Association of Type of Antidepressant Initiation with Bleeding Risk in Atrial Fibrillation Patients Taking Oral Anticoagulants

Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This has prompted a search for new anticoagulants that could overcome many of the inconveniences of dose variability and anticoagulant monitoring associated with warfarin, but without sacrificing efficacy in thromboprophylaxis. The arrival of new oral anticoagulants has been complemented by improved risk stratification schemes, which permit clinicians to easily and reliably identify patients requiring anticoagulation and their bleeding risk. These advances in AF treatment will hopefully translate into improved outcomes for patients, especially as our experience with the new agents grows.

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Bleeding risk of antiplatelet drugs compared with oral anticoagulants in older patients with atrial fibrillation: a systematic review and meta‐analysis

Journal of Thrombosis and Haemostasis ◽

10.1111/jth.13697 ◽

2017 ◽

Vol 15 (7) ◽

pp. 1500-1510 ◽

Cited By ~ 11

Author(s):

M. Melkonian ◽

W. Jarzebowski ◽

E. Pautas ◽

V. Siguret ◽

J. Belmin ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Older Patients ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Antiplatelet Drugs

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Abstract 14808: Bleed Outcomes Following Coronary Artery Stent: Risk Associated With Combined Antithrombotic Therapy Common in Atrial Fibrillation: Insights From Medicare Claims Data

Circulation ◽

10.1161/circ.132.suppl_3.14808 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Gregory A Dadekian ◽

Jeremy Smith ◽

Aaron V Kaplan ◽

Nancy E Morden

Keyword(s):

Atrial Fibrillation ◽

Coronary Artery ◽

Cox Regression ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

National Sample ◽

Individual Characteristics ◽

Coronary Artery Stent ◽

Estimated Risk ◽

Medicare Claims Data

Background: Platelet inhibitor (PI) use following coronary artery stent confers bleed risks, especially for atrial fibrillation (AF) patients on oral anticoagulants (OAC), a subgroup often excluded from randomized stent trials. We studied a national sample of elderly stent recipients to quantify bleed risks associated with combined OAC and PI, pharmacotherapy common in AF. Methods: Using a 40% Medicare random sample denominator file and associated inpatient, outpatient (2003-2012) and prescription (2006-2012) claims, we studied patients age 65 and older receiving a coronary artery stent. We measured OAC and/or prescription PI use after stent placement. Cox regression models estimated risk of bleed events adjusting for individual characteristics, morbidities, and time-varying medication use. Results Overall, 165,718 patients in our sample received a stent, 2006-2012; 20.4% had AF; mean age was 73.8 (SD 6.3). In the first month post-stent, among AF patients, 40.7% received OAC, 85.6% prescription PI, 35.9% both; among non-AF patients corresponding use was 3.5%, 90.3% and 3.1% respectively. At 13 months post stent, 61.0% of AF patients and 71.1% of non-AF patients continued using prescription PIs while 15.5% and 1.7% respectively remained on both PI and OAC therapy. Compared to those taking only prescription PIs, the risk of bleeding associated with warfarin plus PI was 2.05 (95% CI: 1.97 - 2.13); the risk associated with novel OACs (dabigatran or rivaroxaban) plus PIs was 2.60 (95% CI: 2.26 - 2.99). Conclusions: In a national, older population combined OAC and PI use following stent is common in AF patients and associated with bleeding risk. These findings should inform stent selection and antithrombotic strategies. The association between novel OACs and bleeding was unexpected and warrants further exploration as these products gain use.

