Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial

Nakamura, Haruo; Arakawa, Kikuo; Itakura, Hiroshige; Kitabatake, Akira; Goto, Yoshio; Toyota, Takayoshi; Nakaya, Noriaki; Nishimoto, Shoji; Muranaka, Masaharu; Yamamoto, Akira; Mizuno, Kyoichi; Ohashi, Yasuo

doi:10.1016/s0140-6736(06)69472-5

Cited by 941Lipoproteins and Cardiovascular HealthCancer, Lipids, and MetabolismBlood Pressure and Hypertension Studies

Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial

Nakamura, Haruo, Arakawa, Kikuo, Itakura, Hiroshige, Kitabatake, Akira, Goto, Yoshio, Toyota, Takayoshi, Nakaya, Noriaki, Nishimoto, Shoji +4 more·2006·The Lancet

DOI 10.1016/s0140-6736(06)69472-5

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Abstract

Background Evidence-based treatment for hypercholesterolaemia in Japan has been hindered by the lack of direct evidence in this population. Our aim was to assess whether evidence for treatment with statins derived from western populations can be extrapolated to the Japanese population.Methods In this prospective, randomised, open-labelled, blinded study, patients with hypercholesterolaemia (total cholesterol 5.69-6.98 mmol/L) and no history of coronary heart disease or stroke were randomly assigned diet or diet plus 10-20 mg pravastatin daily. The primary endpoint was the first occurrence of coronary heart disease. Statistical analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00211705.Findings 3966 patients were randomly assigned to the diet group and 3866 to the diet plus pravastatin group. Mean follow-up was 5.3 years. At the end of study, 471 and 522 patients had withdrawn, died, or been lost to follow-up in the diet and diet plus pravastatin groups, respectively. Mean total cholesterol was reduced by 2.1% (from 6.27 mmol/L to 6.13 mmol/L) and 11.5% (from 6.27 mmol/L to 5.55 mmol/L) and mean LDL cholesterol by 3.2% (from 4.05 mmol/L to 3.90 mmol/L) and 18.0% (from 4.05 mmol/L to 3.31 mmol/L) in the diet and the diet plus pravastatin groups, respectively. Coronary heart disease was significantly lower in the diet plus pravastatin group than in the diet alone group (66 events vs 101 events; HR 0.67, 95% CI 0.49-0.91; p=0.01). There was no difference in the incidence of malignant neoplasms or other serious adverse events between the two groups.Interpretation Treatment with a low dose of pravastatin reduces the risk of coronary heart disease in Japan by much the same amount as higher doses have shown in Europe and the USA.

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Large-scale Japanese clinical studies showed that treating hyper-LDL cholesterolemia decreased CAD occurrence.
“Large-scale clinical studies conducted in Japan have also reported similar results41–44), in which it was evident that the occurrence of CAD in the Japanese subjects decreased as a result of treating the hyper-LDL cholesterolemia.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [41]
In the MEGA study, the incidence rate of cardiovascular events for the diet therapy group was 2.1 per 1,000 person-years.
“The MEGA study, a primary prevention trial involving the use of statin41), showed that the incidence rate of cardiovascular events for the group that underwent diet therapy was 2.1/1,000 person-years.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [41]
The MEGA study confirmed the effectiveness of LDL-C-lowering therapy using statins to prevent cardiovascular events in Japanese patients with hypercholesterolemia.
“The MEGA study41), a large-scale clinical trial conducted in Japan, confirmed the effectiveness of LDL-C-lowering therapy using statins to prevent cardiovascular events in Japanese patients with hypercholesterolemia.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [41]

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Authors: Nakamura, H., Arakawa, K., Itakura, H., Kitabatake, A., Goto, Y., Toyota, T., Nakaya, N., Nishimoto, S., Muranaka, M., Yamamoto, A., Mizuno, K., & Ohashi, Y.
Affiliations: Mitsukoshi Health and Welfare Foundation (JP)
Fukuoka University (JP)
Ibaraki Christian University (JP)
Hokkaido University (JP)
Tohoku Rosai Hospital (JP)
Yugawara Hospital (JP)
National Cerebral and Cardiovascular Center (JP)
Chiba Hokusou Hospital (JP)
The University of Tokyo (JP)
Corresponding author: Nakamura, Haruo
ORCID: Nishimoto, Shoji
Yamamoto, Akira
Mizuno, Kyoichi
Ohashi, Yasuo
Venue: The Lancet
Publisher: Elsevier BV
Published: 2006-09
Volume: 368
Issue: 9542
Pages: 1155-1163
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(06)69472-5
OpenAlex: W2126678006
Cited by: 941
References: 28
Citations by year: 2026: 14 · 2025: 15 · 2024: 32 · 2023: 39 · 2022: 31 · 2021: 35 · 2020: 44 · 2019: 48 · 2018: 48 · 2017: 39 · 2016: 60 · 2015: 53 · 2014: 78 · 2013: 59 · 2012: 53
FWCI: 52.55
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords: pravastatin, hypercholesterolemia, coronary artery disease, primary prevention, statins, dietary intervention, LDL cholesterol, total cholesterol, Japanese population, adverse events
MeSH terms: Adult, Aged, Anticholesteremic Agents, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Japan, Male, Middle Aged, Pravastatin, Diet, Fat-Restricted

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Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial

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