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Aspirin for Prevention of Stroke and Cardiovascular Events Among Patients With Peripheral Artery Disease

Hisato Takagi, MD, PhD; Takuya Umemoto, MD, PhD
JAMA. 2009;302(11):1165-1166. doi:10.1001/jama.2009.1325
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To the Editor: Dr Berger and colleagues1 conducted a meta-analysis investigating aspirin for prevention of cardiovascular events in patients with peripheral arterial disease (PAD). They found that treatment with aspirin alone or with dipyridamole in patients with PAD resulted in a statistically nonsignificant decrease in cardiovascular events and a statistically significant reduction in nonfatal stroke. Although funnel plots were reportedly generated for cardiovascular events, the authors did not assess publication bias for nonfatal stroke.

In the subset of 6 randomized controlled trials of aspirin alone (including trials in which either the treatment or control group did not have any events, but excluding trials in which both groups had no events), aspirin was associated with a significant reduction in nonfatal stroke (pooled relative risk [RR], 0.64; 95% confidence interval [CI], 0.42-0.99). To assess the effect of possible publication bias, we recommend using a trim and fill adjustment.2 This is an iterative nonparametric adjustment method based on a rank-based data augmentation technique to account for asymmetry on the funnel plot.3 If the conclusion of the meta-analysis remains unchanged following adjustment for the publication bias, the results can be considered reasonably robust, excluding publication bias.4 Publication or related biases can be common within meta-analyses, and researchers should routinely check whether conclusions of systematic reviews are robust to possible nonrandom selection mechanisms.5

AUTHOR INFORMATION

Financial Disclosures: None reported.

REFERENCES

Berger JS, Krantz MJ, Kittelson JM, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials.  JAMA. 2009;301(18):1909-1919
PubMedCrossRef
Duval S, Tweedie R. Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis.  Biometrics. 2000;56(2):455-463
PubMedCrossRef
Moreno SG, Sutton AJ, Ades AE,  et al.  Assessment of regression-based methods to adjust for publication bias through a comprehensive simulation study.  BMC Med Res Methodol. 2009;92
PubMedCrossRef
Souza JP, Pileggi C, Cecatti JG. Assessment of funnel plot asymmetry and publication bias in reproductive health meta-analyses: an analytic survey.  Reprod Health. 2007;43
PubMedCrossRef
Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses.  BMJ. 2000;320(7249):1574-1577
PubMedCrossRef

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Berger JS, Krantz MJ, Kittelson JM, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials.  JAMA. 2009;301(18):1909-1919
PubMedCrossRef
Duval S, Tweedie R. Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis.  Biometrics. 2000;56(2):455-463
PubMedCrossRef
Moreno SG, Sutton AJ, Ades AE,  et al.  Assessment of regression-based methods to adjust for publication bias through a comprehensive simulation study.  BMC Med Res Methodol. 2009;92
PubMedCrossRef
Souza JP, Pileggi C, Cecatti JG. Assessment of funnel plot asymmetry and publication bias in reproductive health meta-analyses: an analytic survey.  Reprod Health. 2007;43
PubMedCrossRef
Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses.  BMJ. 2000;320(7249):1574-1577
PubMedCrossRef
September 16, 2009
John M. Kittelson, PhD; Mori J. Krantz, MD; William R. Hiatt, MD
JAMA. 2009;302(11):1165-1166.
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