Prior Bleeding Research Articles

Abstract 4136743: Current Oral Anticoagulation Use Among Patients With Atrial Fibrillation and Risk Factors Associated With Inadequate Treatments: A Report From a UK Population Cohort Study

Background: The worldwide prevalence of atrial fibrillation (AF) continues to grow with approximately 60 million cases each year. Aim: To understand demographic and clinical attributes of patients receiving adequate DOAC (direct oral anticoagulant) treatment, DOAC undertreatments, or no OAC (oral anticoagulant) treatments, thus providing valuable perspectives into the current landscape of stroke prevention in AF within the UK. Methods: We used the Clinical Practice Research Datalink (CPRD) Aurum database from January 2020 to March 2021 for this retrospective observational study. Patients’ characteristics from various cohorts (standard dose [SD], low dose [LD] per label, LD inconsistent per label prescribing, and untreated) were evaluated based on OAC treatment. Duration of index OAC treatment, time to discontinuation and incidence rates across OAC treated cohorts were assessed. A machine learning method (Elastic Net) identified factors associated with being undertreated or untreated. Results: The final sample included 13,341 patients (mean age 78.5 and female 47%). Within a 180-day timeframe post-diagnosis, 76% of patients received OAC treatment, while 24% did not receive any OAC therapy. Among those treated with DOAC (n=9947), 74% were administered SD (n=7238), 18% received LD per labels (n=1756) and 10% were inappropriately prescribed LD of DOACs (n=953). Both LD cohorts tended to have shorter duration of OAC therapy (figure) and higher discontinuation rates (per 100 person-years; LD per label: 42.97; LD not per label: 39.11) compared to the SD cohort (SD: 31.67). Patients who were untreated were associated with elevated bleeding risk factors such as renal disease and prior bleeding history; patients who received inappropriate LD were associated with age above 75, renal disease, GI conditions with PPI (proton pump inhibitor) concomitant treatments when compared to SD cohort. Conclusions: In our study, a considerable proportion of AF patients remained untreated/undertreated and were associated with bleeding risk factors, highlighting the unmet needs within this population. Exploring potential alternative treatment options with enhanced safety profiles could offer substantial benefits to patients in need.

The impact of targeted bleeding source treatment on the risk of recurrent bleeding after percutaneous coronary intervention among patients with a history of prior bleeding

Abstract Background Prior bleeding is one of the strongest predictors for bleeding after percutaneous coronary intervention (PCI). Whether targeted treatment of the prior bleeding site affects the risk of bleeding after PCI is unknown to date. Methods From an all-comers population undergoing PCI between 2009-2019, patients with BARC 2-4 bleeding prior to index PCI were identified. Among those, the recurrence of BARC 2-5 bleeding at the same bleeding site, any BARC 2-5 bleeding, and mortality were compared throughout 1 year after PCI between patients with vs. without targeted treatment at the prior bleeding site. Targeted treatment was defined as medical, interventional, or surgical therapy targeted to cure the cause of bleeding. Adjusted hazard ratios (HRadj) were extracted from Cox regressions. Inverse probability weights were computed from a logistic regression with targeted treatment as dependent variable, and the following covariates: ARC-HBR variables associated with ≥4% 1-year bleeding risk in this registry (including oral anticoagulation), aspirin, potent P2Y12 inhibitor treatment, and prior bleeding site. Results Out of 18’510 patients enrolled from 2009-2019, 845 (4.6%) had a history of prior BARC 2-4 bleeding before PCI. Mean age was 71.6 years, 25% were female, and 52% presented with acute coronary syndrome. Patients with targeted treatment were significantly younger (70.3 vs. 72.5 years, p=0.005) and had more frequently malignancies (25% vs. 18%, p=0.012). 26/344 (7.6%) of patients with targeted treatment vs. 31/501 (6.2%) of patients without targeted treatment experienced recurrent BARC 2-5 bleeding at the same bleeding site (HRadj 1.35, 95% CI 0.79-2.30, p=0.268). 45/344 (13.1%) of patients with targeted treatment vs. 59/501 (11.8%) of patients without targeted treatment experienced any recurrent BARC 2-5 bleeding (HRadj 1.16, 95% CI 0.78-1.72, p=0.473). The rate of mortality was also similar between the groups (targeted treatment 13.7% vs. no targeted treatment 12.4%, HRadj 1.13, 95% CI 0.76-1.67, p=0.549). Conclusions Among patients with a bleeding history before PCI, half of the recurrent bleeding events throughout 1-year after PCI occurred at the same bleeding site, regardless of whether the bleeding source underwent targeted treatment. These findings imply that targeted treatment is not protective for recurrent bleeding events after PCI and that prior bleeding represents rather a systemic than local bleeding risk.Frequency of bleeding sitesKaplan Meier curves

