Systematic Review: Comparative Effectiveness and Harms of Combination Therapy and Monotherapy for Dyslipidemia
- Mukul Sharma, MD, MSc;
- Mohammed T. Ansari, MBBS, MMedSc, MPhil;
- Ahmed M. Abou-Setta, MD, PhD;
- Karla Soares-Weiser, MD, PhD;
- Teik Chye Ooi, MBBS;
- Margaret Sears, PhD;
- Fatemeh Yazdi, MSc;
- Alexander Tsertsvadze, MD, MSc; and
- David Moher, PhD
- From the University of Ottawa, Clinical Epidemiology Program, Ottawa Hospital Research Institute, and Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada; Alberta Research Centre for Health Evidence, University of Alberta, Edmonton, Alberta, Canada; and Enhance Reviews, Kfar-Saba, Israel.
Abstract
Background:
Background: Statin therapy effectively prevents vascular disease, but treatment targets are often not achieved.
Purpose:
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:
Data Sources: English-language records from MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and the Cochrane Library (third quarter of 2008).
Study Selection:
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 ω-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 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:
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 statin–ezetimibe (2 trials; n = 439) and statin–fibrate (1 trial; n = 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 statin–ezetimibe trials (n = 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:
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 statin–ezetimibe.
Conclusion:
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 statin–ezetimibe treatment for attainment of low-density lipoprotein cholesterol goals.
Primary Funding Source:
Primary Funding Source: Agency for Healthcare Research and Quality.
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