Abstract 6280: Meta-Analysis of the Relationship between Non-High Density Lipoprotein Cholesterol Reduction and Coronary Heart Disease Risk
To determine the relationship between non-high density lipoprotein cholesterol (non-HDL-C) lowering and coronary heart disease (CHD) risk reduction for various lipid-modifying therapies. Non-HDL-C is the guideline-defined secondary target of therapy after LDL-C. Whether the method of lowering non-HDL-C influences CHD risk is unknown. Randomized, placebo or active-controlled trials were evaluated. The effect of mean non-HDL-C reduction on the relative risk of nonfatal myocardial infarction and CHD death was estimated using Bayesian random-effects meta-analysis models adjusted for study duration. Cochrane’s Q was used to test for heterogeneity. Study inclusion criteria were met by 14 statin (n=100,827), 7 fibrate (n=21,647), and 6 niacin (n=4445) trials, and 1 trial each of a bile acid sequestrant (n=3806), diet (n=458), and partial ileal bypass surgery (n=838). For statins, each 1% decrease in non-HDL-C resulted in a 0.99% (95% CI 0.98% – 1.00%) decrease in CHD risk over 4.5 years. Although the fibrate model did not differ from the statin model (Bayes factor K=0.49), there was a suggestion that the relationship between non-HDL-C and CHD risk differed by fibrate type. For each 1% reduction in non-HDL-C, in the 2 fenofibrate trials demonstrated a 0.7% reduction in CHD risk versus 2–3% reductions in risk for the 2 gemfibrozil trials; however, homogeneity could not be excluded (Q 3.66, 6 df; p=0.68). The niacin model was moderately different from the statin model (K=7.43), with heterogeneity among the trials (Q 11.8, df 5; p=0.038). The only niacin monotherapy trial (n=3908) had a 1:1 relationship between non-HDL-C and risk reduction. No consistent relationships were apparent for the 5 small trials of niacin in combination. The 95% CIs for the diet, bile acid sequestrants, and surgery trials also included the 1:1 relationship. These findings support the use of non-HDL-C as an important target of therapy for CHD prevention. Most lipid-modifying drugs used as monotherapy have an approximately 1:1 relationship between percent non-HDL-C lowering and CHD reduction, although this relationship may vary by type of fibrate. Small trial sizes limit conclusions regarding niacin used in combination.