Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Sep 17:347:f5307.
doi: 10.1136/bmj.f5307.

Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison

Joshua J Gagne  1 , Katsiaryana Bykov, Niteesh K Choudhry, Timothy J Toomey, John G Connolly, Jerry Avorn
Affiliations
Meta-Analysis

Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison

Joshua J Gagne et al. BMJ. .

Abstract

Objective: To evaluate whether smoking status is associated with the efficacy of antiplatelet treatment in the prevention of cardiovascular events.

Design: Systematic review, meta-analysis, and indirect comparisons.

Data sources: Medline (1966 to present) and Embase (1974 to present), with supplementary searches in databases of abstracts from major cardiology conferences, the Cumulative Index to Nursing and Allied Health (CINAHL) and the CAB Abstracts databases, and Google Scholar.

Study selection: Randomized trials of clopidogrel, prasugrel, or ticagrelor that examined clinical outcomes among subgroups of smokers and nonsmokers.

Data extraction: Two authors independently extracted all data, including information on the patient populations included in the trials, treatment types and doses, definitions of clinical outcomes and duration of follow-up, definitions of smoking subgroups and number of patients in each group, and effect estimates and 95% confidence intervals for each smoking status subgroup.

Results: Of nine eligible randomized trials, one investigated clopidogrel compared with aspirin, four investigated clopidogrel plus aspirin compared with aspirin alone, and one investigated double dose compared with standard dose clopidogrel; these trials include 74,489 patients, of whom 21,717 (29%) were smokers. Among smokers, patients randomized to clopidogrel experienced a 25% reduction in the primary composite clinical outcome of cardiovascular death, myocardial infarction, and stroke compared with patients in the control groups (relative risk 0.75, 95% confidence interval 0.67 to 0.83). In nonsmokers, however, clopidogrel produced just an 8% reduction in the composite outcome (0.92, 0.87 to 0.98). Two studies investigated prasugrel plus aspirin compared with clopidogrel plus aspirin, and one study investigated ticagrelor plus aspirin compared with clopidogrel plus aspirin. In smokers, the relative risk was 0.71 (0.61 to 0.82) for prasugrel compared with clopidogrel and 0.83 (0.68 to 1.00) for ticagrelor compared with clopidogrel. Corresponding relative risks were 0.92 (0.83 to 1.01) and 0.89 (0.79 to 1.00) among nonsmokers.

Conclusions: In randomized clinical trials of antiplatelet drugs, the reported clinical benefit of clopidogrel in reducing cardiovascular death, myocardial infarction, and stroke was seen primarily in smokers, with little benefit in nonsmokers.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

None
Fig 1 Flow of identification and inclusion of studies of antiplatet drugs
None
Fig 2 Efficacy of clopidogrel stratified by baseline smoking status. *Cumulative incidences in each treatment arm were not reported within smoking subgroups in CHARISMA trial. †Cumulative incidences presented here for CURE trial are only for never smokers. Cumulative incidences for former smokers were 10.3% in clopidogrel arm and 13.1% in control arm
None
Fig 3 Hazard ratios for clopidogrel, prasugrel, ticagrelor, and controls in mixed treatment comparisons. Solid lines indicate estimates based on direct comparisons between two treatments. Dashed lines indicate estimates derived from indirect comparisons
See this image and copyright information in PMC

Comment in

References

    1. Bowry AD, Brookhart MA, Choudhry NK. Meta-analysis of the efficacy and safety of clopidogrel plus aspirin as compared to antiplatelet monotherapy for the prevention of vascular events. Am J Cardiol 2008;101:960-6. - PubMed
    1. Gurbel PA, Nolin TD, Tantry US. Clopidogrel efficacy and cigarette smoking status. JAMA 2012;307:2495-6. - PubMed
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535. - PMC - PubMed
    1. Higgins JPT, Altman DG, Sterne JAC. Assessing risk of bias in included studies. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Collaboration, 2011.
    1. Sabatine MS, McCabe CH, Gibson CM, Cannon CP. Design and rationale of clopidogrel as adjunctive reperfusion therapy-thrombolysis in myocardial infarction (CLARITY-TIMI) 28 trial. Am Heart J 2005;149:227-33. - PubMed

Publication types

MeSH terms

Substances