(Circulation. 1996;94:258-265.)
© 1996 American Heart Association, Inc.
Articles |
Angiotensin-Converting Enzyme Inhibition With Quinapril Improves Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
The TREND (Trial on Reversing ENdothelial Dysfunction) Study
the University of British Columbia, Vancouver, British Columbia, Canada (G.B.J.M.); Parke-Davis Pharmaceutical Research, Ann Arbor, Mich (G.C.H., M.I.K., H.E.H., A.C.G.U.); Hospital Clinico Universitaro, Madrid, Spain (C.M.); Dalhousie University, Halifax, Nova Scotia, Canada (B.J.O.); Westchester County Medical Center, Valhalla, NY (A.L.P.); St Paul's Hospital, Vancouver, British Columbia, Canada (R.G.C.); University of Florida, Gainesville (T.J.W., C.J.P.); Klinikum Innenstadt der Universitat, Munchen, Germany (H.M.); Inselspital Bern, Switzerland (T.F.L.); and University of Michigan, Ann Arbor (B.P.).
Background Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized.
Methods and Results Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n=54) and quinapril (n=51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5±3.0% [mean±SEM] versus -0.1±2.8% at 10-6 mol/L and 12.1±3.0% versus -0.8±2.9% at 10-4 mol/L, quinapril versus placebo, respectively; overall P=.002).
Conclusions TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.
Key Words: angiotensin • coronary disease • endothelium-derived factors • acetylcholine
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