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Abstract 140: Comparison of Major Complication of Oral Anticoagulants in Non-Valvular Atrial Fibrillation: Systematic Review and Meta-Analyses

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.140 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Hong Seok Lee

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Gi Bleeding ◽

Ischemic Stroke Risk ◽

Meta Analyses

Background: Oral anticoagulants known as a novel oral anticoagulant have been used for the management of non -valvular atrial fibrillation. There was no enough study regarding the efficacy and safety of three major new oral anticoagulants. We assessed major three oral anticoagulants in terms of major bleeding complication and stroke prevention by meta-analyses studies comparing those drugs. Method: Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2016). RevMan and ITC software were used for direct comparisons, respectively. Results: Apixaban (N=6020), versus dabigatran(N=12038), apixaban versus rivaroxaban(N=8503) and rivaroxaban versus dabigatran were analyzed directly. There was significantly higher major bleeding risks in apixaban compared to dabigatran (both 110mg and 150mg) after adjusting baseline bleeding risk (Relative risk 3.41, 95% confidence interval(2.61 to 4.47) in 110mg, (5.62, 4.83 to 6.54) in 150mg. Intracranial bleeding risk in apixaban was significantly higher than in dabigatran (10.5, 6.10 to18.01). However, apixaban had less GI bleeding risk compared to dabigatran (0.80 , 0.65 to 0.98) and also had less ischemic stroke risk (0.31,0.22 to 0.42). Rivaroxaban showed higher major bleeding risk than dabigatran 110mg (2.34 , 1.81 to 3.03), however, Rivaroxaban had less bleeding risk compared to dabigatran 150mg (0.41, 0.35 to 0.46). Dabigatran 110mg and 150mg had less GI bleeding risk compared to rivaroxaban (0.31 , 0.24 to 0.39) and (0.23,0.17 to 0.29) respectively. Ischemic stroke risk was also decreased in dabigatran110mg (0.46, 0.38 to 0.57). and 150mg (0.66 ,0.52 to 0.83). Conclusion: Observed oral anticoagulants were associated with various complications. Overall, apixaban had higher intracranial bleeding risk than dabigatran. The highest GI bleeding risk in rivaroxaban compared to apixaban and dabigatran. Ischemic stroke risk was the highest in dabigatran. In conclusion, we may use those oral anticoagulant based on risks rates, however, a larger study with longer follow-up is needed to corroborate findings.

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Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients

Circulation ◽

10.1161/circ.142.suppl_3.15396 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Alexander C Perino ◽

Krishna Pundi ◽

Jun Fan ◽

Susan K Schmitt ◽

Mitra Kothari ◽

...

Keyword(s):

Atrial Fibrillation ◽

Warfarin Therapy ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Risk Of Bleeding ◽

Warfarin Treatment ◽

Treatment Analysis ◽

Using Data ◽

Favorable Safety

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.

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GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study

BMJ Open ◽

10.1136/bmjopen-2019-033283 ◽

2019 ◽

Vol 9 (11) ◽

pp. e033283 ◽

Cited By ~ 3

Author(s):

Frederik Dalgaard ◽

Karen Pieper ◽

Freek Verheugt ◽

A John Camm ◽

Keith AA Fox ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Major Bleeding ◽

Risk Model ◽

Oral Anticoagulants ◽

External Validation ◽

Bleeding Risk ◽

Risk Scores ◽

Secondary Outcome

ObjectivesTo externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort.DesignRetrospective cohort study.SettingDanish nationwide registries.Participants90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year.Primary and secondary outcome measuresExternal validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes.ResultsOf the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66–83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60).ConclusionIn a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding.

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BLEEDING RISK OF DIRECT ORAL ANTICOAGULANTS COMPARED WITH WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION AND HEART FAILURE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(17)34289-4 ◽

2017 ◽

Vol 69 (11) ◽

pp. 900 ◽

Cited By ~ 1

Author(s):

Lingyun Lu ◽

Alberta Warner ◽

Zunera Ghaznavi ◽

Donald Chang ◽

Nikolas Tubert ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk

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Combination of Oral Anticoagulants and Single Antiplatelets versus Triple Therapy in Nonvalvular Atrial Fibrillation and Acute Coronary Syndrome: Stroke Prevention among Asians

International Journal of Angiology ◽

10.1055/s-0040-1708477 ◽

2020 ◽

Vol 29 (02) ◽

pp. 088-097

Author(s):

Anwar Santoso ◽

Sunu B. Raharjo

Keyword(s):

Atrial Fibrillation ◽

Acute Coronary Syndrome ◽

Triple Therapy ◽

Stroke Prevention ◽

Thrombus Formation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Nonvalvular Atrial Fibrillation ◽

