The nature and frequency of potential warfarin drug interactions that increase the risk of bleeding in patients with atrial fibrillation

Howard, Patricia A.; Ellerbeck, Edward F.; Engelman, Kimberly K.; Patterson, Kelly L.

doi:10.1002/pds.748

Cited by 45 publications

(38 citation statements)

References 51 publications

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“…However, the type of most frequently prescribed concurrent medicines varies between studies and countries, probably because of different therapeutic traditions and selection of medicines [18,19,29]. The use of potentially interacting medicines among anticoagulant users varies substantially between studies (up to 80% is seen in prescription database studies and around 50% in clinical case control studies) [10,18,19,29].…”

Section: Discussionmentioning

confidence: 99%

Warfarin‐associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system

Narum

Solhaug

Myhr

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Bleeding is the main adverse drug reaction of warfarin use. • Several medicines, herbal products and dietary supplements may interact with warfarin. • A high percentage of patients on warfarin receive potentially interacting substances. WHAT THIS STUDY ADDS • Potentially interacting medicines were used in more than 50% of the warfarin‐associated bleeding events reported to the Norwegian spontaneous reporting system. • Only a minority of the concomitant medicines were reported as suspected or interacting in the reporters' assessments. • There was a higher degree of under‐reporting of pharmacokinetically than of pharmacodynamically interacting medicines. AIMS To study warfarin associated bleeding events reported to the Norwegian spontaneous reporting system and evaluate the differences in assessment of potentially interacting medicines between reporters and evaluators. METHODS Data on bleeding events on warfarin were retrieved from the Norwegian spontaneous reporting system database. Key measurements were time to bleeding, use of concomitant medications and the evaluation done by reporters. RESULTS In 289 case reports a total of 1261 medicines (median 4.0 per patient, range 1–17) was used. The evaluators (authors of this article) identified 546 medicines including warfarin (median 2.0 per patient, range 1–7) that could possibly cause bleeding alone or in combination. Reporters assessed 349 medicines (median 1.0 per patient, range 1–4) as suspect. Evaluators identified 156 pharmacokinetic and 101 pharmacodynamic interactions, compared with 19 pharmacokinetic and 56 pharmacodynamic interactions reported as suspected by the reporters. Time to bleeding was stated in 224 reports. Among the early bleeding events, the reports on warfarin without interacting medicines showed the highest INR (international normalized ratio). Heparin was used in 17/21 reported bleeding events during the first week on warfarin. Among the late bleeding events, reports with pharmacokinetic interacting medicines had the highest INR. CONCLUSIONS Concomitant use of potentially interacting medicines was involved in the majority of the warfarin‐associated bleeding events reported to the Norwegian spontaneous reporting system. Reporters assessed mostly warfarin as the only contributor to bleeding. In particular, pharmacokinetically interacting medicines were not suspected as contributing to bleeding.

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Section: Discussionmentioning

confidence: 99%

Warfarin‐associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system

Narum

Solhaug

Myhr

et al. 2011

Brit J Clinical Pharma

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“…In many countries, warfarin is the coumarin of first choice. Potential drug interactions during anticoagulant therapy with warfarin have been shown to be a frequent issue, as well [8,9]. Among 134,833 patients receiving long-term warfarin therapy, 109,998 (81.6%) were prescribed a concurrent prescription for at least one PID [8].…”

Section: Discussionmentioning

confidence: 99%

Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands

2007

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Objective Coumarin anticoagulants are prone to potentially life-threatening drug-drug interactions due to a combination of unfavorable properties. However, real life data on the actual occurrence are scarce. The aim of this study was to quantify and qualify potential drug interactions with coumarin anticoagulants in daily practice. Methods A cohort study including all users of phenprocoumon or acenocoumarol during the period 1991-2003 in the PHARMO Record Linkage System. All 24 individual drugs and 11 drug groups interacting with coumarins according to central database used in the Dutch pharmacies were considered. Main outcome measure Frequency and type of potential drug interactions during anticoagulant therapy with coumarins. Results 48,627 out of 76,455 mainly acenocoumarol-users (64%) were dispensed at least one potentially interacting drug (PID) during anticoagulant therapy. About 35% of these cases were dispensed a (very) strongly interacting drug, whereas 3% were dispensed a contraindicated drug. Antibacterial drugs and NSAIDs (39% and 37% of all users, respectively) were the most frequently dispensed PIDs. Conclusion Potential drug interactions with coumarins frequently occur in daily practice, confronting two-thirds of patients with an increased risk of bleeding. To a large part, this is attributable to commonly prescribed medication like antibacterial drugs and NSAIDs. This situation substantiates the need for proper monitoring or new anticoagulants with less drug-drug interactions.

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“…These drugs were grouped as antibiotics, nonsteroidal antiinflammatory drugs, and other medications, including amiodarone, omeprazole, sertraline, phenytoin, heparin, and cisapride. 6 …”

Section: Study Variablesmentioning

confidence: 99%

“…[3][4][5] In a previous study, we found that Ϸ20% of AF patients receive combined warfarin-antiplatelet therapy. 6 The goals of the current study in elderly AF patients are to examine the influence of patient-specific factors on concomitant warfarin-antiplatelet therapy and the potential impact of combined therapy on major bleeding risk.…”

mentioning

confidence: 99%

Combined Anticoagulant–Antiplatelet Use and Major Bleeding Events in Elderly Atrial Fibrillation Patients

Shireman

Howard

Kresowik

et al. 2004

Stroke

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206

142

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Background and Purpose-Bleeding risks from combined antiplatelet-warfarin therapy have not been well-described in clinical practice. We examined antiplatelet therapy among warfarin users and the impact on major bleeding rates. Methods-Retrospective cohort analysis of persons discharged on warfarin after an atrial fibrillation admission using data from Medicare's National Stroke Project. Data included Medicare claims, enrollment information, and medical record abstracted data. Logistic regression and Cox proportional hazards models were used to predict concurrent antiplatelet use and hospitalization with a major acute bleed within 90 days after discharge from the index AF admission. Results-10 093 warfarin patients met inclusion criteria with a mean age of 77 years; 19.4% received antiplatelet therapy.Antiplatelet use was less common among women, older persons, and persons with cancer, terminal diagnoses, dementia, and bleeding history. Persons with coronary disease were more likely to receive an antiplatelet agent. Antiplatelets increased major bleeding rates from 1.3% to 1.9% (Pϭ0.052). In the multivariate analysis, factors associated with bleeding events included age (OR, 1.03; 95% CI, 1.002 to 1.05), anemia (OR, 2.52; 95% CI, 1.64 to 3.88), a history of bleeding (OR, 2.40; 95% CI, 1.71 to 3.38), and concurrent antiplatelet therapy (OR, 1.53; 95% CI, 1.05 to 2.22). Conclusions-Although concerns about increased bleeding risk with combined warfarin-antiplatelet therapy are not unfounded, the risk of bleeding is moderately increased. The decision to use concurrent antiplatelet therapy appears to be tempered by cardiac and bleeding risk factors.

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The nature and frequency of potential warfarin drug interactions that increase the risk of bleeding in patients with atrial fibrillation

Abstract: AF patients discharged on warfarin were frequently prescribed concomitant medications that increase bleeding risks. These patients should be closely monitored and counseled to watch for signs of bleeding.

Cited by 45 publications

References 51 publications

Warfarin‐associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system

Warfarin‐associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system

Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands

Combined Anticoagulant–Antiplatelet Use and Major Bleeding Events in Elderly Atrial Fibrillation Patients

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