Atrial Fibrillation and Stroke Risk in Patients With Cancer: A Primer for Oncologists

Cancer and atrial fibrillation (AF) are common conditions, but for patients affected with both, there is a lack of data about management of anticoagulation and cerebrovascular outcomes. In the first section of this review, we summarize the most relevant studies on stroke risk and management of AF in patients with active cancer, attempting to answer questions of whether to anticoagulate, whom to anticoagulate, and what agents to use. In the second section of the review, we suggest a decision algorithm on the basis of the available evidence and provide practical recommendations for each of the anticoagulant options. In the third section, we discuss the limitations of the available evidence. On the basis of low-quality evidence, we find that patients with cancer and AF have a risk of stroke similar to that of the general population but a substantially higher risk of bleeding regardless of the anticoagulant agent used; this makes anticoagulation-related decisions complex and evidence from the general population not immediately applicable. In general, we suggest stopping anticoagulation in patients with high risk of bleeding and in those with a moderate bleeding risk without a high thromboembolic risk and recommend anticoagulation as in the general population for patients at a low risk for bleeding. However, regardless of initial therapy, we recommend reassessing whether anticoagulation should be given at each point in the clinical course of the disease. High-quality evidence to guide anticoagulation for AF in patients with cancer is needed.

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Abstract 14763: Patients With a Perceived High-bleeding Risk in a Randomized Controlled Trial of Alert-based Computerized Decision Support for Stroke Prevention in Atrial Fibrillation: An Af-Alert Substudy

Circulation ◽

10.1161/circ.142.suppl_3.14763 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Gregory Piazza ◽

Shelley Hurwitz ◽

Brett Carroll ◽

Samuel Z Goldhaber

Keyword(s):

Atrial Fibrillation ◽

High Risk ◽

Stroke Prevention ◽

Antithrombotic Therapy ◽

Controlled Trial ◽

Bleeding Risk ◽

Computerized Decision Support ◽

Risk Of Bleeding ◽

Randomized Controlled ◽

Risk For Bleeding

Introduction: A perceived increased risk of bleeding is one of the most frequent reasons for failure to prescribe anticoagulation for stroke prevention in atrial fibrillation (AF). We previously conducted a randomized controlled trial of alert-based computerized decision support (CDS) to increase prescription of antithrombotic therapy in 458 high-risk hospitalized patients with AF who were not being anticoagulated. Hypothesis: We hypothesized that patients with a perceived high risk for bleeding would have a similar HAS-BLED score and rate of major and clinically-relevant non-major bleeding. Methods: To determine the clinical characteristics and outcomes of these patients determined to be high-risk for bleeding, we analyzed the 248 patients in the alert group. Results: A perceived high risk of bleeding was the most common reason (77%) for omitting antithrombotic therapy. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p=0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy for stroke prevention at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation over the ensuing 90 days. The frequency of major and clinically-relevant non-major bleeding was similar between the two groups. Conclusions: In conclusion, a perceived high risk of bleeding was the most common reason for failure to prescribe antithrombotic therapy after the CDS alert. History of a prior bleeding event or underlying bleeding disorder was not reflected in a higher HAS-BLED score. Implementation of an alert-based CDS with specific attention to assessment of bleeding risk and mitigation warrants further study to encourage adherence to evidence-based clinical practice guideline recommendations for stroke prevention in AF.

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Improvement of the management of anticoagulation in Atrial Fibrillation patients in the emergency and acute medical departments; a service quality improvement report

Technium BioChemMed ◽

10.47577/biochemmed.v2i3.4087 ◽

2021 ◽

Vol 2 (3) ◽

pp. 18-24

Author(s):

Amr Elkammash ◽

Yosra Taha ◽

Saleh Kanaan ◽

Martin Taylor

Keyword(s):

Atrial Fibrillation ◽

Quality Improvement ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Risk Scores ◽

