MEGA Trial

Management of Elevated Cholesterol in the Primary

Prevention Group of Adult Japanese (MEGA) Trial

Presented at
The American Heart Association
Scientific Session 2005
Presented by Dr. Haruo Nakamura

MEGA Trial: Background

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
The goal of this 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.

www. Clinical trial results.org

Presented at AHA 2005

MEGA Trial
7,832 men age 40-70 years and postmenopausal women up to age 70
with total cholesterol 220-270 mg/dL
Mean
Mean BMI
BMI 23.8
23.8 kg/m2,
kg/m2, 21%
21% Diabetics,
Diabetics, 20%
20% Current
Current Smokers,
Smokers,
baseline
baseline total
total cholesterol
cholesterol 242.6
242.6 mg/dL,
mg/dL, LDL
LDL 157
157 mg/dL,
mg/dL, HDL
HDL 57.5
57.5 mg/dL,
mg/dL, triglycerides
triglycerides 127
127 mg/dL
mg/dL
32%
32% Female,
Female, Mean
Mean Age
Age 58
58 years,
years, Mean
Mean Follow-Up
Follow-Up 5.3
5.3 years
years
Prospective.
Prospective. Randomized.
Randomized. Open-label.
Open-label.

Diet Modification
n=3,966

Diet Modification + Pravastatin

10-20 mg/day

n=3,866

Primary Endpoints: Composite

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

Secondary Endpoints: Stroke,

Stroke, CHD
CHD composite
composite or cerebral infarction, any
cardiovascular event, total
total mortality.
mortality.
www. Clinical trial results.org

Presented at AHA 2005

MEGA Trial: Cholesterol and Triglyceride Levels

LDL

mg/dL

Total
Cholesterol

www. Clinical trial results.org

HDL

Triglycerides
Total cholesterol
reduction was larger in
the pravastatin group
LDL reduction was
greater in the
pravastatin group
HDL increase was
greater in the
pravastatin group
Triglyceride reduction
was greater in the
pravastatin group

Presented at AHA 2005

MEGA Trial: Primary Composite Endpoint

Primary composite endpoint of coronary
heart disease events

# per 1000 patient years

p = 0.01

www. Clinical trial results.org

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).

Presented at AHA 2005

MEGA Trial: Secondary Endpoints

Total mortality was non-significantly lower in the pravastatin group (2.7 vs 3.8, HR
0.71, p=0.055)
MI occurred less often in the pravastatin group (0.9 vs 1.6, p=0.03)
No significant difference was observed in stroke (2.5 vs 3.0, p=0.33) or cerebral
infarction plus TIA (2.0 vs 2.6, p=0.23)

# per 1000 patient years

p=0.055

www. Clinical trial results.org

p=0.33
p=0.23
p=0.03

Presented at AHA 2005

MEGA Trial: Secondary Endpoints cont.

Composite of CHD event or cerebral infarction

# per 1000 patient years

p = 0.005

www. Clinical trial results.org

The composite of CHD

event or cerebral
infarction was lower in
the pravastatin group
(5.0 vs 7.1, p=0.005)

Presented at AHA 2005

MEGA Trial: Safety Data

Frequency of elevated liver
function abnormalities (%)

# per 1000 patient years

Frequency of cancer
(per 1000 patient years)

There was no difference in the frequency of cancer or elevated

liver function abnormalities and no cases of rhabdomyolysis.
www. Clinical trial results.org

Presented at AHA 2005

MEGA Trial: Summary

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 followup.
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 U.S. 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 a modest reduction in lipid parameters.
www. Clinical trial results.org

Presented at AHA 2005