Purpose: Cholesterol lowering with statins and fibrates is a cornerstone of preventive cardiology. There is, however, little data on the magnitude of reduction in different endpoints in various high risk populations. In this analysis, we sought to determine how cholesterol lowering lowers the risk of cardiovascular death (CV death), myocardial infarction (MI) and stroke (CVA) in different populations.
Method: We performed a literature search to identify all clinical trials from 1994 onward for cholesterol lowering with statins or fibrates. Thirty two studies were identified and then segregated into 5 separate categories based on the underlying cardiovascular risk: Primary prevention (N=6), secondary prevention (N=8), comparison of drug dose in secondary prevention (N=8), significant comorbid conditions (N=6), and fibrates (N=4). Separate meta-analyses were performed for the three different endpoints for each of these 5 categories.
Result: Primary and secondary prevention populations had significant reduction in all categories: CV death (25 and 22% reduction respectively), MI (41% and 32% reduction), and CVA (23% and 21% reduction). High dose versus low dose statins did not significantly decrease CV death, but had continued further significant reduction in MI (22%) and CVA (13%). Treatment with statins in comorbid diseases, such as heart failure and renal failure did not affect CV death or CVA, but did lower risk of MI by 23%. Fibrate therapy, based on these 4 studies, did not significantly affect CV death or CVA, but had a borderline significant decrease in MI of 18%. Rates for CV death ranged from 0.3% per year for primary prevention to 5.15% with cormorbidities. MI rates were similar at approximately 1.1% per year in all groups except primary prevention (0.56%). CVA rates were lowest in primary prevention (0.46% and highest in patients with comorbidities (1.2%).
Conclusion: This data suggests that while there is a virtually uniform relative risk reduction of MI with cholesterol lowering with statins or fibrates, this effect is not necessarily carried over to reduction in CVA or CV death. The underlying comorbidities, disease processes, and the extent of relative and absolute risk reduction in each of these three endpoints need to be assessed separately in defining the expected benefit of cholesterol reduction in diverse populations.