Journal Article

Efficacy and Safety of Fimasartan, Atorvastatin, and Ezetimibe Combination Therapy in Patients With Hypertension and Dyslipidemia: A Randomized, Double-Blind, Multicenter, Therapeutic Confirmatory, Phase III Clinical Trial

Cho, Deok-Kyu, Cho, Goo-Yeong, Kim, Ju Hyeon, Kim, Kye Hun, Cha, Tae-Joon, Cha, Kwang Soo, Lee, Sang-Yeub, Moon, Jae Youn, Yoon, Young Won, Yi, Jeong-Eun, Hahn, Joo-Yong, Sung, Ki-Chul, Ahn, Jong-Hwa, Cho, Yoon Haeng, Hong, Soon Jun, Son, Jang-Won, Lee, Jin Bae, Rhee, Moo-Yong, Shin, Jinho, Ahn, Kye Tack, Kang, Woong Chol, Jeong, Hyeonju, Park, Sang-Don, Lee, Jung-Hee, Park, Jong-Pil, Ha, Jong-Won

2025

Overview

•A fixed-dose triple combination of Fimasartan, atorvastatin, and ezetimibe (FAE) effectively controls both blood pressure and LDL-cholesterol simultaneously.•The safety profile of the FAE triple therapy is comparable to that of its individual components, confirming its tolerability.•The single-pill FAE combination may simplify treatment regimens for patients, potentially improving medication adherence.•This is the first phase III clinical trial to validate the efficacy and safety of the fixed-dose FAE combination therapy. Essential hypertension and primary hypercholesterolemia are common and independent cardiovascular risk factors that frequently coexist and warrant integrated management. This study aimed to evaluate the efficacy and safety of triple combination therapy (FMS + ATO/EZE) with Fimasartan (FMS), atorvastatin (ATV), and ezetimibe (EZE) compared with atorvastatin/ezetimibe (ATO/EZE) dual therapy or Fimasartan (FMS) monotherapy in patients with hypertension and hypercholesterolemia. This multicenter, randomized clinical trial was conducted across 25 clinical trial institutions in the Republic of Korea. A total of 315 participants were screened, of whom 148 eligible participants were randomized to receive FMS + ATO/EZE (n = 49), ATO/EZE (n = 49), or FMS (n = 50). The primary efficacy endpoints were the change in mean sitting systolic blood pressure (msSBP) from baseline to week 8 in the FMS + ATO/EZE group compared with that in the ATO/EZE group and the percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 8 in the FMS + ATO/EZE group compared with that in the FMS group. Safety was assessed based on treatment-emergent adverse events (TEAEs). In the full analysis set, the FMS + ATO/EZE group demonstrated superior reduction in msSBP compared to the ATO/EZE group (least squares [LS] mean difference: –7.26 ± 2.84 mm Hg; 95% confidence interval [CI]: –12.91, –1.61; P = 0.0124). Similarly, the percentage reduction in LDL-C was significantly greater in the FMS + ATO/EZE group than in the FMS group (LS mean difference: –58.02% ± 4.03%; 95% CI: –66.03, –50.02; P < 0.0001). The incidence of TEAEs was comparable across treatment groups: FMS + ATO/EZE (20.83%), ATO/EZE (22.45%), and FMS (16.00%) (P = 0.7030). Serious adverse events occurred in 1.36% of the total safety population, without significant difference between the groups (P = 0.5480). Triple combination therapy with FMS + ATO/EZE was superior to dual therapy or monotherapy in reducing both BP and LDL-C levels in patients with essential hypertension accompanied by primary hypercholesterolemia. The safety profile was comparable with that of the individual components, confirming the tolerability and safety of FMS + ATO/EZE therapy. However, the 8-week follow-up period and enrollment of an exclusively Korean cohort may limit the assessment of long-term effects and generalizability to other ethnic populations.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adverse events / Aged / Anticholesteremic Agents - administration & dosage / Anticholesteremic Agents - adverse effects / Anticholesteremic Agents - therapeutic use / Antihypertensive Agents - administration & dosage / Antihypertensive Agents - adverse effects / Antihypertensive Agents - therapeutic use / Antihypertensives / Atorvastatin / Atorvastatin - administration & dosage / Atorvastatin - adverse effects / Atorvastatin - therapeutic use / Azetidines - administration & dosage / Azetidines - adverse effects / Azetidines - therapeutic use / Biphenyl Compounds - administration & dosage / Biphenyl Compounds - adverse effects / Biphenyl Compounds - therapeutic use / Blood pressure / Blood Pressure - drug effects / Cardiovascular diseases / Cholesterol / Cholesterol, LDL - blood / Clinical trials / Combination therapy / Double-Blind Method / Drug Therapy, Combination / Dyslipidemia / Essential hypertension / Ezetimibe / Ezetimibe - adverse effects / Ezetimibe - therapeutic use / Female / Fimasartan / High density lipoprotein / Humans / Hypercholesterolemia / Hypercholesterolemia - complications / Hypercholesterolemia - drug therapy / Hypertension / Hypertension - complications / Hypertension - drug therapy / Internal Medicine / Laboratories / Lipids / Long-term effects / Low density lipoprotein / Male / Metabolic disorders / Middle Aged / Patient safety / Patients / Primary hypercholesterolemia / Pyrimidines - administration & dosage / Pyrimidines - adverse effects / Pyrimidines - therapeutic use / Republic of Korea / Risk factors / Safety / Sample size / Self-efficacy / Statins / Tetrazoles - administration & dosage / Tetrazoles - adverse effects / Tetrazoles - therapeutic use / Treatment Outcome / Triple combination therapy