Outcomes of Direct Oral Anticoagulants Co-Prescribed with Common Interacting Medications

Sanborn, David; Sugrue, Alan; Amin, Mustapha; Mehta, Ramila A.; Farwati, Medhat; Deshmukh, Abhishek; Sridhar, Haarini; Ahmed, Azza M.; Asirvatham, Samuel J.; Ou, Narith N.; Noseworthy, Peter A.; Killu, Ammar M.; Mulpuru, Siva K.; Madhavan, Malini

doi:10.1016/j.amjcard.2021.09.025

Cited by 5 publications

(12 citation statements)

References 24 publications

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“…Patients 80 years and older showed risk for major bleeding in the RE-LY and ARISTOTLE trials, but these results are controversial when analyzing observational studies. 23,29,31 Limitation Our data did not provide the time length of the concomitant exposure for the baseline medications studied. Whether these individuals kept on the baseline drugs of interest after the DOAC start date cannot be confirmed.…”

Section: Discussionmentioning

confidence: 99%

“…Patients 80 years and older showed risk for major bleeding in the RE-LY and ARISTOTLE trials, but these results are controversial when analyzing observational studies. 23,29,31…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown controversial results. 18,[21][22][23][24] The purpose of this study was to examine the risk of bleeding among patients taking DOACs, accounting for known risk factors that increase the risk of bleeding in a real-world setting. medication and history of previous gastrointestinal (GI) bleedings identified by ICD 9th and 10th codes were extracted from electronic health records.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown controversial results. 18,21–24 The purpose of this study was to examine the risk of bleeding among patients taking DOACs, accounting for known risk factors that increase the risk of bleeding in a real-world setting.…”

Section: Introductionmentioning

confidence: 99%

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Risk of bleeding among individuals on direct acting oral anticoagulants: an academic medical center cohort study.

Gómez-Lumbreras

Tan

Moorman-Bishir

et al. 2022

Journal of Cardiovascular Pharmacology

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Previous research has identified risk factors that may affect the risk of bleeding when individuals are exposed to oral anticoagulants. It is unclear if the risk continues to exist with the direct oral anticoagulants (DOACs). The purpose of this study was to assess the risk of bleeding in patients on DOACs (apixaban, rivaroxaban, dabigatran, edoxaban, and betrixaban) based on known risk factors including demographics, medical conditions, and concomitant medications. This study was a retrospective analysis using electronic health record data from the University of Utah Hospital (Division of Cardiovascular Medicine) of individuals receiving a DOAC from 2015 to 2020. The primary outcome of interest was bleeding events [gastrointestinal (GI) bleeding, other anatomical site bleeding (excluding GI), and any bleeding] recorded in the electronic health record that codes using International Classification of Diseases 9th and 10th codes. Known risk factors were used to predict bleeding using multivariate logistic regression. A total of 5492 patients received a DOAC during the study period. Less than half the study population were female (2287, 41.6%). During the follow-up, there were 988 patients (18.0%) experiencing a bleeding event. Of them, 351 patients (35.5%) had a GI bleeding event. Significant risk factors of GI bleeding included clopidogrel [odds ratio (OR) 1.71; 95% confidence interval (95% CI), 1.16-2.52] and previous GI bleeding episodes (OR 7.73; 95% CI,). Exposure to corticosteroids (OR 1.50; 95% CI, 1.20-1.87) and previous GI bleeding (OR 1.61; 95% CI, 1.10-2.35) were associated with an increase in bleeding at other anatomical sites (not GI included).

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Section: Discussionmentioning

confidence: 99%

“…Patients 80 years and older showed risk for major bleeding in the RE-LY and ARISTOTLE trials, but these results are controversial when analyzing observational studies. 23,29,31…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Risk of bleeding among individuals on direct acting oral anticoagulants: an academic medical center cohort study.

Gómez-Lumbreras

Tan

Moorman-Bishir

et al. 2022

Journal of Cardiovascular Pharmacology

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“…Although both the US Food and Drug Administration labels for apixaban and rivaroxaban and the American College of Cardiology, American Heart Association, American College of Clinical Pharmacy, and Heart Rhythm Society guidelines for management of atrial fibrillation acknowledge that anticoagulant management should consider drug-drug interactions, neither specifically mentions increased risk of bleeding as a potential consequence of diltiazem coadministration. Observational studies have had mixed findings, but many of these were limited by relatively small sample size, lack of an active comparator, and incomplete control for confounding.…”

