Bile acid sequestrants (BAS) and statins: the BAS have been shown to induce meaningful reductions in low-density lipoprotein cholesterol (LDL-C) and reduce risk of cardiovascular (CV) events; used either in monotherapy or in combination with other lipid lowering drugs have been shown to retard rates of atherosclerotic plaque progression and even induce plaque regression; in statin intolerant patients BAS may be combined with ezetimibe as needed; the BAS have a relatively favorable safety profile (however gastrointestinal adverse effects might be often present even at low doses, which limit their practical use), and their elimination is independent of hepatic and renal function [1];

Fibrates and statins: pharmacotherapy with fibrates should be considered in patients with the triglyceride (TG) level >2.3 mmol/L (200 mg/dL), in whom TG reduction could not be achieved through non-pharmacological treatment – exercise, weight reduction and diet; statins are the treatment of choice for moderate hypertriglyceridemia; fibrates should be recommended in the high risk group (including the one with diabetes), while in other patients the addition of fibrates to a statin should always be considered if statin monotherapy does not bring the satisfactory reduction in TG levels; hypertriglyceridemia-related acute pancreatitis is a clear indication for therapy with fibrates, as an adjunct to the right diet and omega fatty acids [2, 3];

Ezetimibe and statins: ezetimibe in monotherapy (e.g. in statin intolerant patients) or added to statin therapy reduces LDL-C level by additionally 20–25 %; the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) [4] with ezetimibe is the first proof of the concept that a non-statin LDL-lowering intervention further reduces CV risk to a similar extent as statin; however, even with ezetimibe on top of statin therapy unmet clinical need remains [5];

Niacin and statins: nicotinic acid (niacin) has been associated with increase in high density lipoprotein cholesterol (HDL-C) up to 30 % and reductions in LDL-C, total cholesterol (TC), TGs, small dense LDL particles, apolipoprotein B (apoB) and lipoprotein a [Lp(a)]; the addition of niacin to statins seems to improve the general lipid profile, however there has been no benefit in terms of CV prevention in the recent trials; an increase in serious adverse effects (AEs) was noted in the Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial [6] with niacin and laropiprant what further limits its practical use, and it was the reason that it is no longer on the market in many countries [7];

Omega–3 fatty acids and statins: omega-3 fatty acids (OM3 FAs) therapies added to optimal statin monotherapy is safe and well tolerated and reduces triglyceride-rich lipoproteins cholesterol (TRL-C)/non-HDL in subjects with hypertriglyceridemia; patients with elevated TGs may benefit from OM3 FAs supplementation as combination therapy to statins and lifestyle changes, especially those with TGs ≥500 mg/dL and perhaps, pending results of ongoing trials, those with TGs ≥200 and <500 mg/dL; additional roles for OM3 FAs lie in certain subgroups with specific familial dyslipidemias and those who do not tolerate statin therapy; the ongoing STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia (STRENGTH) and the Reduction of Cardiovascular Events With EPA – Intervention Trial (REDUCE-IT) are the first CV outcomes trials to appropriately target an elevated TG with a therapy that effectively lowers the atherogenic components of non-HDL that are not sufficiently managed by statin therapy alone [8];

Cholesteryl ester transfer protein (CETP) inhibitors and statins: despite an unfavorable history of clinical development with AEs of torcetrapib and no clinical benefit with dalcetrapib, the hope remains that potent CETP inhibitors (anacetrapib and evacetrapib) with favorable effects on both HDL and atherogenic lipoproteins, may prove to reduce CV events in ongoing clinical trials; the results of these trials will provide definitive information with regards to the efficacy and safety of this class in order to determine whether they will prove to be a useful adjunctive therapy in patients optimally treated with a statin [9];

Mipomersen and statins: mipomersen has complementary to statins mechanisms of action, as statins increase LDL catabolism and mipomersen inhibits apoB synthesis; the efficient dose-dependent reductions in plasma LDL-C concentrations achieved by mipomersen therapy is highly significant, however, the risk of hepatic steatosis and injection-site reactions continue to remain a concern that bear on the clinical use of this agent; despite the favorable effects of mipomersen on Lp(a), CV benefit of treating elevated Lp(a) remains untested; new formulations of mipomersen that do not cause injection-site reactions are essential to increase the acceptability of this form of therapy by patients [10];