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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

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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:

  1. Induction of aldosterone production, which can cause sodium retention and increased fluid retention that, in turn, leads to an increase in blood pressure.
  2. Increased aldosterone production, which can possibly lead to promotion of pathogenic remodeling (i.e., atherosclerosis and fibrosis).
  3. Constriction of blood vessels, which can lead to increased blood pressure.
  4. 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.