Major bleeding risk associated with warfarin and co‐medications in the elderly population

Vitry, Agnès; Roughead, Elizabeth E.; Ramsay, Emmae; Preiss, Adrian K.; Ryan, Philip; Gilbert, Andrew L.; Caughey, Gillian E.; Shakib, Sepehr; Esterman, Adrian; Zhang, Ying; McDermott, Robyn

doi:10.1002/pds.2219

Cited by 48 publications

(54 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In another recent retrospective study in an elderly population (n017,600) who used warfarin, bleedingrelated hospitalization rates were significantly increased when warfarin was co-prescribed with aspirin (AdjRR 1. 44 [52]. The majority of the drugs identified through these studies are identical to those identified in our study.…”

Section: Discussionsupporting

confidence: 64%

See 1 more Smart Citation

Identification and weighting of the most critical “real-life” drug–drug interactions with acenocoumarol in a tertiary care hospital

Gschwind

Rollason

Lovis

et al. 2012

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Purpose The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution. Methods We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding.Results One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs. Conclusion Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drugs.

show abstract

Section: Discussionsupporting

confidence: 64%

“…In a recent study, the risk of bleeding was significantly increased when clopidogrel was coprescribed with warfarin [adjusted relative risk (AdjRR) 2.23, 95 % CI 1. 48-3.36] in the elderly population [52].…”

Section: Discussionmentioning

confidence: 99%

Identification and weighting of the most critical “real-life” drug–drug interactions with acenocoumarol in a tertiary care hospital

Gschwind

Rollason

Lovis

et al. 2012

Eur J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…For anticoagulants, concomitant use of clopidogrel (vs. pravastatin) with warfarin or dabigatran was associated with statistically significant 1.3‐fold and 1.2‐fold rates of serious bleeding, respectively, while the 1.3‐fold and 1.5‐fold rates for apixaban and rivaroxaban were not statistically significant. DDIs between clopidogrel and oral anticoagulants would be expected mechanistically given the independent cumulative effects of antiplatelet agents and anticoagulants on hemostasis, and the magnitude of these associations was generally consistent with prior epidemiologic studies . Concomitant use of clopidogrel (vs. pravastatin) with the NSAIDs meloxicam, piroxicam, nabumetone, and etodolac was associated with statistically significant 1.6‐fold, 2.5‐fold, 2.8‐fold, and 3.2‐fold rates (respectively) of serious bleeding, while the 1.1‐fold, 1.8‐fold, 1.9‐fold, 2.8‐fold, 2.8‐fold, and 4.4‐fold rates associated with naproxen, diclofenac, ibuprofen, oxaprozin, indomethacin, and sulindac (respectively) were not statistically significant.…”

Section: Discussionsupporting

confidence: 75%

“…DDIs between clopidogrel and oral anticoagulants would be expected mechanistically given the independent cumulative effects of antiplatelet agents and anticoagulants on hemostasis, 5,6 and the magnitude of these associations was generally consistent with prior epidemiologic studies. 2,7,8 Concomitant use of clopidogrel (vs. pravastatin) with the NSAIDs meloxicam, piroxicam, nabumetone, and etodolac was associated with statistically significant 1.6-fold, 2.5-fold, 2.8fold, and 3.2-fold rates (respectively) of serious bleeding, while the 1.1-fold, 1.8-fold, 1.9-fold, 2.8-fold, 2.8-fold, and 4.4-fold rates associated with naproxen, diclofenac, ibuprofen, oxaprozin, indomethacin, and sulindac (respectively) were not statistically significant. These findings are mechanistically plausible given independent effects of clopidogrel and NSAIDs on bleeding risk 9 and also generally consistent with prior epidemiologic studies.…”

Section: Discussionmentioning

confidence: 99%

Clopidogrel Drug Interactions and Serious Bleeding: Generating Real‐World Evidence via Automated High‐Throughput Pharmacoepidemiologic Screening

Leonard

Zhou

Brensinger

et al. 2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Few population‐based studies have examined bleeding associated with clopidogrel drug–drug interactions (DDIs). We sought to identify precipitant drugs taken concomitantly with clopidogrel (an object drug) that increased serious bleeding rates. We screened 2000–2015 Optum commercial health insurance claims to identify DDI signals. We performed self‐controlled case series studies for clopidogrel plus precipitant pairs, examining associations with gastrointestinal bleeding or intracranial hemorrhage. To distinguish native bleeding effects of a precipitant, we reexamined associations using pravastatin as a negative control object drug. Among 431 analyses, 28 clopidogrel plus precipitant pairs were statistically significantly positively associated with serious bleeding. Ratios of rate ratios ranged from 1.13–3.94. Among these pairs, 13 were expected given precipitant drugs alone increased and/or were harbingers of serious bleeding. The remaining 15 pairs constituted new DDI signals, none of which are currently listed in two major DDI knowledge bases.

show abstract

“…(2) Following the approach by Vitry et al . , follow‐up days with exposure to other potentially interacting medications, including non‐steroidal anti‐inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors (SSRI), or clopidogrel, were excluded from the main analysis. In addition, days on NSAIDs and SSRIs were excluded from the first sensitivity analysis.…”

Section: Methodsmentioning

confidence: 99%

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Korhonen

Tiittanen

Kastarinen

et al. 2018

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

show abstract

Major bleeding risk associated with warfarin and co‐medications in the elderly population

Abstract: Models assessing bleeding risk with warfarin should take account of the range of potentially harmful medicine combinations used in elderly people with comorbid conditions.

Cited by 48 publications

References 42 publications

Identification and weighting of the most critical “real-life” drug–drug interactions with acenocoumarol in a tertiary care hospital

Identification and weighting of the most critical “real-life” drug–drug interactions with acenocoumarol in a tertiary care hospital

Clopidogrel Drug Interactions and Serious Bleeding: Generating Real‐World Evidence via Automated High‐Throughput Pharmacoepidemiologic Screening

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Contact Info

Product

Resources

About