Angiotensin II antagonists--therapeutic benefits spanning the cardiovascular disease continuum from hypertension to heart failure and diabetic nephropathy.

BACKGROUND

The cardiovascular benefits of angiotensin II antagonists (AIIAs) have been evaluated not only in terms of their ability to lower blood pressure but also on their ability to prevent strokes, cardiac events, and target organ damage. This review summarizes the body of evidence-based data demonstrating the efficacy of AIIAs across the spectrum of cardiovascular disease.

METHODS

A PubMed/MEDLINE search of English-language articles (1990 to September 2005) was used to identify articles describing clinical studies, particularly outcome trials, or mechanisms of therapeutic action pertinent to the therapy of cardiovascular disease or nephropathy.

FINDINGS

The antihypertensive efficacy of AIIAs is apparent across a wide spectrum of hypertensive patients, including black and Asian patients and patients with isolated systolic hypertension. More importantly, large outcome-based studies have demonstrated the efficacy of AIIAs across the continuum of cardiovascular disease, including hypertension, heart failure, post-myocardial infarction, and diabetic nephropathy. The Losartan Intervention For Endpoint reduction in hypertension study (LIFE), Reduction of Endpoints in Non-insulin-dependent Diabetes Mellitus with the AII Antagonist Losartan (RENAAL), and the Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT) indicate that AIIAs confer cardiovascular and renal protective effects beyond their ability to lower blood pressure. These bloodpressure independent protective benefits of AIIAs may arise not only by blocking the deleterious effects of AII mediated via the AT1-receptor but may also be due to beneficial molecule-specific effects. As a class, AIIAs are well tolerated with an overall adverse event profile generally comparable to placebo and superior to that typically seen with calcium channel blockers, ACE inhibitors, diuretics, and beta-blockers.

CONCLUSIONS

By utilizing the body of clinical trial evidence as a guide to rational prescribing of AIIAs, practitioners can expect to deliver clinical benefits to their patients in terms of survival, prognosis, and quality of life.