Saturday, November 19, 2005

Japanese study: small LDL reductions = big CHD

De: Marcelo Gustavo Colominas [mailto:mgcolominas@hotmail.com]
Enviada em: sexta-feira, 18 de novembro de 2005 22:09
Para: undisclosed-recipients:
Assunto: MEGA (AHA News)


MEGA: Japanese study finds small LDL reductions translate into big CHD
protection

Nov 16, 2005. Michael O'Riordan
Dallas, TX - The addition of a low-dose statin to a low-fat diet rich in
fish reduced the risk of coronary heart disease in a Japanese study of
individuals with moderately elevated cholesterol levels. Investigators
report that the combination of diet and pravastatin 10 mg reduced the risk
of CHD by 33%, approximately the same reduction observed in US and European
primary-prevention trials that have used larger statin doses.


The results of the Management of Elevated Cholesterol in the Primary
Prevention Group of Adult Japanese (MEGA) study were presented today at the
American Heart Association Scientific Sessions 2005. Lead investigator Dr
Haruo Nakamura (National Defense Medical College, Saitama, Japan) said the
purpose of the Japanese study was to examine whether the addition of a
low-dose statin to a diet rich in omega-3 fatty acids could reduce the risk
of CHD. In Japan, the incidence of coronary disease is about one third lower
than the US and Europe, where most of the statin trials have been conducted,
but the risk of stroke and cancer is higher.

Dr Daniel Rader (University of Pennsylvania School of Medicine,
Philadelphia), who commented on the study during the late-breaking
clinical-trials session, called the MEGA study 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 and will spur debate about the
role low-dose statin therapy might have in achieving such a shift.

"The MEGA study will undoubtedly have a major impact on the treatment of
hypercholesterolemia in Asia, as it provides reassurance of safety and proof
of benefit of low-dose statin therapy," said Rader. "It should have impact
in the West, as well. These results suggest that the potential for the
broader use of low-dose statin therapy make it important to utilize
available approaches to identify that subset of healthy individuals who are
at high risk and may merit statin therapy despite only modestly elevated LDL
cholesterol."

Relatively low risk patients

The MEGA study was a prospective, randomized, open-label trial comparing
diet and pravastatin 10 mg with diet alone for the reduction of
first-occurrence CHD in 7832 patients. Of those randomized to statin
therapy, approximately 25% were uptitrated to the 20-mg dose of pravastatin.
The diet followed by patients was low in total cholesterol, low in saturated
fat, and included at least three servings of fish per week.

Average baseline LDL cholesterol levels were 156 mg/dL in both study arms
before treatment. Mean HDL-cholesterol levels were relatively high,
measuring 57 mg/dL in both treatment groups. 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. Although
the absolute benefit was small, a little over a 1% absolute reduction in
risk, the number needed to treat to prevent one additional CHD event was
119.

MEGA: Primary and secondary end points

End point
Hazard ratio (95% CI)

Coronary heart disease (a composite end point of fatal/nonfatal MI, angina,
cardiovascular death, need for revascularization)
0.67 (0.49-0.91)

Coronary heart disease and cerebral infarction
0.70 (0.54-0.90)

Stroke
0.83 (0.57-1.21)

Total mortality
0.72 (0.51-1.01)

Speaking with heartwire, Nakamura said that the relatively small reduction
in LDL-cholesterol levels translated into a statistically significant
reduction in CHD risk, a reduction similar to those observed in the major
lipid-lowering studies. Asked why the 10- to 20-mg dose of pravastatin
yielded benefit that was previously achieved with 20- to 40-mg doses of
pravastatin in the US and Europe, he said he suspects that the traditional
Japanese diet and baseline HDL-cholesterol levels were cardioprotective.

"We understand that LDL cholesterol is very important for developing
coronary heart disease, but not only LDL is important. Levels of HDL are
also important, and there are many studies that have showed a protective
benefit of HDL cholesterol against coronary heart disease. In general,
Japanese people usually have high HDL cholesterol, about 10 mg/dL higher
than people in the US, so this might have provided some protective benefit
that allowed us to reduce the dose of statin in this trial."

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