Pharmaceutical strategies for reducing LDL-C and risk of cardiovascular disease

A key strategy in preventing cardiovascular (CV) disease is the reduction of low-density lipoprotein cholesterol (LDL-C). Statins are a crucial therapy for achieving LDL-C reductions, with the highest tolerated dose often prescribed, especially for patients who are at the greatest risk of CV disease. However, statin intolerance, heterogeneous responses to statins and non-adherence make alternative therapies necessary in some cases. Statins can be combined with a multitude of therapies with synergistic mechanisms of action to effectively manage lipid profiles, while improving safety and tolerability profiles. Addition of a cholesterol absorption inhibitor, bile acid sequestrant or fibrate to statin therapy leads to greater numbers of patients achieving and maintaining LDL-C goals. Furthermore, combination therapies can alter the plasma profiles of other molecules involved in hypercholesterolaemia, including triglycerides and high-density lipoprotein cholesterol. An additional strategy is proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition therapy, for use in patients who are statin intolerant, patients with heterozygous or homozygous familial hypercholesterolaemia, and patients at very high CV risk, as a potential means for achieving large LDL-C reductions and maintaining LDL-C goals. Clinical trials have demonstrated that PCSK9 inhibition therapy is not only effective but can also be combined with statin therapy to ensure greater reductions in LDL-C. Current, ongoing studies are investigating the efficacy of novel therapies, including selective peroxisome proliferator-activated receptor (PPAR) alpha modulators, PCSK9-specific ribonucleic acid (RNA) interference and anti-inflammatory therapies.