The effects on major clinical events of ARBs in patients without HF have been evaluated in several trials reporting conflicting results ((17),(18),(20),(21),(22),(23),(24),(25),(26),(27),(28),29). In the RENAAL (Reduction in ENdpoints with the Angiotensin Antagonist Losartan) study (21), losartan, compared with placebo, failed to reduce the secondary composite CV outcome, including CV death, MI, stroke, coronary or peripheral revascularization, and new HF, in diabetic patients with nephropathy. Similarly, in high-risk diabetic patients without (20) and with (22) overt nephropathy, irbesartan did not reduce CV events. In the SCOPE (Study on Cognition and Prognosis in the Elderly) (24), a candesartan-based therapy in hypertensive elderly patients failed to reduce the primary composite outcome of CV death, MI, and stroke, whereas it significantly decreased the risk of new-onset DM. In contrast, in a small study enrolling high-risk patients (23), candesartan, compared with placebo, significantly reduced the risk of a composite outcome including CV death, MI, and coronary revascularization. Subsequently, however, high-dose candesartan did not reduce CV events in patients with type 1 or type 2 DM with no previous CV events ((17),18). In the TRANSCEND (Telmisartan Randomised AssessmeNT Study in ACEiNtoleran subjects with cardiovascular Disease) trial (27), ACE-I–intolerant patients were enrolled and assigned to either telmisartan or placebo. Although the primary endpoint of CV death, MI, stroke, and new-onset HF was not significantly reduced by telmisartan, a 13% reduction in the secondary combined endpoint, including CV death, MI, and stroke was reported (p = 0.05), whereas new-onset DM was not reduced by telmisartan. However, in the PROFESS (Prevention Regimen For Effectively Avoiding Second Strokes) study (26), which enrolled patients with a recent stroke, telmisartan, compared with placebo, failed to reduce the recurrence of stroke, all-cause mortality, DM, or any CV endpoint. More recently, in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial (28), which enrolled stable patients with impaired glucose tolerance with or at high risk of developing CV disease, valsartan reduced the occurrence of DM but failed to reduce CV morbidity or mortality. Finally, the recently concluded ROADMAP (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention) (29) trial and the ORIENT (Olmesartan Reducing Incidence of End stage renal disease in diabetic Nephropathy Trial) (25) trial reported an increase of the prespecified secondary endpoint of CV mortality in diabetic patients receiving olmesartan, despite a favorable effect on the primary renal endpoint.