Cancer-associated venous thrombosis in adults (second edition): A British Society for Haematology Guideline.

A shared decision on the most appropriate agent for the treatment of cancer-associated thrombosis should consider the following factors, which should be reassessed as patients continue along their cancer care pathway: risk of bleeding; tumour site; suitability of oral medications; potential for drug-drug interactions; and patient preference and values regarding choice of drug. Continuing anticoagulation beyond 6 months in patients with cancer-associated venous thromboembolism and active cancer is recommended.

Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer.

BACKGROUND: In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. METHODS: The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. RESULTS: In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. CONCLUSION: The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.

Can we collect health-related quality of life information from anticoagulated atrial fibrillation participants who have recently experienced a bleed? An observational feasibility study in primary and secondary care in Wales and through a UK online forum.

OBJECTIVE: To evaluate the feasibility of recruiting participants diagnosed with atrial fibrillation (AF) taking oral anticoagulation therapies (OATs) and recently experiencing a bleed to collect health-related quality of life (HRQoL) information. DESIGN: Observational feasibility study. The study aimed to determine the feasibility of recruiting participants with minor and major bleeds, the most appropriate route for recruitment and the appropriateness of the patient-reported outcome measures (PROMs) selected for collecting HRQoL information in AF patients, and the preferred format of the surveys. SETTING: Primary care, secondary care and via an online patient forum. PARTICIPANTS: The study population was adult patients (≥18) with AF taking OATs who had experienced a recent major or minor bleed within the last 4 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes - PROMs: EuroQol 5 Dimensions-5 Levels, Perception of Anticoagulant Treatment Questionnaire, part 2 only (part 2), atrial fibrillation effect on quality of life. Secondary outcomes - Location of bleed, bleed severity, current treatment, patient perceptions of HRQoL in relation to bleeding events. RESULTS: We received initial expressions of interest from 103 participants. We subsequently recruited 32 participants to the study-14 from primary care and 18 through the AF forum. No participants were recruited through secondary care. Despite 32 participants consenting, only 26 initial surveys were completed. We received follow-up surveys from 11 participants (8 primary care and 3 AF forum). COVID-19 had a major impact on the study. CONCLUSIONS: Primary care was the most successful route for recruitment. Most participants recruited to the study experienced a minor bleed. Further ways to recruit in secondary care should be explored, especially to capture more serious bleeds. TRIAL REGISTRATION NUMBER: The study is registered in the Clinicaltrials.gov database, NCT04921176.

HIDDEN2: Study protocol for the hospital deep vein thrombosis detection study in patients with cancer receiving palliative care.

INTRODUCTION: Medical patients, admitted acutely to hospital, are at risk of venous thromboembolism (VTE). Clinical guidelines advise thromboprophylaxis prophylaxis for those at high risk of VTE. VTE is a common sequela of cancer, but guidelines take little consideration of cancer as an independent risk factor and their utility in palliative care patients is unclear. The hospice inpatient deep vein thrombosis (DVT) detection study (HIDDen) reported a 28% prevalence of asymptomatic iliofemoral DVT in hospice patients of poor performance status (PS) and prognosis, calling into question the utility of thromboprophylaxis in the palliative care setting. However, the majority of cancer inpatients receiving palliative care are admitted to hospital through the acute medical setting, yet their risk factors for VTE may differ from those admitted to hospices. OBJECTIVE: To better understand the prevalence and behaviours of VTE in patients with cancer receiving palliative care who are admitted as an acute medical emergency. DESIGN: Multicentre, observational cohort study. SETTING: Secondary care acute hospitals in South Wales, UK. PATIENTS: We plan to recruit 232 patients≥18 years old with a diagnosis of incurable cancer, and/or receiving palliative or best supportive care who are admitted acutely to hospital. Patients will be followed up for a maximum of 6 months following registration. PRIMARY OUTCOME: Presence of lower extremity DVT. SECONDARY OUTCOMES: Symptom burden attributed to DVT or pulmonary embolism, patient PS, patient demographics and development of new VTE within 90 days of registration. ANALYSIS: The study statistical analysis plan will document analysis, methodology and procedures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee, reference 22/WA/0037 (IRAS 306352)-the main trial results will be analysed as soon as practically possible and the publication shared with investigators and on sponsor website; applications to access trial data will be subject to sponsor review process.

