The Need for Combination Drug Therapies in Patients with Complex Dyslipidemia

Abstract

Statins are first line therapy for the prevention of cardiovascular disease (CVD). Only 30 %-70 % of high risk patients will attain standard low-density lipoprotein cholesterol targets. Patients with familial hypercholesterolemia and genetic mixed hyperlipidemias do not meet goals with standard therapy. Patients with mixed hyperlipidemia secondary to the metabolic syndrome, diabetes, renal, or HIV infection are at high residual risk due to low HDL-cholesterol or high triglycerides. Newer therapies can be added to statins. The use of ezetimibe has CVD outcomes evidence in chronic renal disease. Adding omega-3 fatty acids, fibrates, or niacin to statins has failed to show any benefit except possibly with fibrates in patients with diabetes and low HDL-C/high triglycerides. Additional benefits on lipid profiles have been shown with pro-protein convertase subtilisin/kexin-9 (PCSK9), mipomersen, lomitapide, and cholesterol ester transfer protein inhibitors (CETPIs). Two CETPIs have failed to show benefit in hard outcomes trials but others remain under investigation. It remains unclear whether additional therapies add to statins for the prevention of CVD in most patients. They may have some added benefit in patients with complex dyslipidemias.

A Systems Biology Approach for Identifying Hepatotoxicant Groups Based on Similarity in Mechanisms of Action and Chemical Structure

“…Clofibrate and gemfibrozil are PPARA agonists, while simvastatin, a statin compound, increases expression of PPARA and as such can have a similar effect [39]. Indeed there appears to be a cross-talk of statin signaling pathways and (agonist-induced) PPARA activity, and combination therapies of fibrates and statins are being used to treat dyslipidemia [40][41][42]. Valproic acid has a different mechanism of action and is used as an anticonvulsant and mood-stabilizing drug which has been attributed to the blockade of voltage-dependent sodium channels and increased brain levels of gamma-aminobutyric acid (GABA) [43].…”

A new phenotypic classification system for dyslipidemias based on the standard lipid panel

“…Identifying such patients by lipoprotein phenotyping, followed by specific and appropriate treatment can reduce the incidence of acute pancreatitis [ 49 ] In case of Type I, referral to a nutritionist is important because adherence to a strict low-fat diet is challenging but often necessary as pharmacotherapy often does not add much benefit when lipoprotein lipase activity is very low or nonexistent [ 34 ]. Because of the high incidence of ASCVD in patients with Type IIa, IIb, and III phenotypes [ 12 , 33 ], and their frequent need for combination pharmacotherapy [ 50 ], many of these patients should be seen by a lipid specialist, particularly if they do not show a good response to initial therapy. Type VI patients should not only be referred to a lipid specialist but also to a nutritionist for instructions on a low-fat diet and for high-dose fat soluble vitamin supplementation.…”

“…Lifestyle modifications should also be recommended [ 25 , 26 , 54 ]. For many patients with Type I and some V patients, a very low-fat diet is often an essential part of therapy [ 50 , 54 ]. Gene therapy for LPL deficiency was approved in Europe, but it is no longer available [ 55 ].…”

Primary Prevention of Atherosclerotic Cardiovascular Disease

“…The additional effect of ezetimibe in combination with statin therapy on cardiovascular outcomes for the general population remains inconclusive; however, clinical study with this agent is ongoing. 41-45 Health care providers should be familiar with the differential effects on lipoprotein levels and side effects of nonstatin therapeutic agents to effectively maximize the potential benefit and minimize the risks associated with drug therapy.…”