Anticoagulation and stroke in hospitalized patients newly diagnosed with secondary atrial fibrillation: a population-based cohort study

Abstract Background Atrial fibrillation (AF) can be triggered by acute precipitants, with reversion to sinus rhythm after the stressor resolves. This has been described as "secondary AF", to differentiate it from AF without acute provocation ("primary AF"). Objective To describe anticoagulation patterns and the risk of stroke following hospitalization with a new diagnosis of secondary AF, with comparison to a first hospitalization for primary AF. Methods We created a cohort of adults aged ≥66 years who were discharged alive from hospital after a first diagnosis of AF between April 1, 2013, and March 31, 2019. The main exposure was "secondary" AF, with "primary" AF serving as the comparator group. This was based on a validated approach utilizing the AF discharge diagnosis type. Patients were followed for 1 year. We used drug dispensation records to determine the proportion of people anticoagulated after discharge from hospital. We also identified hospitalizations for stroke. We used the cumulative incidence function to estimate the risk of stroke while not anticoagulated, while censoring on dispensation of anticoagulation and treating death as a competing risk. Inverse probability of censoring weights were used to reduce bias from informative censoring. Cause-specific hazards regression was used to estimate the hazard ratio (HR) for stroke associated with secondary AF (relative to primary AF) while accounting for differences in baseline characteristics and time-varying anticoagulation status. Results We identified 13,011 people with secondary AF and 11,065 with primary AF. People with primary AF were older (mean 79.5 yrs vs. 77.1 yrs for secondary AF), more likely to be female (58.6% vs. 42.3% for secondary AF), and more likely to have prior HF. Secondary AF was positively associated with prior bleeding, diabetes, ischemic heart disease, and peripheral vascular disease. Mortality was higher for people with secondary vs. primary AF: 1.7% (95%CI 1.5%-2.0%) vs. 0.7% (95%CI 0.6%-0.9%) respectively at 7 days, 4.2% (95%CI 3.9%-4.6%) vs. 2.5% (95%CI 2.2%-2.8%) at 30 days, and 16.1% (95%CI 15.5%-16.7%) vs. 14.6% (13.9%-15.2%) at 1-year post-discharge. The proportion of people who were dispensed anticoagulants within 7 days of discharge was lower for secondary than primary AF (26.9% vs. 68%), and this continued to be lower at one year (41.7% vs. 82.3%, p<0.001 for both comparisons). At 1 year, the risk of stroke in people who were not anticoagulated was 2.2% (95% CI 1.6-2.8%) after primary AF and 1.2% (95% CI 1.0-1.4%) after secondary AF (p< 0.001). Relative to patients with primary AF, the hazard of stroke (adjusted for baseline characteristics and time-varying anticoagulation status) was lower in patients with secondary AF (HR 0.74; CI 0.57-0.97; p= 0.03). Conclusion Secondary AF is associated with higher mortality, less anticoagulation, and a lower risk/ hazard of stroke than primary AF. These data can inform post-discharge care in people with secondary AF.Proportion anticoagulated over timeRisk of stroke without anticoagulation

Evaluation of the biomarker-based ABC-AF-bleeding risk score and clinically based bleeding scores in 31,605 patients with atrial fibrillation treated with oral anticoagulation

