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.
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.
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.
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:
Bile acid sequestrants (BAS)
There was moderate SOE from four trials that a low-potency statin combined with a BAS lowered LDL-c up to 14 percent more than mid-potency statin monotherapy.
Moderate SOE from 11 trials favors mid-potency statin with ezetimibe for lowering LDL-c, with reduction up to 18 percent more compared to high-potency statin monotherapy among general populations. Low SOE from 11 trials favors mid-potency statin with ezetimibe for raising HDL-c, with increase up to 6 percent more compared to high-potency statin monotherapy.
There is insufficient evidence to compare combination therapy with fibrate and statin to intensification of statin monotherapy regardless of statin potency.
There is insufficient evidence to compare combination therapy with niacin and statin to intensification of statin monotherapy on lowering LDL-c, regardless of statin potency. Moderate SOE from three trials found that low-potency statin with niacin raises HDL-c up to 27 percent more than mid-potency statin monotherapy.
Omega-3 fatty acids
No relevant trials were found.
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.
Gudzune KA, Monroe AK, Sharma R, et al. Effectiveness of Combination Therapy With Statin and Another Lipid-Modifying Agent Compared With Intensified Statin Monotherapy: A Systematic Review. Annals of Internal Medicine. 2014 Feb 11. (Epub ahead of print] doi:10.7326/M13-2526