CARDIAC AND NONCARDIAC MORTALITY IN RANDOMIZED CLINICAL TRIALS OF CHOLESTEROL LOWERING AGENTS

Randomized clinical trials (RCT) of cholesterol lowering studies have contributed to significant changes in management of coronary artery disease in the past 15 years.  There is, however, no data on how well the patients studied are representative of the overall population.  To this end, we developed a standardized method for assessing mortality in published clinical trials controlling for the variations in age and proportion of each gender reported in the clinical trials.  We then evaluated the control group studied in published RCT’s evaluating various drugs to lower cholesterol.  Of the 11 studies evaluated, 3 studies were for primary prevention and 8 were for secondary prevention.  The average age in these studies ranged from 55-73 years.  The percentage of men ranged from 63-100% in these trials.  All of the studies evaluated only “high risk” patients. Noncardiac mortality in the 3 primary prevention trials averaged 52% of what would be expected in an unselected similarly age and gender matched population (30% for AFCAPS/TexCAPS, 44% for ASCOT, 83% for CARDS).  In the 8 secondary prevention trials, noncardiac mortality averaged 67% of the expected mortality (range 33%-107%). Cardiac mortality in the 3 primary prevention trials averaged 80% (AFCAPS 40%, ASCOT 84%, CARDS 115%) of expected mortality, while cardiac mortality was 250% of expected (range 105%-795%) in the secondary prevention RCTs.  The TNT and ILLUMINATE studies, which utilized active controls, had cardiac mortality similar to that of an unselected similarly age and gender matched population and noncardiac mortality that was 45% of expected.

Conclusion:  Noncardiac mortality in both primary and secondary studies of cholesterol lowering is significantly lower than would be expected compared to unselected similarly age and gender matched populations.  Cardiac mortality in primary prevention studies is also extremely low, while there is a wide range in secondary prevention trials.  Care must be utilized in extrapolating the mortality seen in these studies to the population as a whole.