Annals of internal medicine

Effectiveness of combination therapy with statin and another lipid-modifying agent compared with intensified statin monotherapy: a systematic review.

PMID 24514899


Some patients do not tolerate or respond to high-intensity statin monotherapy. Lower-intensity statin combined with nonstatin medication may be an alternative, but the benefits and risks compared with those of higher-intensity statin monotherapy are unclear. To compare the clinical benefits, adherence, and harms of lower-intensity statin combination therapy with those of higher-intensity statin monotherapy among adults at high risk for atherosclerotic cardiovascular disease (ASCVD). MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to July 2013, with an updated MEDLINE search through November 2013. Randomized, controlled trials published in English. Two reviewers extracted information on study design, population characteristics, interventions, and outcomes (deaths, ASCVD events, low-density lipoprotein [LDL] cholesterol level, adherence, and adverse events). Two independent reviewers assessed risk of bias. A total of 36 trials were included. Low-intensity statin plus bile acid sequestrant decreased LDL cholesterol level 0% to 14% more than mid-intensity monotherapy among high-risk hyperlipidemic patients. Mid-intensity statin plus ezetimibe decreased LDL cholesterol level 5% to 15% and 3% to 21% more than high-intensity monotherapy among patients with ASCVD and diabetes mellitus, respectively. Evidence was insufficient to evaluate LDL cholesterol for fibrates, niacin, and ω-3 fatty acids. Evidence was insufficient for long-term clinical outcomes, adherence, and harms for all regimens. Many trials had short durations and high attrition rates, lacked blinding, and did not assess long-term clinical benefits or harms. Clinicians could consider using lower-intensity statin combined with bile acid sequestrant or ezetimibe among high-risk patients intolerant of or unresponsive to statins; however, this strategy should be used with caution given the lack of evidence on long-term clinical benefits and harms. Agency for Healthcare Research and Quality.