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Structured Abstract

Background

A substantial proportion of patients with cardiovascular diseases use dietary supplements in anticipation of benefit. This also poses risks of adverse events from supplement-drug interactions and nonadherence associated with polypharmacy.

Objectives

For supplements commonly used by patients with cardiovascular disease, we examined benefits, harms, and effects on cardiovascular drug pharmacokinetics of coadministration of dietary supplements with cardiovascular drugs. We also sought evidence regarding variability among subgroups, and of statistical interactions between supplements and drugs.

Data Sources

We searched MEDLINE®, Embase, the Cochrane Library, International Bibliographic Information on Dietary Supplements (IBIDS), and Allied and Complementary Medicine Database (AMED), as well as gray literature, from inception to September 2011.

Study Selection

Following a predefined protocol, two reviewers included experimental and observational studies comparing a supplement plus cardiovascular drug versus drug alone published in English or German; other languages were excluded due to concerns with study quality and applicability.

Data Extraction

One reviewer extracted data into a standardized electronic form, assessed study risk of bias, graded the strength of the body of evidence, and reported its applicability. Study risk of bias and strength of evidence regarding gradable outcomes were independently verified, as was a random 10 percent subset of all data.

Data Synthesis

Sixty-seven randomized controlled trials, two controlled clinical trials, and one observational study contributed evidence of limited validity in highly selected populations. Evidence was insufficient for all gradable clinical efficacy and harms outcomes (e.g., mortality, thrombotic events, serious adverse events) because there were few, small studies per supplement. One pragmatic trial in women showed no benefit from coadministering vitamin E with aspirin on a composite cardiovascular outcome. Evidence for most intermediate outcomes of efficacy was insufficient or of low strength and suggested no effect. Notable findings were incremental improvement of triglyceridemia with omega-3 fatty acid supplementation, stabilization of international normalized ratio with vitamin K added to warfarin therapy, and improved high-density lipoprotein cholesterol (HDL-C) with added garlic. Clinically nonsignificant or otherwise inconclusive changes were noted for pharmacokinetic outcomes.

Limitations

The evidence base principally consisted of underpowered short-term studies in selected populations, generally with moderate risk of bias.

Conclusions

Limitations of the evidence base precluded meaningful conclusions across most supplement-drug combinations. Low-strength evidence indicates benefits of omega-3 fatty acids, vitamin K, and garlic coadministration on specific intermediate outcomes. Evidence regarding harms was inconclusive. Care providers and researchers should query supplement use to improve care and to facilitate research regarding drug-supplement interactions.