Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese - MEGA

Description:

The goal of the trial was to evaluate pravastatin therapy in addition to diet modification with diet modification alone among Japanese patients with hypercholesterolemia.

Study Design

Study Design:

Patients Enrolled: 7832
Mean Follow Up: Mean 5.3 years
Mean Patient Age: Mean age 58 years
Female: 68

Patient Populations:

Men age 40 to 70 years and postmenopausal women up to age 70 years with total cholesterol 220-270 mg/dL; weight ≥40 kg.

Exclusions:

Familial hypercholesterolemia; history of coronary heart disease, stroke, TIA, or cancer

Primary Endpoints:

Composite of coronary heart disease events, defined as cardiac and sudden death, fatal and nonfatal myocardial infarction (MI), angina, and cardiac or vascular intervention

Secondary Endpoints:

Stroke, CHD composite or cerebral infarction, any cardiovascular event, total mortality

Drug/Procedures Used:

The trial was conducted in Japan from 1994 through 1999. Patients were randomized to diet modification alone (n=3,966) or diet modification plus pravastatin (10-20 mg per day; n=3,866). Patients were followed for a mean of 5.3 years.

Principal Findings:

Baseline characteristics were well-balanced between groups, with mean BMI of 23.8 kg/m2, 21% diabetics, and 20% current/past smokers. Total cholesterol at baseline was 242.6 mg/dL, LDL was 157 mg/dL, HDL was 57.5 mg/dL, and triglycerides was 127 mg/dL. Total cholesterol was reduced by 11.5 mg/dL in the pravastatin group and by 2.1 mg/dL in the diet alone group. Likewise, the reduction in LDL was greater in the pravastatin group (-18.0 vs -3.2 mg/dL). HDL increased by 5.8 mg/dL in the pravastatin group and by 3.2 mg/dL in the diet alone group, while triglycerides were reduced by 3.1 mg/dL in the pravastatin group but increased by 1.3 mg/dL in the diet alone group.

The primary composite endpoint of coronary heart disease events occurred less frequently in the pravastatin plus diet group (3.3 vs 5.0 per 1000 patient years, hazard ratio [HR] 0.67, p=0.01). Total mortality was non-significantly lower in the pravastatin group (2.7 vs 3.8 per 1000 patient years, HR 0.72, p=0.055). MI occurred less often in the pravastatin group (0.9 vs 1.6 per 1000 patient years, p=0.03). There was no significant difference in stroke (2.5 vs 3.0 per 1000 patient years, p=0.33) or cerebral infarction plus TIA (2.0 vs 2.6 per 1000 patient years, p=0.23) but the composite of CHD event or cerebral infarction was lower in the pravastatin group (5.0 vs 7.1 per 1000 patient years, p=0.005). There was no difference in the frequency of cancer (6.0 vs 6.2 per 1000 patient years) or elevated liver function abnormalities (2.8% each) and no cases of rhabdomyolysis.

Interpretation:

Among Japanese patients with hypercholesterolemia, treatment with pravastatin therapy in addition to diet modification was associated with a reduction in the primary composite endpoint of coronary heart disease events compared with diet modification alone at a mean 5.3 year follow-up.

Previous studies conducted in Western populations have shown reductions in adverse coronary events associated with statin therapy use. However, the cardiac morbidity and mortality in Japan is much lower than in the US and other western countries where statin therapy has been predominantly studied. The present study demonstrated that even in this lower risk population, primary prevention with low-dose statin therapy can be effective in reducing cardiac events, with only a somewhat moderate reduction in lipid parameters.

References:

Nakamura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 2006; 368: 1155–63. Presented by Dr. Haruo Nakamura at the American Heart Association Scientific Session, Dallas, Texas, November 2005.

Clinical Topics: Dyslipidemia, Prevention, Vascular Medicine, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Coronary Artery Disease, Neoplasms, Follow-Up Studies, Pyridinolcarbamate, Hyperlipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Rhabdomyolysis, Cholesterol, Body Mass Index, Cerebral Infarction, Pravastatin, Liver, Diet, Diabetes Mellitus


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