The Heart Outcomes Prevention Evaluation (HOPE) study compared the addition of an ACEI to the current medical regi- men in high-risk patients. The substudy of 3577 patients with diabetes mellitus with a previous cardiovascular event or an additional cardiovascular risk factor (total population, 9541 participants) showed a reduction in the ACEI group in the primary combined outcome of MI, stroke, and cardiovascular Whether these benefits repre- sent a specific effect of the ACEI or were simply the result of BP lowering remains unclear. The LIFE study compared the effects of an ARB with a -adrenergic receptor blocker in 9193 people with essential hypertension (160 200/95 115 mmHg) and electrocardiographically determined left ventricular hyper- BP reductions were similar for each group. The 2 regimens were compared among the subgroup of 1195 people who also had diabetes mellitus in a prespeci- There was a 24% reduction (RR, 0.76; 95% CI, 0.58 0.98) in major vascular events and a nonsignificant 21% reduction (RR, 0.79; 95% CI, 0.55 1.14) in stroke among those treated with the ARB. The ADVANCE Trial also determined whether a fixed combination of perindopril and indapamide or matching pla- cebo in 11140 patients with type 2 diabetes mellitus would decrease major macrovascular and microvascular events.307 After 4.3 years of follow-up, subjects assigned to the com- bination had a mean reduction in BP of 5.6/2.2 mmHg. The risk of a composite of major macrovascular and microvascu- lar events was reduced by 9% (HR, 0.91; 95% CI, 0.83 1.00; P=0.04), but there was no reduction in the incidence of major macrovascular events, including stroke. 