Effects of Pemafibrate in Patients with Stroke and Hypertriglyceridemia: Baseline Cerebral Artery Diseases and 3-Month Laboratory Outcomes

J Atheroscler Thromb. 2022 Jul 1;29(7):1020-1030. doi: 10.5551/jat.63036. Epub 2021 Jul 9.

Abstract

Aims: The role of hypertriglyceridemia in stroke is poorly understood. The Pemafibrate for Prevention of Atherosclerotic Diseases in Stroke (PPAR Stroke) study was designed to assess the effects of a novel selective peroxisome proliferator-activated receptor alpha modulator, pemafibrate, on vascular outcomes in stroke patients with hypertriglyceridemia.

Methods: This was a prospective single-arm study including 74 patients (mean age, 64.1 years; male 75.7%) with stroke and hypertriglyceridemia (defined as fasting serum triglycerides levels of ≥ 150 mg/dL) who were treated with pemafibrate at 0.2 mg or 0.1 mg/day. The present report assessed the association of hypertriglyceridemia with cerebral large and small vessel diseases at baseline and changes in laboratory parameters after a three-month pemafibrate therapy.

Results: Patients with triglycerides levels of ≥ 227 mg/dL (higher than the median) more often presented with intracranial artery atherosclerotic stenosis than those with triglycerides levels of 150-227 mg/dL (44.4% vs. 21.6%, p=0.037). On the other hand, no differences were found in the prevalence of extracranial artery atherosclerosis and cerebral small vessel diseases. Mean triglycerides levels were significantly reduced from 285 mg/dL at baseline to 175 mg/dL at 3 months (p<0.001). High-density lipoprotein cholesterol levels increased from 48 mg/dL to 53 mg/dL (p<0.001). In addition, significant reductions in alanine aminotransferase, γ-glutamyl transpeptidase, and interleukin-6 levels were observed (p<0.001, p=0.002, and p=0.044, respectively).

Conclusions: Higher triglycerides levels are associated with intracranial artery atherosclerosis. Pemafibrate showed pleiotropic effects not only in ameliorating atherogenic dyslipidemia but also in the reduction of the levels of inflammatory markers and hepatobiliary enzymes.

Keywords: Anti-inflammatory; Cerebrovascular disease; Pemafibrate; Peroxisome proliferator-activated receptor alpha (PPARα); Triglycerides.

MeSH terms

  • Atherosclerosis* / complications
  • Benzoxazoles
  • Butyrates
  • Cerebral Arterial Diseases* / complications
  • Humans
  • Hyperlipidemias* / complications
  • Hypertriglyceridemia* / complications
  • Hypertriglyceridemia* / drug therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • Stroke* / drug therapy
  • Stroke* / prevention & control
  • Triglycerides

Substances

  • (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
  • Benzoxazoles
  • Butyrates
  • Triglycerides