Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs

Abstract

Since their introduction, statin (HMG-CoA reductase inhibitor) drugs have advanced the practice of cardiology to unparalleled levels. Even so, coronary heart disease (CHD) still remains the leading cause of death in developed countries, and is predicted to soon dominate the causes of global mortality and disability as well. The currently available non-statin drugs have had limited success in reversing the burden of heart disease, but new information suggests they have roles in sizeable subpopulations of those affected. In this review, the status of approved non-statin drugs and the significant potential of newer drugs are discussed. Several different ways to raise plasma high-density lipoprotein (HDL) cholesterol (HDL-C) levels have been proposed, but disappointments are now in large part attributed to a preoccupation with HDL quantity, rather than quality, which is more important in cardiovascular (CV) protection. Niacin, an old drug with many antiatherogenic properties, was re-evaluated in two imperfect randomized controlled trials (RCTs), and failed to demonstrate clear effectiveness or safety. Fibrates, also with an attractive antiatherosclerotic profile and classically used for hypertriglyceridemia, lacks evidence-based proof of efficacy, save for a subgroup of diabetic patients with atherogenic dyslipidemia. Omega-3 fatty acids fall into this category as well, even with an impressive epidemiological evidence base. Omega-3 research has been plagued with methodological difficulties yielding tepid, uncertain, and conflicting results; well-designed studies over longer periods of time are needed. Addition of ezetimibe to statin therapy has now been shown to decrease levels of low-density lipoprotein (LDL) cholesterol (LDL-C), accompanied by a modest decrease in the number of CV events, though without any improvement in CV mortality. Importantly, the latest data provide crucial evidence that LDL lowering is central to the management of CV disease. Of drugs that inhibit cholesteryl ester transfer protein (CETP) tested thus far, two have failed and two remain under investigation and may yet prove to be valuable therapeutic agents. Monoclonal antibodies to proprotein convertase subtilisin/kexin type 9, now in phase III trials, lower LDL-C by over 50 % and are most promising. These drugs offer new ability to lower LDL-C in patients in whom statin drug use is, for one reason or another, limited or insufficient. Mipomersen and lomitapide have been approved for use in patients with familial hypercholesterolemia, a more common disease than appreciated. Anti-inflammatory drugs are finally receiving due attention in trials to elucidate potential clinical usefulness. All told, even though statins remain the standard of care, non-statin drugs are poised to assume a new, vital role in managing dyslipidemia.

Current Treatment of Dyslipidemia: A New Paradigm for Statin Drug Use and the Need for Additional Therapies

“…While statins will certainly remain a mainstay of therapy, patients need additional and more potent agents, and their physicians need greater choice in order to individualize treatment and optimize patient outcomes. Ongoing collaboration between industry, researchers, and clinicians now present a number of promising agents, many with great appeal, as discussed in a sister paper published in this issue [80].…”

“…Another argument made against LDL targets was that, since the new ACC/AHA Cholesterol Guidelines found no benefit from adding any agent to statins while treating dyslipidemia, there was no point in pursuing targets [79]. Since the results of IMPROVE-IT demonstrated efficacy of ezetimibe in improving outcomes, and the approval of PCSK9 inhibitors capable of lowering LDL-C to levels below 1.2 mmol/L (50 m/dL) is imminent, on-treatment LDL-C levels now assume new importance [80].…”

“…At the time of writing, since there were no acceptable, compelling RCTs, no non-statin drugs were considered. The IMPROVE-IT results change this view [80]. An update is planned to address some issues of importance, based on data published since 2013.…”

Dietary chia seeds (Salvia hispanica) improve acute dyslipidemia and steatohepatitis in rats

“…Although there are various drugs to treat dyslipidemia (Kones & Rumana, ), available effective therapies for NAFLD/NASH are neither enough nor verified (Filozof, Goldstein, Williams, & Sanyal, ; Ishitobi et al, ; Ogawa et al, ). Currently, there is a growing use of functional foods and nutraceuticals, which contain proteins, polyphenols, dietary fiber, phytosterols, and long‐chain polyunsaturated fatty acids (PUFAs), as promising co‐adjuvants in the pharmacological therapy of dyslipidemia, NAFLD, and NASH (Chen, Wang, Zhang, & Yang, ; Hunter & Hegele, ; Lyu et al, ; Waltenberger, Mocan, Šmejkal, Heiss, & Atanasov, ).…”

Nutrition Studies, Optimum Cardiovascular Health, and Coronary Atherosclerosis-Ensuring A Solid Foundation for Public Policy

“…Greater statin use may account for plaque stabilization in the latter, due to lipid-lowering, anti-inflammatory, and other pleiotropic actions. In this regard, it should be mentioned that even in the current era of statin therapy, however, there is considerable on-treatment residual risk that remains unaddressed [38,39].…”