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. There was no effect of aspirin on the composite primary end points (HR, 0.98; 95% CI, 0.76 1.26; P=0.86) or on death resulting from coronary heart disease or stroke (HR, 1.23; 95% CI, 0.79 1.93; P=0.36). There was no effect of aspirin on fatal stroke (HR, in the risk of gastrointestinal hemorrhage (HR, 0.90; 95% CI, 0.53 1.52; P=0.69). The lack of increased bleeding risk with aspirin in those with diabetes mellitus was also found in the observational study cited above (incidence rate ratio for aspirin Diabetes mellitus was independently associated with an increased risk of major bleeding regardless of aspirin use (RR, 1.36; 95% CI, 1.28 1.44). 