TRENDS IN PHARMACY AND PHARMACEUTICAL CARE
An ongoing CE program of
The University of Mississippi School of Pharmacy and DRUG TOPS
Cardiovascular disease (CVD) remains the leading cause of death in the United States. Activation of the reninangiotensin system (RAS) plays a central role in the development and progression of CVD with the deleterious effects of angiotensin II increasingly being recognized. Disruption of the RAS offers considerable promise for treatment as well as prevention of cardiovascular disorders, including protection against the vascular and cardiac structural changes that precipitate adverse events. Angiotensin-converting enzyme (ACE) inhibitors were initially developed for use in the management of hypertension. Since the introduction of these agents for hypertension management, clinical trials have demonstrated quite conclusively that ACE inhibitors provide important advantages for preventing CVD progression. ACE inhibitors have received additional clinical indications and have become the treatment standard for several disease states. The beneficial effect of RAS blockage with ACE inhibitors is well recognized in the areas of heart failure; myocardial infarction; renal disease; and, most recently, stroke. ACE inhibitors decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. ACE inhibitors also delay the progression of renal disease, including diabetic nephropathy, and reduce the risk of stroke as well as the degree of functional impairment post-stroke. Results from the landmark Heart Outcomes Prevention Evaluation (HOPE) study have changed widespread views about how hypertension and those at risk for CVD should be treated.
The use of ACE inhibitors for CVD management and comparisons with angiotensin receptor blockers have been explored in earlier issues. The focus of this article will be on the expanding knowledge of the RAS, current understanding of the endothelium and endothelial dysfunction in CVD pathogenesis, and emerging roles for ACE inhibitors for primary prevention of CVD. Expanding knowledge of the HAS Beginning with the discovery of renin in 1898, the characterization and differentiation of the RAS has evolved over the past 100 years. The finding that Bothrops jararaca (Brazilian pit viper) venom peptides preserve or potentiate the effects of bradykinin was followed by the development of synthetic peptides and then the first orally active ACE inhibitors almost 25 years ago. An explosion in CVD research has accompanied these advances in RAS understanding. More has been learned about the RAS in the last decade than in the preceding 90 years.
Initial research efforts with ACE inhibitors focused on their use in hypertension, but they quickly expanded to heart failure; diabetes; and, most recently, stroke prevention. Since the introduction of captopril, with approval only for severe hypertension unresponsive to other agents, a remarkable turnabout has occurred. The benefits of ACE inhibitors have been confirmed in many largescale randomized clinical trials. ACE inhibitors are now included among the medications recommended for initial monotherapy for hypertension by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) for patients with a variety of comorbid conditions.
As the role of ACE inhibitors has developed in clinical use, special benefits beyond those provided by other agents have been recognized. It has also been importantly recognized that correcting blood pressure alone is not sufficient for CVD risk reduction. The strategy prescribed should also have the potential to prevent later cardiovascular morbid events, including heart failure, kidney failure, or stroke that shortens the useful life of a person with hypertension. The benefits of ACE inhibitors are clear in the relieving of acute and chronic heart failure, the preventing of remodeling and progressive ventricular dysfunction after myocardial infarction, and the slowing of glomerular sclerosis in diabetic and other nephropathies. …