Objective: To assess the benefits and harms of combination of statin and other lipid-modifying medication compared to intensification of statin monotherapy. This is an update to a 2009 review.
Data sources: The search for the prior review included MEDLINE® from 1966 to May 2009, Embase® from 1980 to May 2009, and the Cochrane Library to the third quarter of 2008. Additional searches of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from May 2008 to July 2013 were conducted for the update.
Review methods: Paired investigators independently screened search results to assess eligibility. Investigators abstracted data sequentially and assessed risk of bias independently. Investigators graded the strength of evidence (SOE) as a group.
Results: All evidence for clinical outcomes (mortality, acute coronary events, and revascularization procedures) were graded as insufficient when comparing lower potency combination therapy with higher potency statin monotherapy. Results of effects on surrogates—low-density lipoprotein (LDL-c) and high-density lipoprotein (HDL-c)— and on serious adverse events are summarized below:
Conclusions: Although many studies looked at intermediate outcomes, few studies addressed the question of which approach produces better clinical outcomes. Combination of statin with ezetimibe or bile acid sequestrant lowered LDL-c better than intensification of statin monotherapy, but evidence for clinical outcomes (mortality, acute coronary events, and revascularization procedures) was insufficient across all potency comparisons for all combination therapy regimens. Additional studies evaluating long-term clinical benefits and harms are needed to better inform clinical decisionmaking, patient choice, and clinical practice guidelines.