Simultaneous low-density lipoprotein-C lowering and high-density lipoprotein-C elevation for optimum cardiovascular disease prevention with various drug classes, and their combinations: a meta-analysis of 23 randomized lipid trials

Purpose of review Our analysis presents an alternative hypothesis to the prevailing view that low-density lipoprotein-C is the only important target of lipid therapy. Recent findings Two recently published studies showed surprising results. In the Armed Forces Regression Study, low-density lipoprotein-C was lowered only 22% with cholystyramine, niacin and gemfibrozil. Coronary stenosis regressed, however, and the primary clinical event rate was reduced by 54%. Conversely, in the FIELD trial, the primary event rate reduction was only 11% (P = NS). These differences appeared to be explained largely by the difference in high-density lipoprotein response to these regimens (38 vs. 3%). This meta-analysis of 23 trials strongly supports the notion that the sum of percent reduction in low-density lipoprotein-C plus percent increase in high-density lipoprotein-C predicts benefits much more effectively than either lipoprotein component. Summary Epidemiology suggests that the cardiovascular event rate is reduced by nearly 1% for each 1% reduction in low-density lipoprotein-C and by at least 1% for each 1% increase in high-density lipoprotein. These effects are statistically independent; thus, for moderate lipid changes, they are additive. If this simple algorithm is proven accurate, a 30% high-density lipoprotein-C increase and a 40% low-density lipoprotein-C reduction would result in a nearly 70% CHD risk reduction - and a revolution in cardiovascular prevention.