SAIL study of stroke, systemic embolism and bleeding outcomes with warfarin anticoagulation in non-valvular atrial fibrillation (S4-BOW-AF).

Aims: In patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin, the association between guideline defined international normalised ratio (INR) control and adverse outcomes in unknown. We aimed to (i) determine stroke and systemic embolism (SSE) and bleeding events in NVAF patients prescribed warfarin; and (ii) estimate the increased risk of these adverse events associated with poor INR control in this population. Methods and results: Individual-level population-scale linked patient data were used to investigate the association between INR control and both SSE and bleeding events using (i) the National Institute for Health and Care Excellence (NICE) criteria of poor INR control [time in therapeutic range (TTR) <65%, two INRs <1.5 or two INRs >5 in a 6-month period or any INR >8]. A total of 35 891 patients were included for SSE and 35 035 for bleeding outcome analyses. Mean CHA2DS2-VASc score was 3.5 (SD = 1.7), and the mean follow up was 4.3 years for both analyses. Mean TTR was 71.9%, with 34% of time spent in poor INR control according to NICE criteria.SSE and bleeding event rates (per 100 patient years) were 1.01 (95%CI 0.95-1.08) and 3.4 (95%CI 3.3-3.5), respectively, during adequate INR control, rising to 1.82 (95%CI 1.70-1.94) and 4.8 (95% CI 4.6-5.0) during poor INR control.Poor INR control was independently associated with increased risk of both SSE [HR = 1.69 (95%CI = 1.54-1.86), P < 0.001] and bleeding [HR = 1.40 (95%CI 1.33-1.48), P < 0.001] in Cox-multivariable models. Conclusion: Guideline-defined poor INR control is associated with significantly higher SSE and bleeding event rates, independent of recognised risk factors for stroke or bleeding.

A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK.

OBJECTIVE: Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking. This review presents consensus expert opinion alongside evaluation of evidence to support healthcare professionals in the use of direct factor Xa inhibitors in cancer-associated VTE. METHODS: Recent guidelines, meta-analyses, reviews and clinical studies on anticoagulation therapy for cancer-associated VTE were used to direct clinically relevant topics and evidence to be systematically discussed using nominal group technique. The consensus manuscript and recommendations were developed based on these discussions. RESULTS: Considerations when prescribing anticoagulant therapy for cancer-associated VTE include cancer site and stage, systemic anti-cancer therapy (including vascular access), drug-drug interactions, length of anticoagulation, quality of life and needs during palliative care. Treatment of patients with kidney or liver impairment, gastrointestinal disorders, extremes of bodyweight, elevated bleeding or recurrence risk, VTE recurrence and COVID-19 is discussed. CONCLUSION: Anticoagulant therapy for cancer-associated VTE patients should be carefully selected with consideration given to the relative benefits of specific drugs when individualizing care. Direct factor Xa inhibitors are typically the treatment of choice for preventing VTE recurrence in non-cancer patients and should also be considered as such for cancer-associated VTE in most situations.

Investigating the feasibility of recruitment to an observational, quality-of-life study of patients diagnosed with atrial fibrillation (AF) who have experienced a bleed while anticoagulated: EQUAL-AF feasibility study protocol.

