Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention
Open accessAbstract
IMPORTANCE: Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding. OBJECTIVE: To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI. DESIGN, SETTING, AND PARTICIPANTS: Among 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014). EXPOSURES: Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin. MAIN OUTCOMES AND MEASURES: Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI. RESULTS: Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding. CONCLUSION AND RELEVANCE: Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00977938.
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Type 2 diabetes is linked to a generalized prothrombotic state caused by altered coagulation and platelet function.
“Among the factors contributing to an elevated cardiovascular risk in patients with T2DM is a generalized prothrombotic state23,24 attributable to altered coagulation and platelet function”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [23]
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- Authors
- Yeh, R. W., Secemsky, E. A., Kereiakes, D. J., Normand, S.-L. T., Gershlick, A. H., Cohen, D. J., Spertus, J. A., Steg, P. G., Cutlip, D. E., Rinaldi, M. J., Camenzind, E., Wijns, W., Apruzzese, P. K., Song, Y., Massaro, J. M., Mauri, L., & for the DAPT Study Investigators
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Christ Hospital (US)
- University of Leicester (GB)
- Saint Luke's Hospital (US)
- Washington University in St. Louis (US)
- Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Paris, France14Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique, Hôpitaux de Paris, Paris, France15National Heart and Lung Institute, Institute of Card
- Carolinas Healthcare System (US)
- Centre Hospitalier Régional et Universitaire de Nancy (FR)
- Onze Lieve Vrouwziekenhuis Hospital (BE)
- Boston University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Yeh, Robert W.
- Mauri, Laura
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2016-04-26
- Volume
- 315
- Issue
- 16
- Pages
- 1735
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5408574
- OpenAlex
- W2324839838
- Cited by
- 934
- References
- 19
- Citations by year
- 2026: 38 · 2025: 50 · 2024: 55 · 2023: 80 · 2022: 90 · 2021: 102 · 2020: 113 · 2019: 102 · 2018: 116 · 2017: 130 · 2016: 57
- FWCI
- 111.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Ohio State University
- Wake Forest University
- Creighton University
- Foundation for Cardiovascular Research
- University of Pittsburgh
- University of Oklahoma
- University of Cincinnati
- CSL Behring
- Boston Scientific Corporation
- Thomas Jefferson University
- Regeneron Pharmaceuticals
- Temple University
- Amarin Corporation
- Medicines Company
- ReCor Medical
- Heart Research Institute
- Daiichi-Sankyo
- Servier
- MicroPort
- Stony Brook University
- U.S. Food and Drug Administration (R01 FD003870)
- University of Illinois at Urbana-Champaign
- Medical Center, University of Pittsburgh
- Abbott Vascular
- National Heart, Lung, and Blood Institute (K23HL118138)
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- dual antiplatelet therapy, percutaneous coronary intervention, prediction rules, ischemia, hemorrhage, thienopyridines, aspirin, stent thrombosis, myocardial infarction, risk stratification, paclitaxel-eluting stents, PROTECT trial, clinical decision tool, bleeding risk, ischemic risk, diabetes mellitus, congestive heart failure
- MeSH terms
- Age Factors, Aged, Antineoplastic Agents, Phytogenic, Aspirin, Diabetes Mellitus, Female, Hemorrhage, Humans, Ischemia, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Pyridines, Risk Factors, Smoking, Thrombosis, Time Factors, Linear Models, Paclitaxel, Risk Assessment, Drug-Eluting Stents, Percutaneous Coronary Intervention
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