Rationale and Design of the Cardiac Magnetic Resonance Imaging Substudy of the ONTARGET Trial Programme

Abstract

Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve cardiovascular disease outcomes in high-risk patients, but evidence for the cardioprotective effects of angiotensin II receptor blockers (ARBs) is less extensive. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the parallel Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) - which together form The ONTARGET Trial Programme – are long-term, large-scale, double-blind, multinational outcome studies with the primary objectives of determining if the combination of the ARB telmisartan 80 mg and the ACE inhibitor ramipril 10 mg is more effective than ramipril 10 mg alone, and if telmisartan is at least as effective as ramipril (in the case of ONTARGET), and if telmisartan is superior to placebo (in the case of TRANSCEND), in providing cardiovascular protection for high-risk patients. A pre-defined substudy is being conducted within The ONTARGET Trial Programme to compare the effects of these agents, alone and in combination, on cardiac structure and function. The substudy overcomes criticisms of many previous studies, which have been performed in small numbers of patients using suboptimal methodology, by evaluating changes in left ventricular structure and function using sophisticated technology provided by magnetic resonance imaging (MRI). Some 300 randomized patients within ONTARGET, recruited from selected centres in Australia, Canada, Germany, Hong Kong, New Zealand and Thailand, will have MRI undertaken at baseline and at 2-year follow-up. As this method of assessing left ventricular dysfunction is somewhat time-consuming, expensive and complex, and in the light of current interest in the role of B-type natriuretic peptide (BNP) as a simple, inexpensive diagnostic and prognostic tool, the substudy will also examine whether changes in BNP during follow-up correlated with changes in left ventricular dysfunction.