Comparative assessment of angiotensin receptor blockers in different clinical settings

Abstract

Cardiovascular and renal disease can be regarded as progressing along a sort of continuum which starts with cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, etc), evolves with progression of atherosclerotic lesions and organ damage, and then becomes clinically manifest with the major clinical syndromes (myocardial infarction, stroke, heart failure, end-stage renal disease). The blood pressure control remains a fundamental mechanism for prevention of cardiovascular disease. The renin-angiotensin system is believed to play an important role along different steps of the cardiovascular disease continuum. Convincing evidence accumulated over the last decade that therapeutic intervention with angiotensin receptor blockers (ARBs) is effective to slow down or block the progression of cardiovascular disease at different steps of the continuum, with measurable clinical benefits. However, despite the shared mechanism of action, each ARB is characterized by specific pharmacological properties that may influence its clinical efficacy. Indeed, important differences among available ARBs emerged from clinical studies. Therefore, generalization of results obtained with a specific ARB to all available ARBs may be misleading. The present review provides a comparative assessment of the different ARBs in their efficacy on major clinical endpoints along the different steps of the cardiovascular disease continuum.

Keywords: eprosartan; hypertension; irbesartan; losartan; olmesartan; renin–angiotensin system; telmisartan; valsartan.

Figure 1

Cardiovascular disease continuum. Modified with permission from Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part ii: Clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation. 2006;114(25):2871–2891.

Figure 2

Major trials with angiotensin receptor blockers in specific cardiovascular conditions. Abbreviations: CHARM, Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity; ELITE, evaluation of Losartan in the elderly; I-PRESERVE, Irbesartan in Heart Failure with Preserved Ejection Fraction Study; IRMA, Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria; LIFE, Losartan intervention for End Point Reduction; ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; OPTIMAAL, Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan; RENAAL, Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan; SCOPE, Study on Cognition and Prognosis in the Elderly; VALIANT, Valsartan in Acute Myocardial infarction; Val-HEFT, Valsartan Heart Failure Trial; VALUE, Valsartan Antihypertensive Long-term Use Evaluation.

Figure 3

Effects on all-cause mortality in trials with ACE-inhibitors and in the VALIANT trial (with imputed placebo) in patients with myocardial infarction and evidence of heart failure or left ventricular dysfunction (hazard ratios and 95% confidence intervals). Copyright © 1999. Modified with permission from Mallion J, Siche J, Lacourciere Y. ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension. J Hum Hypertens. 1999;13(10):657–664. Abbreviations: SAVE, Survival and Ventricular Enlargement trial; TRACE, Trandolapril Cardiac Evaluation; AIRE, Acute Infarction Ramipril Efficacy trial.