BACKGROUND: Oral anticoagulation therapies (OATs) are often prescribed in conjunction with medications to restore normal heart rate rhythm which can limit the risk of an atrial fibrillation (AF) related stroke and systemic thromboembolism. However, they are associated with the serious side effect of bleeding. Both clinically relevant nonmajor bleeding (CRNMB) and major bleeding while anticoagulated are believed to have a significant impact on patient quality of life (QoL). There is currently limited research into the effect bleeding has on QoL. The aim of this study is to evaluate the feasibility of identifying and recruiting patients diagnosed with AF, who are taking OATs and have recently experienced a bleed and collecting information on their QoL. METHODS: We will recruit a minimum of 50 patients to this cross-sectional, observational study. We will recruit from general practices, secondary care, and through an online AF forum. We will ask participants to complete three validated patient-reported outcome measures (PROMs), EQ5D, AFEQT, and PACT-Q, approximately 4 weeks following a bleed and again 3 months later. We will randomly select a subset of 10 participants (of those who agree to be interviewed) to undergo a structured interview with a member of the research team to explore the impact of bleeding on their QoL and to gain feedback on the three PROMs used. We will undertake a descriptive analysis of the PROMs and demographic data. We will analyse the qualitative interviews thematically to identify key themes. DISCUSSION: We aim to establish if it is possible to recruit patients and use PROMs to collect information regarding how patient QoL is affected when they experience either a clinically relevant non-major bleed (CRNMB) or major bleed while taking OATs for the management of AF. We will also explore the appropriateness, or otherwise, of the three identified PROMs for assessing quality of life following a bleed. PROMS: Three PROMs were selected following a literature review of similar QoL studies and using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for comparison. A review of the current literature produced no suitable validated PROM to record QoL experiences in patients who have been diagnosed with AF and have experienced a bleed while anticoagulated. As such, the EQ5D, AFEQT, and PACT-Q (part 2) were deemed most appropriate for use in this feasibility study. TRIAL REGISTRATION: The trial has been adopted onto the NIHR Portfolio (ID no. 47771) and registered with www. CLINICALTRIALS: gov (no. NCT04921176) retrospectively registered in June 2021.

Illustrated State-of-the-Art Capsules of the ISTH 2022 Congress.

The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion. This ensures no one misses out. The 2022 scientific program highlights new developments in hemophilia and its treatment, acquired and other inherited bleeding disorders, thromboinflammation, platelets and coagulation, clot structure and composition, fibrinolysis, vascular biology, venous thromboembolism, women's health, arterial thrombosis, pediatrics, COVID-related thrombosis, vaccine-induced thrombocytopenia with thrombosis, and omics and diagnostics. These areas are elegantly reviewed in this Illustrated Review article. The Illustrated Review is a highlight of the ISTH Congress. The format lends itself very well to explaining the science, and the collection of beautiful graphical summaries of recent developments in the field are stunning and self-explanatory. This clever and effective way to communicate research is revolutionary and different from traditional formats. We hope you enjoy this article and will be inspired by its content to generate new research ideas.

Thirty-day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life-threatening direct oral anticoagulant-related bleeding.

Objective: Compare 30-day mortality among patients receiving the specific reversal agent andexanet alfa versus replacement prothrombin complex concentrate (PCC) in the management of direct-acting oral anticoagulant (DOAC)-related bleeds. Methods: Two patient-level datasets were used: ANNEXA-4, a prospective, single-arm trial of patients taking apixaban or rivaroxaban who received andexanet alfa and ORANGE, a prospective, observational study of anticoagulated patients in UK hospitals, some of whom received PCC. Patients were propensity score matched based on demographic and clinical characteristics. Subgroup analyses were performed by bleed type (intracranial hemorrhage [ICH], gastrointestinal [GI], other). Relative risk (RR) of all-cause 30-day mortality was calculated. Results: 322 ANNEXA-4 patients treated with andexanet alfa (mean age = 77.7 years; 64.9% ICH) were matched with 88 ORANGE patients treated with PCC (mean age = 74.9 years, 67.1% ICH). Adjusted 30-day mortality for patients treated with andexanet alfa (14.6%) was lower than patients treated with PCC (34.1%; RR, 0.43; 95% CI, 0.29-0.63). In the ICH subgroup, patients treated with andexanet alfa had lower mortality (15.3%) than patients treated with PCC (48.9%; RR, 0.31; 95% CI, 0.20-0.48). Mortality risk was lowest for patients in the GI subgroup but did not differ significantly by treatment (12.2% for andexanet alfa vs 25.0% for PCC; RR, 0.49; 95% CI, 0.21-1.16). Conclusions: In this propensity score-matched comparison across 2 independent datasets, adjusted 30-day mortality rates were lower for patients treated with andexanet alfa than in matched patients receiving PCC. This indirect comparison was limited in that it could not account for several highly predictive variables including GCS score, hematoma volume, and expected survival. Further research is warranted to confirm the mortality differences between reversal/replacement agents for DOAC-related bleeding.

Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study.

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.

Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update.

This is a collaboration between the British Society of Gastroenterology (BSG) and the European Society of Gastrointestinal Endoscopy (ESGE), and is a scheduled update of their 2016 guideline on endoscopy in patients on antiplatelet or anticoagulant therapy. The guideline development committee included representatives from the British Society of Haematology, the British Cardiovascular Intervention Society, and two patient representatives from the charities Anticoagulation UK and Thrombosis UK, as well as gastroenterologists. The process conformed to AGREE II principles and the quality of evidence and strength of recommendations were derived using GRADE methodology. Prior to submission for publication, consultation was made with all member societies of ESGE, including BSG. Evidence-based revisions have been made to the risk categories for endoscopic procedures, and to the categories for risks of thrombosis. In particular a more detailed risk analysis for atrial fibrillation has been employed, and the recommendations for direct oral anticoagulants have been strengthened in light of trial data published since the previous version. A section has been added on the management of patients presenting with acute GI haemorrhage. Important patient considerations are highlighted. Recommendations are based on the risk balance between thrombosis and haemorrhage in given situations.

Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update.

This is a collaboration between the British Society of Gastroenterology (BSG) and the European Society of Gastrointestinal Endoscopy (ESGE), and is a scheduled update of their 2016 guideline on endoscopy in patients on antiplatelet or anticoagulant therapy. The guideline development committee included representatives from the British Society of Haematology, the British Cardiovascular Intervention Society, and two patient representatives from the charities Anticoagulation UK and Thrombosis UK, as well as gastroenterologists. The process conformed to AGREE II principles, and the quality of evidence and strength of recommendations were derived using GRADE methodology. Prior to submission for publication, consultation was made with all member societies of ESGE, including BSG. Evidence-based revisions have been made to the risk categories for endoscopic procedures, and to the categories for risks of thrombosis. In particular a more detailed risk analysis for atrial fibrillation has been employed, and the recommendations for direct oral anticoagulants have been strengthened in light of trial data published since the previous version. A section has been added on the management of patients presenting with acute GI haemorrhage. Important patient considerations are highlighted. Recommendations are based on the risk balance between thrombosis and haemorrhage in given situations.

CHA2DS2-VASc and HAS-BLED risk scores and real-world oral anticoagulant prescribing decisions in atrial fibrillation.

Background: Guidelines indicate that oral anticoagulant (OAC) treatment decisions in atrial fibrillation should be based on a balanced consideration of thromboembolic and bleeding risk. Materials & methods: A retrospective cohort of nonvalvular atrial fibrillation patients were identified. Univariate logistic regression and conditional inference trees were used to quantify the importance of the CHA2DS2-VASc and modified HAS-BLED scores and their individual components on OAC treatment decisions. Results: The individual components of these risk scores provided more distinguishability between treated and untreated patients than the risk scores themselves, with bleeding risk factors strongly associated with nontreatment. Conclusion: While individual components of risk scores drive OAC treatment decisions according to guidelines, the relationship between bleeding risk factors and nontreatment warrants further consideration.

Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study.

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

British Thoracic Society Quality Standards for outpatient management of pulmonary embolism.

INTRODUCTION: The purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for outpatient management of pulmonary embolism in the UK, together with measurable markers of good practice. Quality statements are based on the British Thoracic Society (BTS) Guideline for the Initial Outpatient Management of Pulmonary Embolism. METHODS: Development of BTS Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards. RESULTS: Six quality statements have been developed, each describing a standard of care for the outpatient management of pulmonary embolism in the UK, together with measurable markers of good practice. DISCUSSION: BTS Quality Standards for Outpatient Management of Pulmonary Embolism form a key part of the range of supporting materials that the society produces to assist in the dissemination and implementation of a guideline's recommendations.

