Clinical trials with a statin or any other single intervention in patients with high CVD risk, including the presence of dia- betes mellitus, are often insufficiently powered to determine an effect on incident stroke. In 2008, data from 18686 indi- viduals with diabetes mellitus (1466 with type 1 and 17220 with type 2 diabetes mellitus) were assessed to determine the impact of a 1.0-mmol/l ( 40-mg/dL) reduction in LDL choles- During a mean follow-up of 4.3 years, there were 3247 major cardiovascular events with a 9% proportional reduction Meschia et al Guidelines for the Primary Prevention of Stroke 3771 in all-cause mortality per 1-mmol/L LDL cholesterol reduction were also reductions in MI or coronary death (RR, 0.78; 95% 0.93; P=0.0002). A subgroup analysis was carried out from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) in which subjects received either gemfibrozil (1200 mg/d) or placebo for 5.1 years.318 Compared with those with normal fasting plasma glucose, the risk for major cardiovascular events was higher in subjects with either mellitus. Gemfibrozil treatment did not affect the risk of stroke among subjects without diabetes mellitus, but treatment was associated with a 40% reduction in stroke in those with diabe- tes mellitus (HR, 0.60; 95% CI, 0.37 0.99; P= 0.046). The FIELD study assessed the effect of fenofibrate on car- diovascular events in 9795 subjects 50 to 75 years of age with type 2 diabetes mellitus who were not taking a statin therapy at study entry.319 The study population included 2131 people with and 7664 people without previous CVD. Over 5 years, 5.9% of patients (n=288) on placebo and 5.2% (n=256) on fenofibrate had a coronary event (P=0.16). There was a 24% MI. There was no effect on stroke with fenofibrate. 