Vascular effects of simvastatin combined with ramipril in hypercholesterolemic patients with coronary artery disease, compared with simvastatin alone: a randomized, double-blind, placebo-controlled, crossover study.
Because the mechanisms of the biological effects of statin and angiotensin converting enzyme inhibitor therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic patients with coronary artery disease. We administered simvastatin 20 mg and placebo or ramipril 10 mg daily during 2 months with washout 2 months to 32 hypercholesterolemic patients with coronary artery disease. This study was randomized, double-blind, placebo-controlled, crossover in design. Simvastatin alone or combined with ramipril significantly changed lipoproteins, and improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements by 33 +/- 6% and by 50 +/- 14%, respectively (both P <0.001) and reduced plasma levels of nitrate relative to baseline measurements (P=0.413 and 0.037, respectively), the plasma MDA levels relative to baseline measurements by 8 +/- 8% and by 18 +/- 9% (P=0.039 and P <0.001, respectively) and MCP-1 relative to baseline measurements by 7 +/- 4% and by 13 +/- 3%, respectively (P=0.019 and P <0.001, respectively), and CRP from 0.22 to 0.14 mg/dl and from 0.22 to 0.15 mg/dl, respectively (P=0.124 and 0.002, respectively), and PAI-1 antigen relative to baseline measurements (P=0.690 and 0.018, respectively). However, simvastatin combined with ramipril changed to greater but statistically insignificant extent the percent flow-mediated dilator response to hyperemia and plasma levels of nitrate, MDA, MCP-1, and PAI-1 antigen than simvastatin alone. Simvastatin alone or combined with ramipril showed significant beneficial effects on endothelial function in hypercholesterolemic patients with coronary artery disease. However, simvastatin combined with ramipril did not significantly change, compared with simvastatin alone.
kVascular Medicine and Atherosclerosis Unit, Cardiology, Gil Heart Center, Gachon Medical School, Kuwol-dong 1198, Namdong-gu, Incheon 405-760, Korea. kwangk@ghil.com
Kwang Kon
KK
Koh
Ji Won
JW
Son
Jeong Yeal
JY
Ahn
Dong Kyu
DK
Jin
Hyung Sik
HS
Kim
Dae Sung
DS
Kim
Seung Hwan
SH
Han
Wook-Jin
WJ
Chung
Gi Soo
GS
Park
Eak Kyun
EK
Shin
D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000008:administration & dosage*; D019821:Simvastatin / Q000008:administration & dosage*; D014666:Vasomotor System / Q000187:drug effects
D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D019821:Simvastatin; D017257:Ramipril