What is the role of ACE inhibitors in the treatment of coronary artery atherosclerosis?

Updated: Apr 09, 2021
  • Author: Sandy N Shah, DO, MBA, FACC, FACP, FACOI; Chief Editor: Yasmine S Ali, MD, MSCI, FACC, FACP  more...
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Answer

The efficacy of ACE inhibitors on CAD has been examined in blood pressure reduction studies and in studies of subjects with high risk factors for CAD.

ACE inhibitors are effective blood pressure–reducing agents and affect the heart and vasculature through direct and other mechanisms.

ACE inhibitors were not shown to affect plaque in a randomized angiographic regression study, the Quinapril Ischemic Event Trial (QUIET), of 463 subjects with CAD. [60]

B-mode ultrasonographic studies investigating plaque regression have provided confusing results at best. Although the second Prevention of Atherosclerosis with Ramipril Trial (PART 2) showed no reduction in intima-media thickness at 4-year follow-up in 617 subjects randomized to placebo or ramipril (5-10 mg/d), the Study to Evaluate Carotid Ultrasound Changes with Ramipril and Vitamin E (SECURE) showed a reduction in carotid intima-media thickness proportional to the dose of ramipril (2.5-10 mg/d) in 750 subjects over a 4.5-year follow-up period. [61]

ACE inhibitors probably affect endothelial function, as well as those of A-II and kinin, to elicit the clinical effects observed in the clinical trials. Tissue binding is variable among the ACE inhibitors, with the highest affinity shown by quinapril, benazepril, and ramipril. In the Trial on Reversing Endothelial Dysfunction (TREND), [62] which included 105 subjects with CAD (but without CHF or left ventricular dysfunction), the group receiving quinapril at 40 mg/d showed significantly improved response to acetylcholine. ACE inhibitors also increase levels of nitric oxide by increasing its release through a kinin-mediated pathway and through reduction of its breakdown.

Statin therapy decreases cardiovascular events and all-cause mortality in both women and men. [63]

In addition, ACE inhibitors decrease the plasma levels of type 1 plasminogen activator inhibitor, increase the release of tissue-type plasminogen activator, and favorably affect the fibrinolytic balance, an effect not observed with the angiotensin receptor–blocking agents.

In terms of blood pressure reduction, even though a greater stroke incidence was observed with higher baseline blood pressure in the treatment group in the Captopril Prevention Project (CAPPP), a pooled analysis of 16,161 patients from blood-pressure control trials evaluating ACE inhibitors showed no difference in the cardiovascular outcome risk. [64]

A possible direct effect of ACE inhibitors on atherosclerosis, independent of blood pressure reduction, was suggested by the Heart Outcomes Prevention Evaluation (HOPE) study, [65] which included 9297 subjects with history of CAD, stroke, peripheral vascular disease, or diabetes, along with one other CAD risk factor (eg, hypertension, hypercholesterolemia, hypoalphalipoproteinemia, tobacco abuse, microalbuminuria). Subjects were randomized to placebo or ramipril (10 mg/d). At 5-year follow-up, the cardiac death rate was reduced by 25%, nonfatal MI by 20%, need for bypass surgery/PTCA by 16%, and all-cause mortality by 16%. The effects were unrelated to the blood pressure–lowering effect.


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