The original Heart Outcomes Prevention Evaluation study (HOPE) demonstrated that the angiotensin-converting enzyme (ACE) inhibitor, ramipril, reduced the 3-part composite end point of cardiovascular death, myocardial infarction, and stroke by 22% in patients at high cardiovascular risk. Almost 10 years later, the angiotensin receptor blocker, telmisartan, in Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) produced a somewhat smaller but still significant 13% reduction in the same composite end point. The formal primary end point of TRANSCEND actually was composed of the HOPE triad plus hospitalized heart failure, but since the effects of telmisartan in preventing de novo heart failure did not differ from placebo, its effects on this expanded end point were diluted and so did not reach significance. The small modification in effect size by the treatment in TRANSCEND as compared with HOPE almost certainly reflects changes in the characteristics of the study population and their underlying therapies in the 10-year interval between these studies. The decision to include heart failure in the composite end point of TRANSCEND had a confounding rather than a helpful effect in understanding the cardiovascular protective effects of an angiotensin receptor blocker in a nonhypertension study. Despite this, the closely similar outcomes produced by ramipril and telmisartan in the definitive Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) confirm the consistency of the HOPE and TRANSCEND findings and, in particular, the value of a well-tolerated angiotensin receptor blocker like telmisartan as an alternative to ramipril in patients at high cardiovascular risk.