Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients.
BACKGROUND
Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients.


RESULTS
This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both P<0.001 and P=0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.001 for adiponectin, P=0.029 for QUICKI by ANOVA).


CONCLUSIONS
Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.
Koh
Kwang Kon
KK
Cardiology, Vascular Medicine and Atherosclerosis Unit,Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, Korea. kwangk@ghil.com
Quon
Michael J
MJ
Han
Seung Hwan
SH
Chung
Wook-Jin
WJ
Ahn
Jeong Yeal
JY
Seo
Yiel-Hea
YH
Kang
Moon Ho
MH
Ahn
Tae Hoon
TH
Choi
In Suck
IS
Shin
Eak Kyun
EK
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008055:Lipids / Q000097:blood; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D008315:Malondialdehyde; D002097:C-Reactive Protein; D019821:Simvastatin; D019808:Losartan