Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk

Abstract

Although statin therapy represents a cornerstone of cardiovascular disease (CVD) prevention, a major residual CVD risk (60-70% of total relative risk) remains, attributable to both modifiable and non-modifiable risk factors. Among the former, low levels of HDL-C together with elevated triglyceride (TG)-rich lipoproteins and their remnants represent major therapeutic targets. The current pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately associated with an atherogenic dyslipidemic phenotype featuring low HDL-C combined with elevated TG-rich lipoproteins and small dense LDL. In this context, there is renewed interest in pharmacotherapeutic strategies involving niacin and fibrates in monotherapy and in association with statins. This comprehensive, critical review of available data in dyslipidemic subjects indicates that niacin is more efficacious in raising HDL-C than fibrates, whereas niacin and fibrates reduce TG-rich lipoproteins and LDL comparably. Niacin is distinguished by its unique capacity to effectively lower Lp(a) levels. Several studies have demonstrated anti-atherosclerotic action for both niacin and fibrates. In contrast with statin therapy, the clinical benefit of fibrates appears limited to reduction of nonfatal myocardial infarction, whereas niacin (frequently associated with statins and/or other agents) exerts benefit across a wider range of cardiovascular endpoints in studies involving limited patient numbers. Clearly the future treatment of atherogenic dyslipidemias involving the lipid triad, as exemplified by the occurrence of the mixed dyslipidemic phenotype in metabolic syndrome, type 2 diabetes, renal, and auto-immune diseases, requires integrated pharmacotherapy targeted not only to proatherogenic particles, notably VLDL, IDL, LDL, and Lp(a), but also to atheroprotective HDL.