Cardiovascular protection: a breakthrough for high-risk patients

Blockade of the renin–angiotensin system (RAS) with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARBs) has been shown to reduce cardiovascular mortality and morbidity in various patient populations. The recent ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) studies with the ARB telmisartan, the largest outcome trial programme with an ARB, have extended this evidence base in the broadest cross section of cardiovascular high-risk patients, and provided important new insights into the benefits of RAS blockade. ONTARGET and TRANSCEND recruited patients who were at high risk of vascular events. These patients, who did not have established heart failure and had well controlled blood pressure, had not previously been studied in clinical trials with ARBs. Telmisartan provided cardiovascular protection similar to ramipril but was better tolerated. These studies add to the growing evidence that the effects of RAS inhibitors are not solely dependent on blood pressure reduction. Angiotensin II exerts diverse pro-atherosclerotic effects, and hence blockade of the RAS may directly inhibit the development and progression of atherosclerosis. Finally, together with other smaller outcomes studies, ONTARGET and TRANSCEND provide useful insights into the relative importance of hypertension and other risk factors at different stages of the ‘cardiovascular continuum’. The evidence suggests that high blood pressure has a major impact on cardiovascular risk in the early stages of the continuum, whereas other risk factors like RAS activation become progressively important in later stages.