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Additive Beneficial Effects of Fenofibrate Combined With Candesartan in the Treatment of Hypertriglyceridemic Hypertensive Patients

¹ Department of Cardiology, Laboratory Medicine, Gachon Medical School, Incheon, Korea
² Diabetes Unit, Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland
³ Department of Statistics, Ewha Womans University, Seoul, Korea

Address correspondence and reprint requests to Kwang Kon Koh, MD, PhD, FACC, FAHA, Professor of Medicine, Director, Vascular Medicine and Atherosclerosis Unit, Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, Korea 405-760. E-mail: kwangk{at}gilhospital.com

OBJECTIVE—Mechanisms underlying fibric acid and angiotensin II type 1 receptor blocker therapies differ. Signaling from peroxisome proliferator-activated receptor may cross-talk with the angiotensin II system. We investigated vascular and metabolic responses to these therapies either alone or in combination in hypertriglyceridemic hypertensive patients.

RESEARCH DESIGN AND METHODS—This was a randomized, double-blind, placebo-controlled, cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-four patients were given 200 mg fenofibrate and placebo, 200 mg fenofibrate and 16 mg candesartan, or 16 mg candesartan and placebo daily during each treatment period.

RESULTS—Fenofibrate, combined therapy, or candesartan therapy significantly reduced blood pressure. However, combined therapy significantly reduced blood pressure more than fenofibrate or candesartan alone (P < 0.001 by ANOVA). When compared with candesartan, fenofibrate or combined therapy significantly improved the lipoprotein profile. All three treatment arms significantly improved flow-mediated dilator response to hyperemia. Combined therapy significantly decreased plasma malondialdehyde, high-sensitivity C-reactive protein, and soluble CD40L levels relative to baseline measurements. Importantly, these parameters were changed to a greater extent with combined therapy when compared with monotherapy (P < 0.001, P = 0.002, P = 0.050, and P = 0.032 by ANOVA, respectively). Fenofibrate, combined therapy, and candesartan significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. However, the magnitude of these increases were not significantly different among the three therapies (P = 0.246 and P = 0.153 by ANOVA, respectively).

CONCLUSIONS—Fenofibrate combined with candesartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy in hypertriglyceridemic hypertensive patients.

Abbreviations: ARB, angiotensin II type 1 receptor blocker • AT₁R, angiotensin II type 1 receptor • MDA, malondialdehyde • PPAR, peroxisome proliferator-activated receptor • QUICKI, quantitative insulin sensitivity check index

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