Coronary Syndrome

AbstractAtrial fibrillation (AF), the most prevalent arrhythmic disease, tends to foster thrombus formation due to hemodynamic disturbances, leading to severe disabling and even fatal thromboembolic diseases. Meanwhile, patients with AF may also present with acute coronary syndrome (ACS) and coronary artery disease (CAD) requiring stenting, which creates a clinical dilemma considering that majority of such patients will likely receive oral anticoagulants (OACs) for stroke prevention and require additional double antiplatelet treatment (DAPT) to reduce recurrent cardiac events and in-stent thrombosis. In such cases, the gentle balance between bleeding risk and atherothromboembolic events needs to be carefully considered. Studies have shown that congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, and previous stroke or transient ischemic attack (TIA; doubled)–vascular disease, age 65 to 74 years, sex category (female; CHA2DS2-VASc) scores outperform other scoring systems in Asian populations and that the hypertension, abnormal renal/liver function (1 point each), stroke, bleeding history or predisposition, labile international normalized ratio (INR), elderly (>65 years), drugs/alcohol concomitantly (1 point each; HAS-BLED) score, a simple clinical score that predicts bleeding risk in patients with AF, particularly among Asians, performs better than other bleeding scores. A high HAS-BLED score should not be used to rule out OAC treatment but should instead prompt clinicians to address correctable risk factors. Therefore, the current review attempted to analyze available data from patients with nonvalvular AF who underwent stenting for ACS or CAD and elaborate on the direct-acting oral anticoagulant (DOAC) and antiplatelet management among such patients. For majority of the patients, “triple therapy” comprising OAC, aspirin, and clopidogrel should be considered for 1 to 6 months following ACS. However, the optimal duration for “triple therapy” would depend on the patient's ischemic and bleeding risks, with DOACs being obviously safer than vitamin-K antagonists.

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Role of Biological Markers for Cerebral Bleeding Risk STRATification in Patients with Atrial Fibrillation on Oral Anticoagulants for Primary or Secondary Prevention of Ischemic Stroke (Strat-AF Study): Study Design and Methodology

Medicina ◽

10.3390/medicina55100626 ◽

2019 ◽

Vol 55 (10) ◽

pp. 626 ◽

Cited By ~ 3

Author(s):

Anna Poggesi ◽

Carmen Barbato ◽

Francesco Galmozzi ◽

Eleonora Camilleri ◽

Francesca Cesari ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Biological Markers ◽

Oral Anticoagulant ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Circulating Biomarkers ◽

Cerebral Mri

Background and Objectives: In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. Cerebral small vessel disease (SVD) represents the pathologic substrate for primary intracerebral hemorrhage and ischemic stroke. We hypothesize that biological markers—both circulating and imaging-based—and their possible interaction, might improve the prediction of bleeding risk in AF patients under treatment with any type of oral anticoagulant. Materials and Methods: The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with AF, aged 65 years or older, and with no contraindications to magnetic resonance imaging (MRI), referring to Center of Thrombosis outpatient clinic of our University Hospital for the management of oral anticoagulation therapy. Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral MRI, and circulating biomarkers assessment at baseline and after 18 months. The main outcome is SVD progression—particularly microbleeds—as a selective surrogate marker of hemorrhagic complication. Stroke occurrence (ischemic or hemorrhagic) and the progression of functional, cognitive, and motor status will be evaluated as secondary outcomes. Circulating biomarkers may further improve predictive potentials. Results: Starting from September 2017, 194 patients (mean age 78.1 ± 6.7, range 65–97; 61% males) were enrolled. The type of AF was paroxysmal in 93 patients (48%), and persistent or permanent in the remaining patients. Concerning the type of oral anticoagulant, 57 patients (29%) were on vitamin K antagonists, and 137 (71%) were on direct oral anticoagulants. Follow-up clinical evaluation and brain MRI are ongoing. Conclusions: The Strat-AF study may be an essential step towards the exploration of the role of a combined clinical biomarker or multiple biomarker models in predicting stroke risk in AF, and might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting stroke risk and improvement in clinical outcomes in a cost-effective fashion.

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