Importance: Niacin remains a therapeutic option for patients with cardiovascular disease, but recent studies have called into question the effectiveness of other drugs that increase high-density lipoprotein cholesterol levels.

Objective: To systematically review and evaluate the evidence supporting current US Food and Drug Administration-approved uses of niacin in cardiovascular disease prevention settings.

Data sources: MEDLINE, Embase, Cochrane Controlled Clinical Trial Register (Central), ClinicalTrials.gov, and TrialResults-center, from database inception to October 2017.

Study selection: The systematic review included clinical trials involving niacin as a treatment for cardiovascular disease. The meta-analysis included randomized clinical trials reporting niacin's effect, as exposure, on at least 1 long-term cardiovascular disease outcome.

Data extraction and synthesis: Aggregate study-level data were extracted between November 2017 and January 2018 by 3 independent reviewers, and the analysis was performed in February 2018. Inverse-variance weighted methods were used to produce pooled risk ratios using random-effects models for between-study heterogeneity. Random effects-weighted metaregression analysis was used to assess the association of change in high-density lipoprotein cholesterol levels with the log risk ratio of the pooled results.

Main outcomes and measures: Cardiovascular disease, coronary heart disease mortality, and other cardiovascular events, including acute coronary syndrome, fatal and nonfatal stroke, revascularization, and major adverse cardiac events.

Results: Of 119 clinical trials, 17 documented niacin's effect on at least 1 cardiovascular disease outcome. The meta-analysis included 35 760 patients with histories of cardiovascular disease or dyslipidemia. Cumulative evidence found no preventive association of niacin with cardiovascular outcomes in secondary prevention. Stratified meta-analysis showed an association of niacin monotherapy with reduction of some cardiovascular events among patients without statin treatment (acute coronary syndrome: relative risk, 0.74; 95% CI, 0.58-0.96; stroke: relative risk, 0.74; 95% CI, 0.59-0.94; revascularization: relative risk, 0.51; 95% CI, 0.37-0.72). These results were mainly derived from 2 trials conducted in the 1970s and 1980s.

Conclusions and relevance: Niacin may have some use in lipid control for secondary prevention as monotherapy, perhaps in patients intolerant to statins, but evidence is from older studies on a population potentially not representative of current-day patients.