W.H.O. cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up. Report of the Committee of Principal Investigators.

This is a further report on the mortality amongst men in the W.H.O. cooperative trial of the primary prevention of ischaemic heart disease (IHD) by clofibrate. Mean observation was 9.6 years, 5.3 in the trial and 4.3 afterwards; 911 deaths are recorded in 150 000 man-years. There were 25% more deaths in the clofibrate-treated group than in the comparable, high serum cholesterol, control group (p < 0.01), and there was an excess in the treated group in all the three participating centres. Mortality from all causes was higher in the treated group than in the high cholesterol controls during the trial, equal in the first two years after leaving the trial, but higher again after that. No particular disease accounted for the overall excess: the treated group had more deaths from IHD, stroke, cancer, and other major diseases though most of these differences were not individually significant. There was no excess in deaths due to accidents and violence. There was also a significant excess in the death rate from all causes, and from causes other than IHD, in the treated group compared with the second, low cholesterol, control group. No relationship could be shown between the excess mortality and cholesterol reduction, or the length of time on clofibrate. Explanation of the excess mortality is not apparent: a long term toxic effect of clofibrate, the possible consequences of reducing body cholesterol pools and, remotely, chance have all to be considered.

RCT Entities:   Population Interventions Outcomes