Statins: Monotherapy or Combination Strategy for the Treatment of Dyslipidemia

Abstract

Statins are the drug of first choice for the treatment of most dyslipidemias. They have excellent efficacy in reducing the concentration of low-density lipoprotein cholesterol (LDL-C) and have been proven to reduce the incidence of cardiovascular events, although differences exist in the lipid-modifying properties of these agents. Combination therapy may be considered for patients who do not achieve their lipid goal despite optimization of statin treatment. In severely hypercholesterolemic patients, combinations of statins with bile acid sequestrants, plant sterols or specific cholesterol absorption inhibitors may provide additional reductions in LDL-C and extend the therapeutic options in these difficult-to-treat patients. In patients with mixed dyslipidemias, combination of a statin with niacin or a fibrate may be necessary to fully correct lipid abnormalities. Although these combinations may be associated with an increased incidence of adverse effects, particularly myopathy and hepatotoxicity, recent clinical trials suggest that the benefit of enhanced efficacy across the lipid profile out weighs the risk of toxicity. Nevertheless, statin-niacin or statin-fibrate combinations should only be considered after careful risk-benefit assessment, and patients should be well informed of potential side effects. Doses of each drug should be kept to a minimum in order to reduce the risk of adverse effects. Combination treatment with statins and fish oil has shown promising improvements in several lipid parameters without an increase in systemic toxicity, and this combination may be a useful addition to the options available for treatment of refractory patients who cannot tolerate statin-niacin or statin-fibrate combinations.

Lipid Management Strategies for the Prevention of Adverse Cardiovascular Events

“…Of nearly 5,000 patients with dyslipidemia stratified into risk categories for CAD or established CAD, only 38% reached target National Cholesterol Education Program levels, and success rates in achieving target levels were lowest in those with known CAD. Similar success rates in the treatment of dyslipidemic patients in Europe have been shown [2]. Such findings underscore the need for more aggressive treatment of dyslipidemia and the identification of those at high risk for cardiovascular morbidity who would most benefit from such treatment.…”

“…Twelve cases of myopathic reactions, including rhabdomyolysis and renal failure, were reported from 1987 to 1988 with the use of a combination of lovastatin and gemfibrozil [8]. However, as Carmena [2] points out, subsequent review of multiple studies with 11,600 patients examining the safety and efficacy of statin-fibrate combination therapy has not shown any cases of rhabdomyolysis or renal failure and a much lower incidence of myopathy (0.12%) than early studies suggested.…”

“…While many patients may achieve the lipid profile goals outlined by the National Cholesterol Education Program Adult Treatment Panel III (ATP III) with statin therapy alone, some require the addition of further pharmacologic agents to control abnormal lipids and reduce the incidence of cardiovascular events. In a review of statins as monotherapy and as part of combination treatment, Carmena [2] highlights current and future options for lipid-lowering agents as well as their efficacy and safety profiles.…”

“…In those patients unable to achieve target LDL cholesterol levels with maximal (or maximally tolerated) doses of statins, newer agents, including colesevelam, plant sterols and ezetimibe, appear to be effective and safe adjuncts to further lower LDL [2]. Several studies recently presented at the American College of Cardiology Scientific Sessions investigating the efficacy of ezetimibe in combination with statin drugs showed significantly reduced LDL levels compared to statin monotherapy, with safety profiles similar to statins alone or placebo [9][10][11].…”

Apolipoprotein B and apolipoprotein A‐I: risk indicators of coronary heart disease and targets for lipid‐modifying therapy

“…Statin monotherapy is generally well tolerated except for the severe complications induced by cerivastatin used at high doses or in combination with gemfibrozil, which resulted in its withdrawal [162]. Indeed, recent clinical trials suggest that the benefits of enhanced efficacy across the lipid profile outweigh the risk of toxicity when consideration is given to the choice of agents to be combined and doses are kept as low as possible [163]. As statins have also been shown to be effective in improving the apolipoprotein profile, they will most likely be the basic treatment upon which other lipid‐lowering or other cardioprotective agents are added.…”