Additive beneficial effects of fenofibrate combined with candesartan in the treatment of hypertriglyceridemic hypertensive patients.
OBJECTIVE
Mechanisms underlying fibric acid and angiotensin II type 1 receptor blocker therapies differ. Signaling from peroxisome proliferator-activated receptor alpha 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.


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.
Koh
Kwang Kon
KK
Department of Cardiology, Laboratory Medicine, Gachon Medical School, Incheon, Korea. kwangk@gilhospital.com
Quon
Michael J
MJ
Han
Seung Hwan
SH
Chung
Wook-Jin
WJ
Ahn
Jeong Yeal
JY
Kim
Jeong-A
JA
Lee
Yonghee
Y
Shin
Eak Kyun
EK
D052242:Adiponectin / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008074:Lipoproteins / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D012044:Regression Analysis; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014666:Vasomotor System / Q000187:drug effects
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D013777:Tetrazoles; D008315:Malondialdehyde; D002097:C-Reactive Protein; C081643:candesartan; D011345:Fenofibrate