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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.
- Source :
-
European Journal of Pharmacology . Sep2015 Part A, Vol. 763, p48-63. 16p. - Publication Year :
- 2015
-
Abstract
- 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 HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This systematic review and meta-analysis investigated the effects of established and novel treatment strategies, specifically targeting HDL, on inhibition of atherosclerosis in cholesteryl ester transfer protein-expressing animals, and the prevention of clinical events in randomised controlled trials. Linear regression analyses using data from preclinical studies revealed associations for TC and non-HDL-C and lesion area ( R 2 =0.258, P =0.045; R 2 =0.760, P <0.001), but not for HDL-C ( R 2 =0.030, P =0.556). In clinical trials, non-fatal myocardial infarction risk was significantly less in the treatment group with pooled odd ratios of 0.87 [0.81; 0.94] for all trials and 0.85 [0.78; 0.93] after excluding some trials due to off-target adverse events, whereas all-cause mortality was not affected (OR 1.05 [0.99–1.10]). Meta-regression analyses revealed a trend towards an association between between-group differences in absolute change from baseline in LDL-C and non-fatal myocardial infarction ( P =0.066), whereas no correlation was found for HDL-C ( P =0.955). We conclude that the protective role of lowering LDL-C and non-HDL-C is well-established. The contribution of raising HDL-C on inhibition of atherosclerosis and the prevention of cardiovascular disease remains undefined and may be dependent on the mode of action of HDL-C-modification. Nonetheless, treatment strategies aimed at improving HDL function and raising apolipoprotein A-I may be worth exploring. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 763
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 109445467
- Full Text :
- https://doi.org/10.1016/j.ejphar.2015.03.089