LUNG-CANCER MORTALITY AFTER 16 YEARS IN MRFIT PARTICIPANTS IN INTERVENTION AND USUAL CARE GROUPS

PURPOSE: The Multiple Risk Factor Intervention Trial (MRFIT), a random ized clinical trial for the primary prevention of coronary heart disea se, enrolled 12,866 men (including 8194 cigarette smokers) aged 35-57 years at 22 clinical centers across the United States. Participants we re randomized either to special intervention (SI), which included an i ntensive smoking cessation program, or to usual care (UC). After 16 ye ars of follow-up, lung cancer mortality rates were higher in the SI th an in the UC group. Since rates of smoking cessation in SI were higher than those for UC for the 6 years of the trial, and since risk of lun g cancer mortality is known to decline with smoking cessation, these r esults were unexpected. The purpose of the present study was to invest igate hypotheses that could explain the higher observed lung cancer mo rtality rates in the SI as compared with the UC group. METHODS: Analyt ic methods were employed to determine whether SI and UC participants d iffered either in baseline characteristics or in characteristics that changed during the trial and to determine whether these differences co uld explain the higher rates of lung cancer mortality among SI as comp ared to UC participants. Rates of mortality from coronary heart (CHD) were examined to explore the possibility that prevention of CHD death may have contributed to greater mortality due to lung cancer in the SI group. RESULTS: From randomization through December 1990, 135 SI and II? UC participants died from lung cancer. The relative difference bet ween the SI and U groups adjusted for age and number of cigarettes smo ked per day, was 1.17 (95% CI:0.92-1.51). The greatest difference betw een the SI and UC groups in lung cancer mortality rates occurred among the heaviest smokers at baseline who did not achieve sustained smokin g cessation by year 2. In this group the rates of death from CHD were approximately the same among the SI and UC subjects. No differences in baseline characteristics were found between SI and UC smokers who did not achieve sustained cessation by year 2, and there were no differen ces;in follow-up characteristics between the two study groups that cou ld explain the difference in lung cancer mortality. CONCLUSIONS: None of the hypotheses proposed to explain the unexpected higher rates of l ung cancer mortality among SI as compared with UC subjects were sustai ned by the data. Thus we conclude that the difference observed is due to chance, and that a longer period of sustained smoking cessation plu s follow-up is necessary to detect a reduction in lung cancer mortalit y as a result of smoking cessation intervention in a randomized clinic al trial. (C) 1997 by Elsevier Science Inc.