No HOPE without proof: do ARBs meet the standard for cardiovascular protection?

Blockade of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) plays an important role in the protection and prevention of cardiovascular disease. The Heart Outcomes Prevention Evaluation (HOPE) study established the significant effect of ACE inhibition on cardiovascular morbidity and mortality beyond blood pressure control. Smaller studies have demonstrated the efficacy of ARBs. In addition, a recent analysis from the Blood Pressure Lowering Treatment Trialists' Collaboration showed that ARB-based and ACE inhibitor-based treatment regimens were comparable in terms of the odds ratio for stroke and heart failure, independent of blood pressure reduction. There is an emerging body of evidence to suggest that a combination approach to RAS blockade with an ARB and an ACE inhibitor may further improve cardiovascular outcome compared with monotherapy with either agent alone. The large-scale ONgoing Telmisartan Alone or in combination with Ramipril Global Endpoint Trial (ONTARGET), comparing high-dose ramipril (HOPE study dosage) with telmisartan or a combination of the two, should provide important insight into the benefits of RAS blockade intervention. The results of ONTARGET are anticipated to be available in 2008.