Factors associated with non-prescription of oral anticoagulant treatment in non-valvular atrial fibrillation patients with dementia: a CPRD-HES study.

Dementia is a common comorbidity in patients with atrial fibrillation (AF) and treatment guidelines recommend oral anticoagulant (OAC) therapy for AF patients with dementia unless concordance cannot be ensured by the caregiver. Despite this, the literature reports a low prescribing of OAC treatment in these patients. This study investigated possible factors associated with non-prescribing of OAC treatment in dementia patients newly diagnosed with non-valvular atrial fibrillation (NVAF) at age ≥ 65 years between 2013 and 2017 using the Clinical Practice Research Datalink and Hospital Episodes Statistics databases. Of 1090 dementia patients newly diagnosed with NVAF, 693 (63.6%) patients did not have a prescription for an OAC in the year following their diagnosis. The likelihood of experiencing a thromboembolic event was high, with 97% of the population having a CHA2DS2-VASc score > 2; however, little difference in the presence of stroke risk factors was observed between the prescribed and non-prescribed groups. The presence of bleeding risk factors was high; only 28 (2.6%) of patients did not have a previous fall or a HAS-BLED bleeding risk factor. A history of falls [OR = 0.76, 95% confidence intervals (CIs) (0.58, 0.98)], previous major bleed [OR = 0.56, 95% CI (0.43, 0.73)] and care home residence [OR = 0.47, 95% CI (0.30, 0.74)] were associated with not having an OAC prescription. The results suggest that dementia patients with NVAF and certain risk bleeding risk factors are less likely to be prescribed an OAC. Further work is needed to establish possible relationships between bleeding risk factors and other potential drivers of OAC prescribing.

Suspected cancer symptoms and blood test results in primary care before a diagnosis of lung cancer: a case-control study.

Aim: To compare symptoms and blood test results prior to cancer diagnosis in individuals who developed lung cancer and those who did not. Patients & methods: Nested case-control study, lung cancer patients were matched to up four controls with no record of cancer. Differences in symptoms and blood test results were investigated in the 2-year period prior to diagnosis. Results: 26,379 lung cancer patients were matched to 92,125 controls. Elevated C-reactive protein (CRP) was independently predictive of lung cancer at every 2-month interval 12 months prior to diagnosis. Elevated CRP in conjunction with at least one symptom was associated with greater than fourfold higher odds of lung cancer. Conclusion: CRP may be a prediagnostic marker for lung cancer, and when present with other symptoms could facilitate the investigation of high-risk individuals.

Risk of Recurrent Bleeding Events in Nonvalvular Atrial Fibrillation Treated with Vitamin K Antagonists: A Clinical Practice Research Datalink Study.

Background There is little evidence on how the occurrence of a bleed in individuals on vitamin K antagonists (VKAs) impacts the risk of subsequent bleeds, and thromboembolic and ischemic events. Such information would help to inform treatment decisions following bleeds. Objective To estimate the impact of bleeding events on the risk of subsequent bleeds, venous thromboembolism (VTE), stroke, and myocardial infarction (MI) among patients initiating VKA treatment for new-onset nonvalvular atrial fibrillation (NVAF). Methods We conducted an observational cohort study using a linked Clinical Practice Research Datalink-Hospital Episode Statistics dataset. Among a cohort of individuals with NVAF, the risk of clinically relevant bleeding, VTE, stroke, and MI was compared between the period prior to the first bleed and the periods following each subsequent bleed. The rate and cost of general practitioner (GP) consultations, prescriptions, and hospitalizations were also compared across these periods. Results The risk of clinically relevant bleeding events was observed to be elevated at least twofold in all periods following the first bleeding event. The risk of VTE, stroke, and MI was not found to differ according to the number of clinically relevant bleeding events. The rate and cost of GP consultations, GP prescriptions, and hospitalizations were increased in all periods relative to the period prior to the first bleed. Conclusions The doubling in the risk of bleeding following the first bleed, taken alongside the stable risk of MI, VTE, and stroke, suggests that the risk-benefit balance for VKA treatment should be reconsidered following the first clinically relevant bleed.