Effects of valsartan alone versus valsartan/simvastatin combination on ambulatory blood pressure, C-reactive protein, lipoproteins, and monocyte chemoattractant protein-1 in patients with hyperlipidemia and hypertension.
Angiotensin receptor blockers have been hypothesized to have synergistic effects with statins. We evaluated the effects of valsartan alone or combined with simvastatin on blood pressure (BP) and indexes of inflammation and oxidant stress in hypertensive patients with hyperlipidemia. In this double-blind trial, 404 patients were randomized to 12 weeks valsartan 160 mg (V) or valsartan 160 mg plus simvastatin 20 mg (V/S20) or 80 mg (V/S80). Twenty-four-hour mean ambulatory BP and biochemical marker measurements were recorded at baseline and study end. There were no statistically significant between-treatment differences for least-square mean reductions from baseline in systolic BP (V, -9.22; V/S20, -9.25; V/S80, -9.58 mm Hg; p <0.0001 for all within-treatment changes vs baseline). Plasma high-sensitivity C-reactive protein decreased with the combinations but not with V alone (least-square mean median change from baseline, -0.16, -0.20, -0.70 mg/L; p = 0.0001 for V/S80 vs baseline; p = 0.045 for V/S20 vs baseline; p = 0.0023 for V/S80 vs V/S20; p = 0.0045 for V/S80 vs V). Monocyte chemoattractant protein-1 was reduced by V, with no evidence for additional lowering with V/S combinations. In conclusion, addition of simvastatin to valsartan did not incrementally lower BP. However, V/S80 was superior to V and V/S20 in reducing high-sensitivity C-reactive protein.
Rajagopalan
Sanjay
S
Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA. sanjay.rajagopalan@osumc.edu
Zannad
Faiez
F
Radauceanu
Anca
A
Glazer
Robert
R
Jia
Yan
Y
Prescott
Margaret Forney
MF
Kariisa
Mbabazi
M
Pitt
Bertram
B
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D018660:Blood Pressure Monitoring, Ambulatory; D002097:C-Reactive Protein / Q000032:analysis*; D018932:Chemokine CCL2 / Q000097:blood*; D004311:Double-Blind Method; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
D000959:Antihypertensive Agents; D015415:Biomarkers; D018932:Chemokine CCL2; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D013777:Tetrazoles; D000068756:Valsartan; D002097:C-Reactive Protein; D019821:Simvastatin; D014633:Valine