Multiple Risk Factor Intervention Trial - MRFIT


Risk factor modification for mortality in CAD.


Modification of elevated serum cholesterol levels, hypertension, and cigarette smoking in persons at increased risk of death from heart attacks would result in reduction of coronary death rates.

Study Design

Study Design:

Patients Screened: 361,662
Patients Enrolled: 12,866
Mean Follow Up: 7 years
Mean Patient Age: 46
Female: 0

Patient Populations:

Upper 15% of a risk score distribution based on data from the Framingham Heart Study.


Low risk
History of heart attack
Diabetes Mellitus requiring medication
Expected geographic mobility
Serum cholesterol level of 350 mg/dL or higher
Diastolic blood pressure of 115 mmHg or higher (at first screening) and 120 mmHg or higher (at second screening)
Body weight >150% of desirable weight
Angina pectoris as determined by Rose Questionnaire
History or ECG evidence of myocardial infarction (MI)
Untreated symptomatic diabetes
Diets incompatible with the MRFIT food pattern
Treatment with guanethidine, hydralazine, insulin, oral hypoglycemic agents, or lipid-lowering agents
Illnesses or disabilities likely to impair full participation in the trial

Primary Endpoints:

Death from CHD

Secondary Endpoints:

Death from cardiovascular disease, death from any cause, the combination of fatal CHD and nonfatal MI.

Drug/Procedures Used:

Special intervention treatment for hypertension with hydrochlorothiazide or chlorthalidone as the first drug. Reserpine, hydralazine, guanethidine, or certain native drugs were added sequentially if the goal blood pressure was not achieved. Counseling on cigarette smoking and dietary advice about lowering blood cholesterol levels were given.

Principal Findings:

At 7 years of follow-up, mortality from coronary heart disease was 17.9 deaths/1000 in the special intervention group and 19.3 deaths/1000 in the group receiving usual care.

Surprisingly, at 7 years of follow-up, total mortality rates were 41.2 deaths/1000 in the in the special intervention group and 40.4 deaths/1000 in the group receiving usual care.

At 10.5 years of follow-up, for those with baseline diastolic blood pressure of 90 to 99 mmHg and for those with baseline resting electrocardiographic abnormalities, favorable posttrial mortality findings for the special intervention group were a reversal of unfavorable trends recorded during the 7-year trial. Two factors appear to have contributed to this more favorable mortality trend for the special intervention group:
A change in the diuretic treatment protocol for men in the special intervention group about 5 years after randomization, which involved replacement of hydrochlorothiazide with chlorthalidone at a daily maximum dose of 50mg; and a favorable effect of intervention on nonfatal cardiovascular events during the trial years. In addition, delay until the full impact of beneficial effects on mortality end points from smoking cessation and cholesterol lowering could have contributed.

Black race, cigarette smoking, diabetes, and hypertension are independently associated with idiopathic dilated cardiomyopathy in men.


After 7 years of follow-up, men with hypertension, primarily those with resting ECG abnormalities, had no favorable, and possibly an unfavorable response to intervention.

At 10.5 years of follow-up, the mortality trend for hypertensive men in the special intervention group was reversed, possibly because of the following reasons:
Late effects on mortality rates of the lower rate of nonfatal cardiovascular events in the special intervention group than in the group receiving usual care.
Time delay for impact of risk factor intervention on mortality rates of the special intervention group effects of the changes in the protocol for diuretic use for hypertensive men in the special intervention group.

The 10.5-year mortality data support the inference that a multifactor intervention program such as that used in MRFIT has long-term beneficial effects for persons with hypertension.


1. JAMA 1982;248:1465-77. Final results
2. Circulation 1990;82:1616-28. 10.5 year survival follow-up
3. Am J Epidemiol 1994;139:166-72. Predictors of mortality
4. JAMA 1997;277:1293-8. ESRD 16-year follow-up
5. Lancet 1998;351:934-9. Socioeconomics and mortality

Keywords: Follow-Up Studies, Chlorthalidone, Reserpine, Diuretics, Guanethidine, Counseling, Coronary Disease, Risk Factors, Electrocardiography, Vasodilator Agents, Cholesterol, Hydralazine, Sympatholytics, Clinical Protocols, Hydrochlorothiazide, Hypertension, Smoking Cessation, Cardiomyopathy, Dilated, Diabetes Mellitus

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