Junior Doctors ◽

Improvement Project ◽

Risk Of Bleeding

Atrial fibrillation (AF) is considered one of the main causes of ischemic stroke. The CHA2DS2VASC score can predict the stroke risk. Proper anticoagulation can significantly reduce such risk. Anticoagulation involves a risk of bleeding, which can be predicted by the HAS-BLED score. The non-documentation of both AF risk scores in the medical notes of patients presenting with acute or paroxysmal AF has alerted our team, for fear of missing administering the proper anticoagulation. A baseline audit showed that the CHA2DS2VASC score was documented in 27% of such patients, while the HAS-BLED score was documented in 5% of them. A quality improvement project was planned and included two PDSA cycles over a period of five months. The first cycle was based on raising the awareness of the junior doctors on risk assessment of AF patients and the importance of anticoagulation prescription. This involved educational posters, emails, and presentations. On the second cycle, the baseline audit showed a 69% improvement (from 27% to 46%) in the rate of CHA2DS2VASC score assessment and a 140% improvement (from 5% to 12%) in the rate of HAS-BLED scoring. However, the rate of anticoagulation prescription remained almost the same in both cycles (55% and 52%). A doctors’ survey showed that they are not quite comfortable prescribing long-term anticoagulation on acute care units because of the inadequate assessment of the bleeding risk, and the associated comorbidities that can disturb the action of the oral anticoagulants. They preferred to refer the patient to a specialised AF clinic for further assessment and prescription. On auditing the patient referral on discharge, it was found that 91% of the patient were seen at the AF clinic in 2 weeks. The remainders were referred to their GP for further assessment and prescription. That seemed to be a safer way of anticoagulation prescription for such patients.

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Recurrent Stroke Risk in Pilots with Atrial Fibrillation

Aerospace Medicine and Human Performance ◽

10.3357/amhp.5326.2020 ◽

2020 ◽

Vol 91 (4) ◽

pp. 352-357

Author(s):

Jessica Tedford ◽

Valerie Skaggs ◽

Ann Norris ◽

Farhad Sahiar ◽

Charles Mathers

Keyword(s):

Atrial Fibrillation ◽

General Population ◽

Recurrent Events ◽

Stroke Risk ◽

Event Rate ◽

Recurrent Stroke ◽

Previous History ◽

Recurrent Event ◽

Recurrence Rates ◽

Medical Certification

INTRODUCTION: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in the general population and is considered disqualifying aeromedically. This study is a unique examination of significant outcomes in aviators with previous history of both AF and stroke.METHODS: Pilots examined by the FAA between 2002 and 2012 who had had AF at some point during his or her medical history were reviewed, and those with an initial stroke or transient ischemic attack (TIA) during that time period were included in this study. All records were individually reviewed to determine stroke and AF history, medical certification history, and recurrent events. Variables collected included medical and behavior history, stroke type, gender, BMI, medication use, and any cardiovascular or neurological outcomes of interest. Major recurrent events included stroke, TIA, cerebrovascular accident, death, or other major events. These factors were used to calculate CHA2DS2-VASc scores.RESULTS: Of the 141 pilots selected for the study, 17.7% experienced a recurrent event. At 6 mo, the recurrent event rate was 5.0%; at 1 yr, 5.8%; at 3 yr 6.9%; and at 5 yr the recurrent event rate was 17.3%. No statistical difference between CHA2DS2-VASc scores was found as it pertained to number of recurrent events.DISCUSSION: We found no significant factors predicting risk of recurrent event and lower recurrence rates in pilots than the general population. This suggests CHA2DS2-VASc scores are not appropriate risk stratification tools in an aviation population and more research is necessary to determine risk of recurrent events in aviators with atrial fibrillation.Tedford J, Skaggs V, Norris A, Sahiar F, Mathers C. Recurrent stroke risk in pilots with atrial fibrillation. Aerosp Med Hum Perform. 2020; 91(4):352–357.

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Abstract 77: Balancing Risks and Benefits of Anticoagulation Therapy in Atrial Fibrillation in Community Practice: Results from the ORBIT-AF Registry

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.5.suppl_1.a77 ◽

2012 ◽

Vol 5 (suppl_1) ◽

Author(s):

Michael W Cullen ◽

Sunghee Kim ◽

Jonathan P Piccini ◽

Alan S Go ◽

Gregg C Fonarow ◽

...

Keyword(s):

Atrial Fibrillation ◽

Stroke Risk ◽

Anticoagulation Therapy ◽

Bleeding Risk ◽

Community Practice ◽

Chads2 Score ◽

Risk Patients ◽

Study Population ◽

Risk Treatment ◽

The Cost

Background Oral anticoagulation (OAC) can reduce stroke risk at the cost of increased bleeding risk in those with atrial fibrillation (AF). Observational data have shown that higher-risk patients with AF most likely to benefit from OAC are less likely to receive OAC at hospital discharge. Methods We used data from ORBIT-AF Registry, a cohort of 9,589 AF patients enrolled among 173 participating outpatient practices. OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using the CHADS2 and ATRIA scores, respectively. Results The study population had a mean age of 73.5 years; 57.8% were men. Overall, 76.4% of patients received OAC. Use of OAC rose with increasing CHADS2 stroke risk, from 67% for CHADS2 <1 to 80% for CHADS2 ≥2 (p<0.0001). OAC use fell slightly with increasing ATRIA bleeding risk, from 77% for ATRIA score ≤3 to 74% with ≥5 (p=0.002 for trend). Among patients with low bleeding risk, rates of OAC increased commensurate with stroke risk (p<0.0001 for interaction; see figure). Higher bleeding risk tended to decrease rates of OAC among patients with a CHADS2 score ≥2 (p=0.13 for interaction). Conclusions In community-based outpatients with AF, use of OAC rose with increasing thromboembolic risk and declined with higher bleeding risk. These findings suggest that the risk-treatment paradox may be less that previously reported. Provision of OAC in community practice appears to appropriately consider patients' stroke and bleeding risks. Further research is required to understand how quality improvement initiatives can further improve stroke prevention.

