The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial randomized 2539 patients with type 2 diabetes mellitus but without a history of atheroscle- rotic disease (including stroke) to either low-dose aspirin (81 or 100 mg/d) or no aspirin.321 The primary outcome was the occur- rence of atherosclerotic events (fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease). There was no effect of aspirin on the primary end point (HR, 0.80; 95% CI, 0.58 1.10; P=0.16) and no effect on cerebrovas- cular events (2.2% with aspirin versus 2.5% with no aspirin; HR, 0.84; 95% CI, 0.53 1.32; P=0.44). There was no difference in the combined rates of hemorrhagic stroke and severe gastro- intestinal bleeding. A subgroup analysis of the JPAD trial noted that aspirin therapy lowered the rate of cerebrovascular events in patients with diabetes mellitus with uncontrolled hyperten- sion (SBP 140 mmHg and/or DBP 90 mmHg) compared with those with controlled BP (HR, 1.64; 95% CI, 0.83 3.29), although the 95% CI includes the possibility of no benefit.882 The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial was a randomized, double-blind, Meschia et al Guidelines for the Primary Prevention of Stroke 3797 placebo-controlled trial including 1276 adults with type 1 or 2 diabetes mellitus and an ankle-brachial index of 0.99 but no symptomatic CVD who were randomized in a 2-by-2 factorial design to 100 mg aspirin or placebo plus antioxidants or placebo The study had 2 primary end points: (1) death resulting from coronary heart disease or stroke, nonfatal MI or stroke, or amputation above the ankle for critical limb ischemia and (2) death resulting from coronary heart disease or stroke. There was no interaction between aspirin and antioxidant. 