Section: Introductionmentioning

confidence: 99%

Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban

Ray,

Chung,

Stein

et al. 2024

JAMA

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ImportanceDiltiazem, a commonly prescribed ventricular rate–control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation.ObjectiveTo compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol.Design, Setting, and ParticipantsThis retrospective cohort study included Medicare beneficiaries aged 65 years or older with atrial fibrillation who initiated apixaban or rivaroxaban use and also began treatment with diltiazem or metoprolol between January 1, 2012, and November 29, 2020. Patients were followed up to 365 days through November 30, 2020. Data were analyzed from August 2023 to February 2024.ExposuresDiltiazem and metoprolol.Main Outcomes and MeasuresThe primary outcome was a composite of bleeding-related hospitalization and death with recent evidence of bleeding. Secondary outcomes were ischemic stroke or systemic embolism, major ischemic or hemorrhagic events (ischemic stroke, systemic embolism, intracranial or fatal extracranial bleeding, or death with recent evidence of bleeding), and death without recent evidence of bleeding. Hazard ratios (HRs) and rate differences (RDs) were adjusted for covariate differences with overlap weighting.ResultsThe study included 204 155 US Medicare beneficiaries, of whom 53 275 received diltiazem and 150 880 received metoprolol. Study patients (mean [SD] age, 76.9 [7.0] years; 52.7% female) had 90 927 person-years (PY) of follow-up (median, 120 [IQR, 59-281] days). Patients receiving diltiazem treatment had increased risk for the primary outcome (RD, 10.6 [95% CI, 7.0-14.2] per 1000 PY; HR, 1.21 [95% CI, 1.13-1.29]) and its components of bleeding-related hospitalization (RD, 8.2 [95% CI, 5.1-11.4] per 1000 PY; HR, 1.22 [95% CI, 1.13-1.31]) and death with recent evidence of bleeding (RD, 2.4 [95% CI, 0.6-4.2] per 1000 PY; HR, 1.19 [95% CI, 1.05-1.34]) compared with patients receiving metoprolol. Risk for the primary outcome with initial diltiazem doses exceeding 120 mg/d (RD, 15.1 [95% CI, 10.2-20.1] per 1000 PY; HR, 1.29 [95% CI, 1.19-1.39]) was greater than that for lower doses (RD, 6.7 [95% CI, 2.0-11.4] per 1000 PY; HR, 1.13 [95% CI, 1.04-1.24]). For doses exceeding 120 mg/d, the risk of major ischemic or hemorrhagic events was increased (HR, 1.14 [95% CI, 1.02-1.27]). Neither dose group had significant changes in the risk for ischemic stroke or systemic embolism or death without recent evidence of bleeding. When patients receiving high- and low-dose diltiazem treatment were directly compared, the HR for the primary outcome was 1.14 (95% CI, 1.02-1.26).Conclusions and RelevanceIn Medicare patients with atrial fibrillation receiving apixaban or rivaroxaban, diltiazem was associated with greater risk of serious bleeding than metoprolol, particularly for diltiazem doses exceeding 120 mg/d.

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Pharmacokinetics and pharmacodynamics of drug‒drug interactions in hospitalized older adults treated with direct oral anticoagulants

Decaix,

Kemache,

Gay

et al. 2024

Aging Clin Exp Res

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Purpose Polypharmacy is a frequent situation in older adults that increases the risk of drug-drug interactions (DDIs), both pharmacokinetic (PK) and pharmacodynamic (PD). Direct oral anticoagulants (DOACs) are frequently prescribed in older adults, mainly because of the high prevalence of atrial fibrillation (AF). DOACs are subject to cytochrome P450 3A4 (CYP3A4)- and/or P-glycoprotein (P-gp)-mediated PK DDIs and PD DDIs when co-administered with drugs that interfere with platelet function. The aim of our study was to assess the prevalence of DDIs involving DOACs in older adults and the associated risk factors at admission and discharge. Methods This was a cross-sectional study conducted in an acute geriatric unit between January 1, 2018 and December 31, 2022, including patients over 75 years of age treated with DOACs at admission and/or discharge, for whom a comprehensive collection of co-medications was performed. Results From 909 hospitalizations collected, the prevalence of PK DDIs involving DOACs was 16.9% at admission and 20.7% at discharge, and the prevalence of PD DDIs was 20.7% at admission and 20.2% at discharge. Factors associated with DDIs were bleeding history [adjusted odds ratio (ORa) 1.74, 95% confidence interval (CI) 1.13–2.68], number of drugs > 6 (ORa 2.54, 95% CI 1.88–3.46) and reduced dose of DOACs (ORa 0.39, 95% CI 0.28–0.54) at admission and age > 87 years (ORa 0.74, 95% CI 0.55–0.99), number of drugs > 6 (ORa 2.01, 95% CI 1.48–2.72) and reduced dose of DOACs (ORa 0.41, 95% CI 0.30–0.57) at discharge. Conclusion This study provides an indication of the prevalence of DDIs as well as the profile of DDIs and patients treated with DOACs.

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Outcomes of Direct Oral Anticoagulants Co-Prescribed with Common Interacting Medications

Cited by 5 publications

References 24 publications

Risk of bleeding among individuals on direct acting oral anticoagulants: an academic medical center cohort study.

Risk of bleeding among individuals on direct acting oral anticoagulants: an academic medical center cohort study.

Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban

Pharmacokinetics and pharmacodynamics of drug‒drug interactions in hospitalized older adults treated with direct oral anticoagulants

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