Bleeding After Initiation of Multiple Antithrombotic Drugs, Including Triple Therapy, in Atrial Fibrillation Patients Following Myocardial Infarction and Coronary Intervention: A Nationwide Cohort Study
Abstract
Background—: Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment. Methods and Results—: Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90–360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40). Conclusions—: High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.
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Approximately 15% of AF patients in contemporary trials and registries have a history of myocardial infarction.
“Approximately 15% of AF patients in contemporary trials 513 and registries [514][515][516] have a history of myocardial 1498 infarction.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [515]
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“Similar to WOEST, larger patient registries including N11,000 patients have also shown that triple therapy increases the risk for bleeding with no benefit on the number of ischemic events.(14) Risk factors summarized in the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years,”
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“Yet, combining OAC and DAPT is associated with increased bleeding [71].”
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“The group did not find a significant benefit for the combined thromboembolic endpoint of cardiovascular death, myocardial infarction (MI), and ischaemic stroke for TT in comparison with VKA plus a single antiplatelet drug (HR 1.15 [0.95; 1.40]) in patients with atrial fibrillation after MI/percutaneous coronary interv…”
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“Triple therapy consequently seems the best option but has been associated with major bleeding rates as high as 7% at one year (18-20).”
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“To date, few populational studies have explicitly quantified the association between the concurrent use of different antithrombotic therapies and the risk of bleeding in patients with AF (11-14).”
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“Real life studies have shown that DAPT carries an out-ofhospital risk of major bleeding of up to 4–7 events per 100 person years (1, 9).”
BackgroundHaller, P. M., Sulzgruber, P., Kaufmann, C. C., Geelhoed, B., Tamargo, J. L., Waßmann, S., Schnabel, R. B., Westermann, D., Huber, K., Niessner, A., et al. (2019) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvz021 · Cited by 38 · see citing works
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Should We Still Have Bare-Metal Stents Available in Our Catheterization Laboratory?
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“In contrast, the risk of bleeding stays constant over the duration of therapy (71).”
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“A large, nationwide registry reported higher rates of bleeding with TAT compared with OAC, alone or in combination with antiplatelet monotherapy, without difference in thromboembolic risk (16).”
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“Ongoing antithrombotic treatment was determined from claimed prescriptions as previously done (11,22).”
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“However, prolonged treatment with dual or triple antiplatelet drugs can develop either poor platelet responses, which lead to antiplatelet resistance [38,39], or hyper platelet responses resulting in an increasing risk of bleeding [40].”
BackgroundPrognosis of silent atrial fibrillation after acute myocardial infarction at 1-year follow-up
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Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding
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- Authors
- Lamberts, M., Olesen, J. B., Ruwald, M. H., Hansen, C. M., Karasoy, D., Kristensen, S. L., Køber, L., Torp-Pedersen, C., Gislason, G. H., & Hansen, M. L.
- Affiliations
- Copenhagen University Hospital (DK)
- Gentofte Hospital (DK)
- ORCID
- Venue
- Circulation
- Published
- 2012-09-04
- Volume
- 126
- Issue
- 10
- Pages
- 1185-1193
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2108659563
- Cited by
- 413
- References
- 0
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 16 · 2021: 24 · 2020: 36 · 2019: 42 · 2018: 42 · 2017: 43 · 2016: 37 · 2015: 40 · 2014: 41 · 2013: 53 · 2012: 6
- FWCI
- 28.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- atrial fibrillation, bleeding risk, triple therapy, vitamin K antagonists, clopidogrel, aspirin, antiplatelet therapy, dual antiplatelet therapy, myocardial infarction, percutaneous coronary intervention, thromboembolic risk, bleeding risk assessment
- MeSH terms
- Clopidogrel, Aged, Aged, 80 and over, Aspirin, Atrial Fibrillation, Denmark, Drug Therapy, Combination, Female, Fibrinolytic Agents, Hemorrhage, Humans, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Registries, Risk Factors, Ticlopidine, Vitamin K, Cohort Studies, Comorbidity, Angioplasty, Balloon, Coronary, Stroke, Acute Coronary Syndrome
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