Compliance with medication in the helsinki heart study

Summary

Compliance with medication has a decisive influence on the findings in clinical intervention studies, so the reliable estimation of compliance is vital to the success of such research. This report describes the main findings about compliance in the Helsinki Heart Study, a five-year, double-blind, primary prevention trial of gemfibrozil as a lipid-lowering agent compared with placebo, in 4,081 dyslipidaemic middle-aged men. Three estimation methods were employed: capsule counting at every three-month follow-up visit, urine gemfibrozil analysis at six-month intervals, and, a novel technique, a digoxin marker added to both gemfibrozil and placebo capsules at the end of the third and fifth study years. The estimates of compliance for the study population as a whole generated by these three methods are discussed here.

The mean daily capsule count showed that 36% of patients on gemfibrozil men and 39% of those on placebo took more than 90% of their capsules, while only 5% of both groups consumed half or less of the prescribed treatment. According to urinary gemfibrozil analysis, 30% of gemfibrozil subjects had more than 90% positive results and 28% had half or fewer positive. Among study completers, there were 42% gemfibrozil subjects and 50% placebo subjects who on both occasions had the good result in the digoxin marker analysis, while 14% of the gemfibrozil men and 12% of the placebo men scored ‘poor’ in both marker analyses. Capsule counting revealed a slight deterioration in compliance over the trial period, which was confirmed by the other two methods; for example, the proportion of positive results in the semiannual urine gemfibrozil analyses decreased from 76% to 65%. Medication compliance was slightly better in the placebo group according to capsule counting and digoxin marker methods.

In the Helsinki Heart Study there were 34% fewer cardiac end points among participants in the gemfibrozil group compared to placebo. The reduction occurred in a study group with 30% drop outs and with about 20% of study completers having poor medication compliance, according to all three methods.