THE HELSINKI-HEART-STUDY - AN 8.5-YEAR SAFETY AND MORTALITY FOLLOW-UP

Earlier monitoring of all symptoms, hospital admissions, cancer diagno ses and causes of death during gemfibrozil treatment had raised some s uspicions which called for further follow-up. Design. Close monitoring of selected, potentially adverse events amongst treated subjects afte r a placebo-controlled trial and comparing occurrences to those in var ious untreated groups. Setting. All participants of the Helsinki Heart Study (a controlled, 5-year, multi-clinic coronary heart disease (CHD ) primary prevention trial with gemfibrozil and placebo) were offered gemfibrozil treatment and twice yearly follow-up for 3.5 years. Untrea ted groups in the source population and national cancer statistics wer e utilized in comparisons. Subjects. Of the 2046 dyslipidaemic men ini tially randomized to gemfibrozil, 2002 survivors entered the 3.5-year follow-up; of the 2035 initial placebo men, 1992 continued to be monit ored. Interventions. Gemfibrozil was chosen for the followup by 66.3% of the gemfibrozif-treated and 68.5% of the placebo-treated men. Main outcome measures. Gastrointestinal symptoms, surgery, strokes, cancer incidence, mortality by cause. Results, Gastrointestinal symptoms rema ined more common in the original gemfibrozil group. After 8.5 years st rokes numbered 32 (gemfibrozil) vs. 37 (placebo), violent deaths 16 vs . 14, and cancers 51 in both groups. Total mortality was equal during the original 5 years, but higher in the gemfibrozil group post-trial, leading to an 8.5 year mortality of 101 vs. placebo 83 (P = 0.19). Thi s was mainly a result of higher cancer mortality in the gemfibrozil (3 0) than the placebo group (18, P = 0.08). An additional 18-month post- study registry follow-up disclosed 13 placebo and five gemfibrozil can cer deaths, altering the cancer mortality to gemfibrozil 35 vs. placeb o 31 at 10 years. Conclusions. The most plausible explanation for the discrepancy between cancer incidence and cancer-specific mortality, ba sed mainly on comparison with untreated groups, is delayed diagnosis. The increased cancer and total mortality is most probably due to chanc e, based on the later reversal of trends.