Primary prevention of cardiovascular diseases among hypercholesterolemic Japanese with a low dose of pravastatin.

The MEGA Study was Japan's first primary prevention trial of cardiovascular disease (CVD) by cholesterol lowering with low-dose pravastatin. Included were postmenopausal women aged < or =70 years and men aged 40-70 years with mildly elevated total cholesterol (TC) level 220-270 mg/dL. In all, 8214 outpatients were randomly assigned to receive diet alone or diet plus pravastatin 10-20mg/day for an average follow-up of 5.3 years. The primary endpoint was a composite of fatal and nonfatal MI, angina, cardiac and sudden death, and coronary revascularization. TC was reduced by 11.5% in the diet plus pravastatin group versus 2.1% in the diet alone group. LDL-C was reduced by 18% and 3.2% in the two groups, respectively. TC was reduced to <220 mg/dL and LDL-C to <130 mg/dL in patients in the diet plus pravastatin group. There was a significant 33% reduction of the primary endpoint in the diet plus pravastatin group compared with the diet alone group. Notable findings of the MEGA Study included the observation that despite pravastatin's modest LDL-C reductions in this low-risk population, a 33% reduction of CHD events was achieved. Even though 68% of patients were women, who have been traditionally considered at less risk than men, significant CHD risk reduction was observed across all groups.