Effect of Pemafibrate on Cerebrovascular Atherosclerosis in Patients with Stroke and Hypertriglyceridemia.

Abstract

Aims: The Pemafibrate for Prevention of Atherosclerotic Diseases in Stroke (PPAR Stroke) study aimed to assess the effects of pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, on the progression of cerebrovascular atherosclerosis in patients with stroke and hypertriglyceridemia.

Methods: Ninety-nine patients (mean age, 65.6 years; male, 74.7%) with hypertriglyceridemia and a history of stroke or transient ischemic attack of non-cardioembolic origin were included in this prospective single-arm study. Hypertriglyceridemia was defined as a fasting serum triglyceride (TG) level ≥ 150 mg/dL. All patients were treated with pemafibrate (0.2 mg or 0.1 mg/day) for 2 years. The primary outcome was change in carotid intima-media thickness (IMT) from baseline at 2 years, as assessed using carotid ultrasonography. The secondary outcomes were changes in blood biomarker levels and progression of intracranial artery stenosis on magnetic resonance angiography.

Results: The mean TG level significantly decreased from 269 mg/dL at baseline to 139 mg/dL at 2 years (P＜0.001) and high-density lipoprotein cholesterol level increased from 49 to 54 mg/dL (P＜0.001), whereas low-density lipoprotein cholesterol level remained unchanged. Significant reductions in high-sensitivity C-reactive protein and interleukin-6 levels were also observed (P=0.003 and P=0.002, respectively). With regard to mean IMT in the internal carotid arteries, the difference was significant for the left side (1.59 mm at baseline vs. 1.52 mm at 2 years; P=0.009) and borderline significant for the right side (1.32 mm at baseline vs. 1.28 mm at 2 years; P=0.053). Among the 48 stenotic lesions in the intracranial arteries, regression and progression was observed in 9 (18.8%) and 4 (8.3%) cases, respectively.

Conclusions: Pemafibrate was observed to have TG-lowering and anti-inflammatory effects and could attenuate atherosclerosis progression in the intra- and extracranial arteries of patients with stroke and hypertriglyceridemia.