ArticlesPrimary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial
Introduction
Several large-scale primary and secondary prevention trials1, 2, 3, 4, 5, 6, 7, 8, 9, 10 have reported that cholesterol-lowering therapy can reduce the rates of the first occurrence and recurrence of coronary heart disease by about 20–40%. However, little is known of the relation between decreasing cholesterol concentrations and risk reduction for coronary heart disease in Japan, since many of the trials were done in countries with higher incidences of coronary heart disease than those seen in Japan.11, 12 Whether the results of clinical studies done outside Asia can be extrapolated to Japanese patients with hypercholesterolaemia is not known because of the differences in lifestyle and the incidence of coronary heart disease and stroke between Japan and western countries (about a third lower and two times higher, respectively).
This prospective randomised controlled trial was designed to assess the primary preventive effect of a statin against coronary heart disease in daily clinical practice in Japan. The dose of pravastatin used in this study is consistent with the approved dose in Japan and lower than the doses used in previous large-scale clinical trials done in western populations. Thus, the results from this trial will provide valuable guidance about the future treatment of hypercholesterolaemia in Japan.
Section snippets
Patients
The details of this prospective randomised, open-labelled, blinded-endpoint13 study have been reported previously.14 Briefly, men and postmenopausal women aged 40–70 years with a bodyweight of 40 kg or more and hypercholesterolaemia (total cholesterol concentration 5·69–6·98 mmol/L) were eligible for study enrolment between February, 1994, and March, 1999. Major exclusion criteria were familial hypercholesterolaemia and a history of coronary heart disease or stroke. Other exclusion criteria
Results
Figure 1 shows the trial profile. Of 7832 patients who were analysed, 2223 consented and 1013 refused to extend follow-up. The remaining 4596 patients completed the study at 5 years. The baseline characteristics of the analysed patients are presented in table 1.
7730 (98·7%) study patients completed follow-up after 5 years or more, and no difference was seen in the number of patients followed in both groups. The follow-up period was 41 195 person-years (mean follow-up period 5·3 years). In the
Discussion
This study shows that low doses of pravastatin can reduce the risk of coronary heart disease in Japanese patients, despite only small to moderate reductions in total cholesterol and LDL-cholesterol concentrations. Thus, in low-risk populations—eg, hypercholesterolaemic Japanese patients with high HDL cholesterol—less aggressive cholesterol-lowering therapy might be sufficient to produce a substantial and beneficial risk reduction for the primary prevention of coronary heart disease.
This trial,
References (26)
- et al.
Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial
Lancet
(2002) - et al.
Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
Lancet
(2003) - et al.
Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial
Lancet
(2004) - et al.
Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia
N Engl J Med
(1995) - et al.
Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels
JAMA
(1998) Randomised trial of cholesterol lowering in 4444 participants with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
Lancet
(1994)- et al.
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels
N Engl J Med
(1996) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels
N Engl J Med
(1998)The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care
JAMA
(2002)- et al.
Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20 536 people with cerebrovascular disease or other high-risk conditions
Lancet
(2004)