Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function
Pharmacologic Effects of Antagonists on the Renin-Angiotensin-Aldosterone System
Despite standard therapy, patients with stable ischemic heart disease and preserved left ventricular systolic function continue to be at risk for future cardiovascular events. The Renin-Angiotensin-Aldosterone System (RAAS) is critical for regulating blood pressure, electrolyte balance, and fluid volume homeostasis and plays a pivotal role in the pathogenesis of hypertension, congestive heart failure, and diabetic nephropathy. Pharmacological antagonists of this system include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). These drugs block adverse effects of the RAAS by blocking the activity of angiotensin II. Through the stimulation of angiotensin II type-1 receptors, angiotensin II may have several potentially harmful activities including:
- Induction of aldosterone production, which can cause sodium retention and increased fluid retention that, in turn, leads to an increase in blood pressure.
- Increased aldosterone production, which can possibly lead to promotion of pathogenic remodeling (i.e., atherosclerosis and fibrosis).
- Constriction of blood vessels, which can lead to increased blood pressure.
- Potential reduction in the availability of nitric oxide through the production of free radicals and the induction of endothelial dysfunction that may impact endothelial wall integrity.
ACEIs act on the RAAS by blocking the conversion of angiotensin I into angiotensin II and inhibiting the breakdown of bradykinin, which is a potent vasodilator.
ARBs block the angiotensin II type-1 receptor and reduce the pharmacologic effects of angiotensin II, regardless of whether angiotensin II is created by the angiotensin-converting enzyme or by pathways that do not include this enzyme.
ACEIs and ARBs may potentially provide several pharmacological effects over and above that of blood pressure reduction alone, which may impact cardiovascular events.
- Ceconi C, Fox KM, Remme WJ, et al, for the EUROPA Investigators and the PERTINENT Investigators and the Statistical Committee. ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT. Cardiovasc Res 2007;73:237-46.
- Faxon DP, Fuster V, Libby P, et al, for the American Heart Association. Atherosclerotic Vascular Disease Conference: Writing Group III: pathophysiology. Circulation 2004;109:2617-25.
- Schmidt-Ott KM, Kagiyama S, Philips I. The multiple actions of angiotensin II in atherosclerosis. Regul Pept 2000;93:65-77.
- Song JC, White CM. Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor blockers. Pharmacotherapy 2000;20:130-9.
- Song JC, White CM. Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin-converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41:207-24.
- Coleman CI, Baker WL, Kluger J, et al. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II-Receptor Blockers Added to Standard Medical Therapy for Treating Stable Ischemic Heart Disease. Comparative Effectiveness Review No. 18. (Prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center under Contract No. 290-2007-10067-I.) Rockville, MD: Agency for Healthcare Research and Quality; October 2009.
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