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Multiple risk factor intervention trial revisited: a new perspective based on nonfatal and fatal composite endpoints,
Jeremiah Stamler1, James D Neaton, Jerome D Cohen
1Northwestern University Medical School, Chicago, IL, USA.
Insights
The Multiple Risk Factor Intervention Trial found that a special intervention significantly reduced composite cardiovascular disease (CVD) and coronary heart disease (CHD) events in men over 7 years. These results support lifestyle changes for CVD prevention.
Area of Science:
- Cardiology
- Preventive Medicine
- Public Health
Background:
- The Multiple Risk Factor Intervention Trial (MRFIT) investigated a multifactor intervention for coronary heart disease (CHD) in 12,866 men.
- Initial 7-year follow-up showed no significant difference in primary endpoints between the special intervention (SI) and usual care (UC) groups, partly due to lower-than-expected event rates.
Purpose of the Study:
- To determine post-trial cardiovascular disease (CVD) mortality risks associated with nonfatal CVD events during the MRFIT trial.
- To create new composite outcomes by combining during-trial deaths with nonfatal events that predicted future CVD mortality.
- To re-evaluate the effectiveness of the SI versus UC in preventing fatal and nonfatal cardiovascular outcomes.
Main Methods:
- Cox regression analysis was used to assess the association between nonfatal CVD events during the trial and subsequent CVD mortality over 20 years.
- Nonfatal events with a >2-fold increased risk of CVD death were identified.
- Two composite outcomes were constructed: a CHD composite and a CVD composite, including during-trial deaths and identified high-risk nonfatal events.
Main Results:
- Six of ten during-trial nonfatal events were significantly (P<0.001) associated with a >2-fold increased risk of CVD death.
- The CHD composite outcome occurred in 520 SI men and 602 UC men (hazard ratio [HR]=0.86; 95% CI, 0.76-0.97; P=0.01).
- The CVD composite outcome occurred in 581 SI men and 652 UC men (HR=0.89; 95% CI, 0.79-0.99; P=0.04).
Conclusions:
- Post hoc analyses revealed significantly lower composite fatal/nonfatal CHD and CVD rates over 7 years in the SI group compared to the UC group.
- These findings support the reinforcement of recommendations for improved dietary and lifestyle practices.
- The study suggests that these interventions, supplemented with pharmacological therapy as needed, are effective in preventing and controlling major CVD risk factors.
Background:
The Multiple Risk Factor Intervention Trial evaluated a multifactor intervention on coronary heart disease (CHD) in 12 866 men. A priori defined endpoints (CHD death, CHD death or nonfatal myocardial infarction, cardiovascular disease [CVD] death, and all-cause death) did not differ significantly between the special intervention (SI) and usual care (UC) groups over an average follow-up period of 7 years. Event rates were lower than anticipated, reducing power. Other nonfatal CVD outcomes were prespecified but not considered in composite outcomes comparing SI with UC.
Methods And Results:
Post-trial CVD mortality risks associated with nonfatal CVD events occurring during the trial were determined with Cox regression. Nonfatal outcomes associated with >2-fold risk of CVD death over the subsequent 20 years were combined with during-trial deaths to create 2 new composite outcomes. SI/UC hazard ratios and 95% confidence intervals were estimated for each composite outcome. Of 10 during-trial nonfatal events, 6 were associated (P<0.001) with >2-fold risk of CVD death. A CHD composite outcome (CHD death, myocardial infarction [clinical or serial ECG change], CHF, or coronary artery surgery) was experienced by 520 SI and 602 UC men (SI/UC hazard ratio = 0.86; 95% confidence interval, 0.76-0.97; P=0.01). A CVD composite outcome (CHD [as above], other CVD deaths, stroke, or renal impairment) was experienced by 581 SI and 652 UC men (hazard ratio = 0.89; 95% confidence interval, 0.79-0.99; P=0.04).
Conclusions:
In post hoc analyses, composite fatal/nonfatal CHD and CVD rates over 7 years were significantly lower for SI than for UC. These findings reinforce recommendations for improved dietary/lifestyle practices, with pharmacological therapy as needed, to prevent and control major CVD risk factors.
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