Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials

摘要: Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their goals. This systematic review meta-analysis investigated the effects of established novel treatment strategies, specifically targeting HDL, on inhibition atherosclerosis cholesteryl ester transfer protein-expressing animals, prevention events randomised controlled trials. Linear regression analyses using data from preclinical studies revealed associations TC non-HDL-C lesion area (R2=0.258, P=0.045; R2=0.760, P<0.001), but not (R2=0.030, P=0.556). In trials, non-fatal myocardial infarction was significantly less group with pooled odd ratios 0.87 [0.81; 0.94] all 0.85 [0.78; 0.93] after excluding some due off-target adverse events, whereas all-cause mortality affected (OR 1.05 [0.99-1.10]). Meta-regression trend towards between-group differences absolute change baseline LDL-C (P=0.066), no correlation found (P=0.955). We conclude that protective role lowering well-established. The contribution disease remains undefined may be dependent mode action HDL-C-modification. Nonetheless, strategies improving HDL function apolipoprotein A-I worth exploring. © 2015 Elsevier B.V. All rights reserved.