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Abstract 18538: The ATRIA Stroke Risk Score Predicts Ischemic Stroke Better than CHADS2 and CHA2DS2-VASc in a large Swedish Cohort of Patients with Atrial Fibrillation

Circulation ◽

10.1161/circ.130.suppl_2.18538 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Sara Aspberg ◽

Yuchiao Chang ◽

Daniel Singer

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Risk Score ◽

Stroke Risk ◽

Anticoagulation Therapy ◽

Bleeding Risk ◽

Risk Scores ◽

Cut Points ◽

Net Clinical Benefit ◽

Better Than

Introduction: Atrial fibrillation (AF) is a major risk factor for acute ischemic stroke (AIS). Anticoagulation therapy (OAC) effectively prevents AIS, but increases bleeding risk. There is a need for better AIS risk prediction to optimize the anticoagulation decision in AF. The ATRIA stroke risk score (ATRIA) (table) was superior to CHADS2 and CHA2DS2-VASc in two large California community AF cohorts. We now report the performance of the 3 scores in a very large Swedish AF cohort. Methods: The cohort consisted of all Swedish patients hospitalized with a diagnosis of AF from July 1, 2005 to December 31, 2008. Predictor variables and the outcome, AIS, were obtained from inpatient ICD-10 codes. Warfarin use was determined from National Pharmacy Database. Risk scores were assessed via c-index (C) and net reclassification index (NRI). Results: The cohort included 158,370 AF patients off warfarin who contributed 340,332 person-years of follow-up, and 11,823 incident AIS, for an overall AIS rate of 3.47%/yr, higher than the 2%/yr seen in the California cohorts. Using the entire point score, ATRIA had a good C of 0.712 (0.708-0.716), significantly better than CHADS2, 0.694 (0.689-0.698), or CHA2DS2-VASc, 0.697 (0.693-0.702). Using published cut-points for Low/Moderate/High AIS risk, C deteriorated for all scores but ATRIA and CHADS2 were superior to CHA2DS2-VASc. NRI favored ATRIA; 0.16 (0.15-0.18) versus CHADS2; 0.22 (0.21-0.24) versus CHA2DS2-VASc. However, NRI decreased to near-zero when cut-points were altered to better fit the cohort’s stroke rates. Conclusion: Findings in this large Swedish AF cohort validate those in the California AF cohorts, with the ATRIA score predicting stroke risk better than CHADS2 or CHA2DS2-VASc. However, relative performance of the categorical scores varied by population stroke risk. Knowledge about this population risk may be needed to optimize cut-points on the multipoint scores to achieve better net clinical benefit from OAC.

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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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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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P675Current status of anticoagulation in patients with breast cancer and atrial fibrillation

European Heart Journal ◽

10.1093/eurheartj/ehz747.0281 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Pardo Sanz ◽

L M Rincon ◽

P Guedes Ramallo ◽

L Belarte ◽

G De Lara ◽

...

Keyword(s):

Breast Cancer ◽

Atrial Fibrillation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Bleeding Events ◽

Patients With Cancer ◽

Oncologic Patients

Abstract Aims Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. We further evaluated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with cancer. Methods The AMBER-AF registry is an observational multicentre study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain. 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. Mean follow-up was 3.1 years. Results Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. Lack of guidelines recommended therapies was more frequent among patients with cancer. Compared with patients without cancer, adjusted rates of stroke (hazard ratio [95% confidence interval]) in cancer patients were higher (1.56 [1.04–2.35]), whereas bleeding rates remained similar (1.25 [0.95–1.64]). Within the group of patients with cancer, the use of DOACs vs VKAs did not entail differences in the adjusted rates of stroke (0.91 [0.42–1.99]) or severe bleedings (1.53 [0.93–2.53]). Follow-up events Conclusions Antithrombotic management of AF frequently differs in patients with breast cancer. While breast cancer is associated with a higher risk of incident stroke, bleeding events remained similar. Patients with cancer treated with DOACs experienced similar rates of stroke and bleeding as those with VKAs.

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