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

Gudzune et al., 2014 | Ann Intern Med | Systematic Review

Citation

Gudzune Kimberly A, Monroe Anne K, ... Robinson Karen A. Effectiveness of combination therapy with statin and another lipid-modifying agent compared with intensified statin monotherapy: a systematic review. Ann Intern Med. 2014-Apr-01;160(7):468-76. doi:10.7326/M13-2526

Abstract

BACKGROUND: 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. PURPOSE: 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). DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to July 2013, with an updated MEDLINE search through November 2013. STUDY SELECTION: Randomized, controlled trials published in English. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. LIMITATION: Many trials had short durations and high attrition rates, lacked blinding, and did not assess long-term clinical benefits or harms. CONCLUSION: 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. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Key Findings

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. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Outcomes Measured

• Requires manual extraction

Population

MeSH Terms

• Anticholesteremic Agents
• Azetidines
• Bile Acids and Salts
• Cholesterol, LDL
• Coronary Artery Disease
• Drug Therapy, Combination
• Ezetimibe
• Fatty Acids, Omega-3
• Fibric Acids
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypercholesterolemia
• Medication Adherence
• Niacin
• Randomized Controlled Trials as Topic
• Risk Factors
• Treatment Outcome

Evidence Classification

• Level: Systematic Review
• Publication Types: Journal Article, Research Support, U.S. Gov't, P.H.S., Systematic Review
• Vertical: niacin

Provenance

• PMID: 24514899
• DOI: 10.7326/M13-2526
• PMCID: Not in PMC
• Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09