Drug interactions with oral anticoagulants in German nursing home residents: comparison between vitamin K antagonists and non-vitamin K antagonist oral anticoagulants based on two nested case–control studies

Jobski, Kathrin; Hoffmann, Falk; Herget–Rosenthal, Stefan; Dörks, Michael

doi:10.1007/s00392-019-01526-7

Cited by 14 publications

(28 citation statements)

References 57 publications

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“…In the present study, concomitant use of SSRIs with NOAC showed significantly increased risk of overall major bleeding events, which is consistent with recent studies on potentially interacting drugs with NOAC. 5 6 …”

Section: Discussionmentioning

confidence: 99%

“…The major bleeding events were categorized as upper GI bleeding, lower GI bleeding, intracranial bleeding, and other bleedings, including urinary tract bleeding, airway bleeding, and others, based on previous reports in the literature ( Supplementary Table 1 , only online). 4 6 14 For each case, up to 20 controls at risk of the bleeding event were randomly selected by age (±5 years), sex, episode status, and duration from diagnosis of AF to the prescription of NOACs (±1 year) using risk-set sampling. In the riskset sampling, patients could serve as controls for multiple cases, and patients were eligible to be selected as controls before becoming a case.…”

Section: Methodsmentioning

confidence: 99%

“…Comedication was assessed based on potential drug interactions with OACs reported in the literature. 6 8 17 We included NSAIDs (aceclofenac, indomethacin, sulindac, diclofenac, acemetacin, etodolac, proglumetacin, ketorolac, piroxicam, lornoxicam, meloxicam, ibuprofen, naproxen, ketoprofen, flurbiprofen, tiaprofenic acid, oxaprozin, ibuproxam, dexibuprofen, dexketoprofen, nabumetone, nimesulide, morniflumate, mefenamic acid, celecoxib, etoricoxib, and polmacoxib) and SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, and escitalopram). To examine the protective effect of PPIs on risk of upper GI bleeding, we included PPIs (omeprazole, lansoprazole, pantoprazole, dexlansoprazole, and esomeprazole) as another exposure variable.…”

Section: Methodsmentioning

confidence: 99%

“… 6 However, interactions with drugs inhibiting platelet aggregation, including non-steroidal anti-inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors (SSRIs), were not assessed 4 or showed conflicting results with previous studies. 5 6 …”

Section: Introductionmentioning

confidence: 99%

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Concomitant Use of NSAIDs or SSRIs with NOACs Requires Monitoring for Bleeding

et al. 2020

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Purpose Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an increased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF. Materials and Methods A nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined. Results The risk of bleeding events was higher in patients receiving concomitant NSAIDs [adjusted odds ratio (aOR) 1.41; 95% confidence interval (CI) 1.24–1.61] or SSRIs (aOR 1.92; 95% CI 1.52–2.42) with NOACs, compared to no use of either drug, respectively. The risk of upper gastrointestinal bleeding was higher in patients receiving concomitant NSAIDs or SSRIs without proton pump inhibitors (PPIs) (NSAIDs: aOR 2.47; 95% CI 1.26–4.83, SSRI: aOR 10.8; 95% CI 2.41–2.48) compared to no use. Conclusion When NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Concomitant Use of NSAIDs or SSRIs with NOACs Requires Monitoring for Bleeding

et al. 2020

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“…In elderly patients, NOACs may be related to less side effects due to medication interaction than VKA. For most of the above mentioned trials, the primary bleeding endpoint has been reported for elderly patients, but for major bleedings or ischemic events there is yet insufficient data reported [58]. In general, clinically significant bleedings in elderly patients were lower on NOAC/dual compared to VKA/triple strategies [15][16][17][18]49].…”

Section: Dual Strategies In Elderly Patientsmentioning

confidence: 99%

Anti-thrombotic strategies in patients with atrial fibrillation undergoing PCI

2020

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Triple anti-thrombotic therapy combining oral anticoagulation and dual anti-platelet therapy following percutaneous coronary intervention in patients with atrial fibrillation was considered as standard and recommended by guidelines. While bleeding risk is considerable with that approach, data for efficacy are scare. Several trials assessed the possibility of reducing antithrombotic treatment by mainly shortening the exposure to acetylsalicylic acid. Dropping one of the anti-platelet components might increase the risk of stent thrombosis, myocardial infarction or stroke. Despite that fear, the recent trials' primary endpoint was major and/or clinically-relevant non-major bleeding. We review data on major bleedings, intracranial bleedings and major adverse cardiovascular events from the published reports. We demonstrate that Non-Vitamin K oral anticoagulant (NOAC)-based strategies compared to VKA-based triple therapies significantly reduce the risk for TIMI-major bleedings by 39% and for intracranial bleedings by 66%, while they did not increase the risk for overall ischemic or embolic events. However, recent meta-analyses indicate an increased risk for stent thrombosis with less intense anti-thrombotic therapy. While the overall incidence rate for stent thrombosis is rather low, relative increases by about 30-60% are reported, but they did not translate into adverse clinical net-benefit ratios. This review highlights that using certain NOAC regimens proven effective for stroke prevention in AF can reduce the rate of bleeding without increasing ischemic or embolic events. Furthermore, additive ASA in triple anti-thrombotic regimens should be limited to 1 month and individual weighing of ischemic versus bleeding risk during the first 30 days seems to be reasonable.

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Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding

Rahman,

Platt,

Beradid

et al. 2024

JAMA Netw Open

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ImportanceSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized.ObjectivesTo assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk.Design, Setting, and ParticipantsA population-based, nested case-control study was conducted among patients with atrial fibrillation initiating OACs between January 2, 1998, and March 29, 2021. Patients were from approximately 2000 general practices in the UK contributing to the Clinical Practice Research Datalink. With the use of risk-set sampling, for each case of major bleeding during follow-up, up to 30 controls were selected from risk sets defined by the case and matched on age, sex, cohort entry date, and follow-up duration.ExposuresConcomitant use of SSRIs and OACs (direct OACs and vitamin K antagonists [VKAs]) compared with OAC use alone.Main Outcomes and MeasuresThe main outcome was incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding.ResultsThere were 42 190 patients with major bleeding (mean [SD] age, 74.2 [9.3] years; 59.8% men) matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). The risk peaked during the initial months of treatment (first 30 days of use: IRR, 1.74; 95% CI, 1.37-2.22) and persisted for up to 6 months. The risk did not vary with age, sex, history of bleeding, chronic kidney disease, and potency of SSRIs. An association was present both with concomitant use of SSRIs and direct OACs compared with direct OAC use alone (IRR, 1.25; 95% CI, 1.12-1.40) and concomitant use of SSRIs and VKAs compared with VKA use alone (IRR, 1.36; 95% CI, 1.25-1.47).Conclusions and RelevanceThis study suggests that among patients with atrial fibrillation, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OAC use alone, requiring close monitoring and management of risk factors for bleeding, particularly in the first few months of use.

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Drug interactions with oral anticoagulants in German nursing home residents: comparison between vitamin K antagonists and non-vitamin K antagonist oral anticoagulants based on two nested case–control studies

Cited by 14 publications

References 57 publications

Concomitant Use of NSAIDs or SSRIs with NOACs Requires Monitoring for Bleeding

Concomitant Use of NSAIDs or SSRIs with NOACs Requires Monitoring for Bleeding

Anti-thrombotic strategies in patients with atrial fibrillation undergoing PCI

Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding

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