September 28, 2006 (Tokyo, Japan) – Results of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study, the first large-scale primary-prevention trial in a Japanese population that showed statin therapy reduces the risk of coronary heart disease (CHD), have now been published in the September 30, 2006 issue of the Lancet.
MEGA, first presented by lead author
Dr Haruo Nakamura (National Defense Medical College, Saitama, Japan) at the
American Heart Association Scientific (AHA)
Sessions 2005 in Dallas, TX, showed that the addition of
pravastatin 10 mg to a low-fat diet rich in omega-3 fatty acids reduces the risk of CHD in Japanese individuals with moderately elevated cholesterol levels by 33%, approximately the same reduction observed in US and European primary-prevention trials that have used larger statin doses.
In an editorial accompanying the published paper,
Drs Cesare Sirtori and
Laura Calabresi (University of Milan, Italy) said the MEGA trial answers important questions at a time of widened indications for statin use, particularly among low-risk populations such as the Japanese, in whom the need for cholesterol-lowering drugs might be overstated. Moreover, the study emphasizes the importance of population vs individual approaches, they write, as well as highlights the importance of calculating an absolute rather than relative-risk reduction. As noted during the AHA presentation, the absolute benefit was small--a little over a 1% absolute reduction in risk--and the number needed to treat to prevent one additional CHD event was 119.
"MEGA provides an important lesson at a time of wide availability of over-the-counter statins in the UK, as well as generic statins in the USA," they write. "The low population benefit of statins in MEGA, the consequent number needed to treat of 119, and the apparently limited benefit in women probably do not justify a publicly supported distribution of statins--but might, however, encourage direct access by patients to statins."
While widened access should not eliminate the supervision of patients by doctors, especially as statins might lead to muscle symptoms or myopathy, the MEGA findings, write Sirtori and Calabresi, assure clinicians that statins are effective in low-risk individuals and do not cause excess noncardiovascular deaths. The editorialists point out that the risk reduction occurred despite relatively modest reductions in total and LDL cholesterol and that the benefit was observed in patients with and without diabetes, in those who smoked, and in those who were overweight.
Primary prevention in a low-risk Asian population
Briefly, the MEGA study was a prospective, randomized, open-label trial comparing diet, one low in total cholesterol and saturated fat and including at least three servings of fish per week, plus pravastatin 10 mg with diet alone for the reduction of first-occurrence CHD in 7832 patients without a previous history of heart disease or stroke. Among those treated with statins, nearly 25% were treated with pravastatin 20 mg.
Average baseline LDL-cholesterol levels were 156 mg/dL in both study arms before treatment. During a mean follow-up of 5.3 years, treatment with pravastatin 10 mg significantly decreased total- and LDL-cholesterol levels 11.5% and 18%, respectively.
Briefly, the MEGA study was a prospective, randomized, open-label trial comparing diet, one low in total cholesterol and saturated fat and including at least three servings of fish per week, plus pravastatin 10 mg with diet alone for the reduction of first-occurrence CHD in 7832 patients without a previous history of heart disease or stroke. Among those treated with statins, nearly 25% were treated with pravastatin 20 mg.
Average baseline LDL-cholesterol levels were 156 mg/dL in both study arms before treatment. During a mean follow-up of 5.3 years, treatment with pravastatin 10 mg significantly decreased total- and LDL-cholesterol levels 11.5% and 18%, respectively.
The MEGA investigators report that treatment with pravastatin reduced the risk of CHD 33% compared with patients randomized to diet alone, driven by reductions in MI and coronary revascularization. The results were even better in patients older than 60 years and in those with LDL cholesterol levels
>155 mg/dL. There was no reduction in the risk of stroke and no increased risk of death from noncardiovascular causes.
Risk of primary and secondary end points in MEGA
|
End point
|
Hazard ratio (95% CI)
|
|
Coronary heart disease (primary)
|
0.67 (0.49–0.91)
|
|
0.52 (0.29–0.94)
|
|
0.51 (0.18–1.50)
|
|
0.83 (0.56–1.23)
|
|
0.60 (0.41–0.89)
|
|
Stroke
|
0.83 (0.57–1.21)
|
|
All cardiovascular events
|
0.74 (0.59–0.94)
|
|
Total mortality
|
0.72 (0.51–1.01)
|
|
0.63 (0.30–1.33)
|
|
0.74 (0.50–1.09)
|
"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," write Nakamura and colleagues in the
Lancet. "Thus, in low-risk populations--eg, hypercholesterolemic 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."
According to
Dr Daniel Rader (University of Pennsylvania School of Medicine, Philadelphia), who commented on the study during the late-breaking clinical-trials session at AHA meeting, the MEGA trial is a landmark primary-prevention trial for the Asian population, not unlike the
West of Scotland Coronary Prevention Study (WOSCOPS) and the
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). He said the results support the concept that a modest shift in population cholesterol distribution can have a major impact on the incidence of coronary disease.
Nakamura H, Arakawa K, Itakura H et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA study): a prospective randomised controlled trial. Lancet 2006; 368:1155-63.
Sirtori CR, Calabresi L. Japan: are statins still good for everybody? Lancet 2006; 368:1135-36.
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Heartwire from Medscape © 2006 Medscape
Cite this: Michael O'Riordan. Low-dose statin therapy reduces risk of CHD in Japanese subjects by 33% - Medscape - Sep 28, 2006.
