Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project.
The Coronary Drug Project was carried out to evaluate the efficacy and safety of several lipid-influencing drugs in the long-term treatment of coronary heart disease. The five-year mortality in 1103 men treated with clofibrate was 20.0 per cent, as compared with 20.9 per cent in 2789 men given placebo (P = 0.55). Good adherers to clofibrate, i.e., patients who took 80 per cent of more of the protocol prescription during the five-year follow-up period, had a substantially lower five-year mortality than did poor adherers to clofibrate (15.0 vs. 24.6 per cent; P = 0.00011). However, similar findings were noted in the placebo group, i.e., 15.1 per cent mortality for good adherers and 28.3 per cent for poor adherers (P = 4.7x10-16). These findings and various other analyses of mortality in the clofibrate and placebo groups of the project show the serious difficulty, if not impossibility, of evaluating treatment efficacy in subgroups determined by patient responses (e.g., adherence or cholesterol change) to the treatment protocol after randomization.