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Clinician Article

Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials.



  • Palmerini T
  • Benedetto U
  • Bacchi-Reggiani L
  • Della Riva D
  • Biondi-Zoccai G
  • Feres F, et al.
Lancet. 2015 Jun 13;385(9985):2371-82. doi: 10.1016/S0140-6736(15)60263-X. Epub 2015 Mar 14. (Review)
PMID: 25777667
Read abstract Read evidence summary
Disciplines
  • Internal Medicine
    Relevance - 7/7
    Newsworthiness - 6/7
  • Cardiology
    Relevance - 6/7
    Newsworthiness - 6/7
  • Hematology
    Relevance - 5/7
    Newsworthiness - 7/7
  • Hemostasis and Thrombosis
    Relevance - 5/7
    Newsworthiness - 7/7

Abstract

BACKGROUND: Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies.

METHODS: We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches.

FINDINGS: We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31,666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT.

INTERPRETATION: Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality.

FUNDING: None.


Clinical Comments

Cardiology

As a practicing cardiologist, I find this information very thought-provoking. Many post-PCI patients are kept on Plavix for much too long.

Hematology

At my institution (and many others with which I am familiar), interventional cardiologists make decisions in this area -- hematologists get involved only in a minority of unusual cases. I found this report very interesting, but our cardiologists are the ones who have the expertise to fully interpret the findings.

Internal Medicine

The long-term follow-up of dual antiplatelets often falls to non-cardiologists as comorbidities, events, and other medications require oversight. The optimal duration of DAPT for drug-eluting and bare-metal stents is a constant source of frustration due to lack of well validated clinical prediction rules of benefit vs harm.

Internal Medicine

Good meta-analysis of long-term dual antiplatelet therapy, even though it is now recommended for only 1 year. It is good to know that all-cause mortality is higher with longer therapy.

Internal Medicine

This is an important issue. What I don't know is whether this analysis supports their conclusion. This needs to be carefully looked at by an experienced methodologist to make sure the data support the conclusion.

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