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Longer- Versus Shorter-Duration Dual-Antiplatelet Therapy After Drug-Eluting Stent Placement: A Systematic Review and Meta-analysisDuration of Dual-Antiplatelet Therapy After Drug-Eluting Stents

Frederick A. Spencer, MD; Manya Prasad, MBBS; Per O. Vandvik, MD, PhD; Devin Chetan, HBA; Qi Zhou, PhD; and Gordon Guyatt, MD
[+] Article, Author, and Disclosure Information

This article was published online first at www.annals.org on 26 May 2015.


From McMaster University, Hamilton, Ontario, Canada; Pt. Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India; and Innlandet Hospital Trust, Gjøvik, Norway.

Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0083.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Requests for Single Reprints: Frederick A. Spencer, MD, Department of Medicine, McMaster University, Faculty of Health Sciences, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada; e-mail, fspence@mcmaster.ca.

Current Author Addresses: Dr. Spencer and Mr. Chetan: Department of Medicine, McMaster University, Faculty of Health Sciences, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.

Dr. Prasad: Department of Community Medicine, Pt. Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Medical Road, Maharishi Dayanand University, Rohtak, Haryana 124001, India.

Dr. Vandvik: Norwegian Knowledge Centre for the Health Services (The Knowledge Centre), PO Box 7004, St. Olavs Plass, N-0130 Oslo, Norway.

Drs. Zhou and Guyatt: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, Ontario L8S 4L8, Canada.

Author Contributions: Conception and design: G.H. Guyatt, F.A. Spencer, P.O. Vandvik.

Analysis and interpretation of the data: D. Chetan, G.H. Guyatt, M. Prasad, F.A. Spencer, P.O. Vandvik, Q. Zhou.

Drafting of the article: F.A. Spencer, P.O. Vandvik.

Critical revision for important intellectual content: D. Chetan, G.H. Guyatt, M. Prasad, P.O. Vandvik.

Final approval of the article: D. Chetan, G.H. Guyatt, M. Prasad, F.A. Spencer, P.O. Vandvik, Q. Zhou.

Statistical expertise: Q. Zhou.

Collection and assembly of data: D. Chetan, M. Prasad, F.A. Spencer.


Ann Intern Med. 2015;163(2):118-126. doi:10.7326/M15-0083
Text Size: A A A

Background: The appropriate duration of dual-antiplatelet therapy (DAPT) after drug-eluting stent (DES) placement remains controversial.

Purpose: To summarize data on clinical outcomes with longer- versus shorter-duration DAPT after DES placement in adults with coronary artery disease.

Data Sources: Ovid MEDLINE and EMBASE, 1996 to 27 March 2015, and manual screening of references.

Study Selection: Randomized, controlled trials comparing longer- versus shorter-duration DAPT after DES placement.

Data Extraction: Two reviewers screened potentially eligible articles; extracted data on populations, interventions, and outcomes; assessed risk of bias; and used the Grading of Recommendations Assessment, Development and Evaluation guidelines to rate overall confidence in effect estimates.

Data Synthesis: Among 1010 articles identified, 9 trials including 29 531 patients were eligible; data were complete for 28 808 patients. Moderate-quality evidence showed that longer-duration DAPT decreased risk for myocardial infarction (risk ratio [RR], 0.73 [95% CI, 0.58 to 0.92]) and increased mortality (RR, 1.19 [CI, 1.04 to 1.36]). High-quality evidence showed that DAPT increased risk for major bleeding (RR, 1.63 [CI, 1.34 to 1.99]).

Limitation: Confidence in estimates were decreased owing to imprecision for most outcomes (particularly myocardial infarction), risk of bias from limited blinding in 7 of 9 studies, indirectness due to variability in use of first- and second-generation stents, and off-protocol use of DAPT in some studies.

Conclusion: Extended DAPT is associated with approximately 8 fewer myocardial infarctions per 1000 treated patients per year but 6 more major bleeding events than shorter-duration DAPT. Because absolute effects are very small and closely balanced, decisions regarding the duration of DAPT therapy must take into account patients' values and preference.

Primary Funding Source: None.

Figures

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Appendix Figure 1.

Summary of evidence search and selection.

* Records were identified using Ovid MEDLINE and EMBASE (1996 to 27 March 2015).

† Data from a later manuscript were used.

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Appendix Figure 2.

Assessment of risk of bias.

See the legend for Figure 1 for abbreviation expansions. A green circle with a plus sign means no risk of bias; a red circle with a minus sign means potential risk of bias.

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Figure 1.

Pooled risk for death with longer- versus shorter-duration DAPT after placement of a drug-eluting stent.

ARCTIC-Interruption = Assessment by a double Randomization of a Conventional antiplatelet strategy versus a monitoring-guided strategy for drug-eluting stent implantation and, of Treatment Interruption versus Continuation 1 year after stenting Interruption Study; DAPT = dual-antiplatelet therapy; DES LATE = Optimal Duration of Clopidogrel Therapy With Drug Eluting Stents to Reduce Late Coronary Arterial Thrombotic Event Study; EXCELLENT = Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting; ISAR-SAFE = Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting; ITALIC = Is There A Life for DES after Discontinuation of Clopidogrel; OPTIMIZE = Optimized Duration of Clopidogrel Therapy Following Treatment With the Zotarolimus-Eluting Stent in Real-World Clinical Practice Study; PRODIGY = Prolonging Dual Antiplatelet Treatment After Grading Stent- Induced Intimal Hyperplasia Study; SECURITY = Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy.

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Appendix Figure 3.

Pooled risk for cardiovascular death with longer- versus shorter-duration DAPT after placement of a drug-eluting stent.

See the legend for Figure 1 for abbreviation expansions.

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Figure 2.

Pooled risk for myocardial infarction with longer- versus shorter-duration DAPT after placement of a drug-eluting stent.

See the legend for Figure 1 for abbreviation expansions.

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Figure 3.

Pooled risk for myocardial infarction with longer- versus shorter-duration DAPT after placement of a drug-eluting stent: subset analysis stratified by timing of randomization.

See the legend for Figure 1 for abbreviation expansions.

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Figure 4.

Pooled risk for major bleeding with longer- versus shorter-duration DAPT after placement of a drug-eluting stent.

See the legend for Figure 1 for abbreviation expansions.

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Appendix Figure 4.

Pooled risk for major bleeding with longer- versus shorter-duration DAPT after placement of a drug-eluting stent: subset analysis stratified by timing of randomization.

See the legend for Figure 1 for abbreviation expansions.

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Appendix Figure 5.

Pooled risk for any stroke with longer- versus shorter-duration DAPT after placement of a drug-eluting stent.

See the legend for Figure 1 for abbreviation expansions.

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Appendix Figure 6.

Pooled risk for revascularization with longer- versus shorter-duration DAPT after placement of drug-eluting stent.

See the legend for Figure 1 for abbreviation expansions.

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