Effects of Pemafibrate on Cardio-Ankle Vascular Index (CAVI) in Patients with Type 2 Diabetes or Ischemic Heart Disease: A 24-Week Observational Study

Yasuhiro Watanabe,1 Shoya Nonaka,2 Shuhei Yamaoka,1 Shoko Nakamura,1 Osamu Horikawa,1 Takashi Yamaguchi,1 Shuji Sato,2 Shunsuke Todani,2 Yuta Sugizaki,2 Takuro Ito,2 Hiroshi Mikamo,2 Mao Takahashi,2 Daiji Nagayama,3 Kazuhiro Shimizu,1 Atsuhito Saiki1 1Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, Chiba, Japan; 2Division of Cardiology, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan; 3Nagayama Clinic, Tochigi, JapanCorrespondence: Yasuhiro Watanabe, Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-City, Chiba, 285-8741, Japan, Tel +81-43-462-8811, Fax +81-43-462-8820, Email [email protected]: Pemafibrate is a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) that improves lipid profile, but its effects on cardiovascular events remain unproven. This study examined changes in the cardio-ankle vascular index (CAVI), a marker of arterial stiffness, in high-risk patients with type 2 diabetes mellitus (T2DM) or ischemic heart disease (IHD) treated with pemafibrate.Patients and Methods: In this single-center, prospective, observational study, 95 patients with T2DM and/or IHD, who had hypertriglyceridemia (≥ 150 mg/dL) and started pemafibrate (0.2 mg/day) were analyzed. CAVI was measured at baseline and after 24 weeks of treatment as an indicator of arterial stiffness, along with comprehensive assessment of lipid parameters including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and apolipoproteins.Results: No significant change in CAVI was observed after 24 weeks of treatment (median [interquartile range (IQR)]; baseline vs 24 weeks: CAVI 9.4 [8.8– 10.6] vs 9.6 [8.9– 10.8], p=0.715). However, pemafibrate significantly reduced triglycerides (233 mg/dL [171– 329] to 143 mg/dL [111– 187], p< 0.001), apolipoprotein C-II (8.1 mg/dL [6.1– 10.2] to 6.3 mg/dL [5.3– 8.3], p< 0.001), apolipoprotein C-III (15.3 mg/dL [12.2– 18.3] to 11.6 mg/dL [9.3– 14.2], p< 0.001) and liver enzymes; and increased HDL-C (45 mg/dL [39– 52] to 50 mg/dL [40– 60], p< 0.001), LDL-C (92 mg/dL [70– 111] to 103 mg/dL [79– 128], p< 0.001), apolipoprotein A-I and apolipoprotein A-II (both p< 0.05). Calculated small dense low-density lipoprotein cholesterol also decreased significantly (40 mg/dL [31– 49] to 36 mg/dL [28– 45], p=0.002).Conclusion: While pemafibrate improves lipid profile and liver enzymes, its short-term impact on vascular stiffness, as measured by CAVI, appears limited. Extended follow-up studies are needed to clarify its cardiovascular benefits in high-risk patients.Keywords: pemafibrate, cardio-ankle vascular index, CAVI, type 2 diabetes mellitus, hypertriglyceridemia