METAANALYSIS OF RESULTS FROM CLINICAL-TRIALS ON PREVENTION OF CORONARY HEART-DISEASE BY LIPID-LOWERING INTERVENTIONS

The efficacy of lipid-lowering interventions for the prevention of coronary heart disease (CHD) has been assessed in several clinical trials. A summary of the published results from controlled trials involving various primary and secondary preventive interventions has been performed using meta-analysis techniques. Non-randomized trials involving either multifactorial interventions or those no longer used in this indication were not included. Nineteen trials, with a total of 48 273 patients, were included in the analysis. The intervention assessed was a drug in 11 trials, a diet in seven others and surgery in the last. Seven trials involved primary prevention and the other 12 involved secondary prevention. The number of patients included per trial varied between 143 and 10 627 and the mean length of follow-up ranged from 0.9 to 9.7 years. At entry, the mean age varied between 45 and 59 years, and the mean serum cholesterol concentration varied between 6.05 and 7.78 mmol/l. The mean decrease in serum cholesterol concentration was between 0.28 and 2.70 mmol/l. The analysis, performed with the logarithm of the odds ratio (OR) method, with the level of significance set at 0.01, showed a significant decrease in the incidence of non-fatal myocardial infarction (MI) (14 trials; 30 370 patients; common OR = 0.75; p < 10(-3)). There was also a slight, significant reduction in the incidence of death due to CHD (15 trials; 39 175 patients; common OR = 0.88; p = 0.004), and no effect was observed on the incidence of death from all causes (16 studies; 47 005 patients; common OR = 0.99; p = 0.78). Non-significant increases in the incidence of death due to cancer (11 trials; 37 495 patients; common OR = 1.23; p = 0.057) and mortality not caused by illness (10 trials; 28 438 patients; common OR = 1.36; p = 0.10) were also noted. Heterogeneity testing was not significant at p = 0.05, for all criteria. The individual analysis on trials involving primary or secondary preventative treatment gave similar results. It remains unclear as to why the observed reduction in the incidence of CHD does not affect death from all causes. This may be due to either treatment or follow-up being too short, or there may be some unidentified toxic effects, although the meta-analysis did not show any significant differences in death caused by cancer or by accident.