoprotein B. The primary end point event occurred in 572 patients in the pemafibrate group and in 560 in the placebo group (hazard ratio). , 1.03; 95% confidence interval, 0.91 to 1.15), with no clear improvement in outcome in any specific subgroup. The overall incidence of serious adverse events was not significantly different between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of non-alcoholic fatty liver disease.
Conclusions
In patients with type 2 diabetes, mild to moderate hypertriglyceridemia, low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower than in those receiving placebo, although pemafibrate lowered triglyceride, VLDL cholesterol. Residual cholesterol, and apolipoprotein C-III levels. (Sponsored by the Cowa Research Institute; PROMINENT ClinicalTrials.gov no. NCT03071692.)