Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 47

Multiple Risk Factor Intervention Trial

Lynn E. Eberly, Jeremiah Stamler, Lewis H. Kuller, and James D. Neaton

47.1 Introduction

The Multiple Risk Factor Intervention Trial (MRFIT) was a nationwide randomized trial on primary prevention of coronary heart disease (CHD) death, sponsored by the National Heart, Lung, and Blood Institute within the United States National Institutes of Health, and it was conducted during 1972–1982. The study cohort consisted of men (baseline ages 35–57 years) at higher risk for CHD death, but with no clinical evidence of cardiovascular disease (CVD); women were not included because of substantially lower CHD rates. The intervention tested was multifactor: intensive counseling for smoking cessation, dietary advice particularly to lower serum cholesterol, and stepped-care pharmacologic treatment for hypertension (primarily with diuretics). The primary outcome was CHD mortality, with an observation period of 6 years minimum and 7 years on average [1,2]. Since the end of active follow-up in 1982, the 361,662 men who were screened during MRFIT recruitment, which includes the 12,866 who were randomized, have been followed for mortality date and cause through Social Security Administration and National Death Index searches [3,4].

47.2 Trial Design

47.2.1 Overview

The objective of MRFIT was to test whether a multifactor intervention would result in lower CHD mortality among men, baseline ages 35–57 years, at higher risk for CHD as measured by three ...