Obstacles and options in the quest for drug candidates against vascular disease.

The difficulties in cardiovascular drug development have been exposed by recent clinical trials, which have uncovered various limitations of promising drug candidates. Yet, the imperative to improve medical treatment of atherosclerosis in aging populations afflicted by metabolic disease remains unbroken. Herein alternatives to metabolically active compounds such as glitazones and torcetrapib are introduced and discussed, namely CC chemokine receptor 5 (CCR5) antagonists recently approved for treatment of patients with human immunodeficiency virus-1, interceptors of proatherogenic chemokine interactions, and actively protective pathways. A combination of different strategies may yield improved safety profiles of these therapeutics.