Background: Statin therapy effectively prevents vascular disease, but treatment targets are often not achieved.
Purpose: To compare the benefits and harms of high-dose statin monotherapy with those of combination therapy in adults at high risk for coronary disease.
Data Sources: English-language records from MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and the Cochrane Library (third quarter of 2008).
Study Selection: A reviewer screened records, and a second reviewer verified selection of randomized, controlled trials in adult patients that compared combinations of statins and bile-acid sequestrants, fibrates, ezetimibe, niacin, or Ï‰-3 fatty acids with statin monotherapy, as well as nonrandomized comparative studies that were longer than 24 weeks and reported clinical and harms outcomes.
Data Extraction: Data were abstracted for studies by using standardized forms, and study quality was rated with a standardized scale and strength of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation approach.
Data Synthesis: 102 studies met eligibility criteria. The main analysis compared combination therapy with high-dose statin monotherapy in high-risk patients. Very-low-strength evidence showed that statinâ€“ezetimibe (2 trials; nÂ = 439) and statinâ€“fibrate (1 trial; nÂ = 166) combinations did not reduce mortality more than high-dose statin monotherapy. No trials compared the effect of combination therapy versus high-dose statin monotherapy on the incidence of myocardial infarction, stroke, or revascularization procedures. Two statinâ€“ezetimibe trials (nÂ = 295) demonstrated higher low-density lipoprotein cholesterol goal attainment with combination therapy (odds ratio, 7.21 [95% CI, 4.30 to 12.08]). Trials in lower-risk patients did not show a difference in mortality.
Limitations: Studies were generally short, focused on surrogate outcomes, and were heterogeneous in the sample's risk for coronary disease. Few studies examined treatment combinations other than statinâ€“ezetimibe.
Conclusion: Limited evidence suggests that combinations of lipid-lowering agents do not improve clinical outcomes more than high-dose statin monotherapy. Very-low-quality evidence favors statinâ€“ezetimibe treatment for attainment of low-density lipoprotein cholesterol goals.
Primary Funding Source: Agency for Healthcare Research and Quality.