Clinical trial update: focus on the ONTARGET study

The renin angiotensin system (RAAS) plays an important role in the pathophysiology of cardiovascular (CV) disease. Modulation of RAAS with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and aldosterone inhibitors reduces a range of adverse CV outcomes in patients with or at risk of CV disease. Currently, there is incomplete evidence to show all RAAS modulators provide vascular protection by reducing the incidence of myocardial infarction (MI), stroke and CV death. In patients at high risk for CV events, studies with ACEi designed to test for long-term vascular protection, showed benefit. In contrast, studies of ARBs in patients with hypertension, heart failure, and renal disease have not consistently shown a reduction of CV outcomes. However, none of these studies was specifically designed to examine the impact of ARBs on the vascular protective outcomes of CV death, non-fatal MI, and stroke. The ONTARGET and TRANSCEND studies are designed to determine whether the ARB telmisartan is similar (or non-inferior) or superior to the ACEi ramipril in the reduction of CV events in patients with established CV disease or diabetes with target organ damage. The ONTARGET study has enrolled 25,620, and TRANSCEND 5,776 subjects. The subjects in both trials are similar to those studied in the HOPE study, yet there is greater ethnic diversity, a higher proportion of patients with cerebro-vascular disease, and a greater use of beta blockers and lipid-lowering treatment. The studies completed recruitment in 2004, and are due to complete follow-up and report the results in 2008. The ONTARGET and TRANSCEND studies will provide valuable comparative data on the efficacy of telmisartan and ramipril and their combination in patients at high risk for CV events. Although it is possible that enhanced benefits will be observed with dual therapy, the outcomes with ARB monotherapy remain uncertain.