Abstract Background International guidelines recommend a systematic evaluation of bleeding risk in patients with atrial fibrillation (AF) to guide oral anticoagulation. However, it remains challenging to accurately predict bleeding risk. The biomarker-based ABC-AF-bleeding risk score to predict bleeding in anticoagulated patients with AF has shown promise. Purpose To evaluate the performance of the biomarker-based ABC-AF-bleeding risk score and compare its performance with other bleeding risk scores in 31,605 patients randomized to direct oral anticoagulant or warfarin using individual patient data from three randomized clinical trials. Methods The COMBINE AF biomarker data set contains individual patient data from three pivotal randomized trials (ARISTOTLE, ENGAGE AF-TIMI 48, and RE-LY) comparing apixaban, edoxaban or dabigatran with warfarin, in patients with AF at increased risk of stroke. The ABC-AF-bleeding biomarkers were analyzed in plasma samples collected at baseline (hemoglobin, troponin T high-sensitivity, and GDF-15) using Roche Diagnostics Elecsys assays. The biomarker-based ABC-AF-bleeding risk score (Age, Biomarkers, Clinical history of prior bleeding) was calculated as previously published. The discrimination was assessed by Harrell’s c index and compared with three clinically based bleeding risk scores; HASBLED, ORBIT, and DOAC. Results During a median follow-up time of 2.0 years, a total of 1,572 ISTH major bleeding events occurred (incidence rate per 100 person-years of 2.79) including 593 gastrointestinal (1.04) and 270 intracranial (0.47) bleeding events. The biomarker-based ABC-AF-bleeding score was well calibrated for major bleeding in the total material (Figure). The c indices for major bleeding were 0.68 (95% confidence interval 0.67-0.70), for gastrointestinal bleeding 0.70 (0.68-0.72), and for intracranial bleeding 0.66 (0.63-0.69). The biomarker-based ABC-AF-bleeding risk score provided superior discrimination compared with the clinically based risk scores in the full cohort (Table). The ABC-AF-bleeding risk score also provided superior discrimination for major bleeding in clinically relevant subgroups based on age, sex, body mass index, coronary artery disease, diabetes, heart failure, kidney function, and irrespective of DOAC or VKA use. Conclusions In patients with AF treated with different types of OAC the biomarker-based ABC-AF-bleeding score provide better discrimination of the risk för major bleeding than risk scores based only on clinical factors. The results were consistent for different types of bleeding and across multiple subgroups. There was good calibration when comparing predicted vs observed rate of major bleeding. These findings support the utility of the biomarker-based ABC-AF-bleeding risk score for advancing precision medicine in patients with AF.Calibration of ABC-AF-bleeding scoreTable

Clinical predictors of warfarin-associated bleeding: A case-control study.

Despite the advent of directly acting oral anticoagulants, warfarin is still widely used in resource-poor settings. Bleeding as a result of warfarin overdosage is common and risk factors seem to vary between patient populations. Predictors of bleeding in patients using warfarin were studied using a case-control design. We calculated the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol (HAS-BLED) score (a bleeding risk prediction tool). Cases chosen were adults prescribed warfarin presenting with bleeding and controls were likewise taking warfarin but had no bleeding in the previous six months. The most common indication for warfarin use was venous thromboembolism. Recent decrease in food intake was strongly associated with bleeding. Older age, higher warfarin doses, recent illness in the past fortnight and prior bleeding were also independent predictors. A higher HAS-BLED score was not predictive independently. Closer monitoring of international normalised ratio is therefore advisable during acute illnesses and in those with decreased food intake.

Long-Term Clinical Outcomes Following the WATCHMAN Device Use in Medicare Beneficiaries.

Long-term outcomes following left atrial appendage occlusion outside clinical trials and small registries are largely unknown. Collecting these data was a condition of US market authorization of the WATCHMAN device. The aim of this analysis was to evaluate the rates of stroke, bleeding, and death among Medicare beneficiaries following left atrial appendage occlusion implantation during initial commercial availability of the WATCHMAN left atrial appendage occlusion device overall and in important subgroups. All Medicare fee-for-service beneficiaries ≥65 years of age who underwent left atrial appendage occlusion from April 1, 2016, to August 31, 2020, were included based on the International Classification of Diseases, Tenth Revision, and Current Procedural Terminology codes. Over a 5-year follow-up period, the cumulative incidence over time of mortality, ischemic stroke, and major bleeding were calculated using the International Classification of Diseases, Tenth Revision, diagnosis codes for the full study cohort and within important prespecified subgroups. WATCHMAN recipients (n=48 763) were a median of 77 (interquartile range, 72-82) years of age, 42% female, and mostly White (93%). The median CHA2DS2VASc score was 4 (interquartile range, 3-5) with prior major bleeding in 42% and prior stroke in 12%. At 5 years, death occurred in 44%, bleeding in 15% (with higher risk early following implantation), and ischemic stroke in 7%. Each of these end points was more common with greater baseline age. Male patients had greater 5-year mortality than female patients (46.9% versus 40.6%), but there was no difference between sexes in the rates of ischemic stroke (6.6% versus 7.5%) or major bleeding (14.9% for both). WATCHMAN recipients with prior ischemic stroke or a major bleeding event were older and frailer; these groups had higher rates of ischemic stroke, major bleeding, and death. Compared with patients enrolled in the pivotal clinical trials, Medicare beneficiaries undergoing WATCHMAN implantation were older, more female, and had more comorbid conditions. Substantial long-term mortality and major bleeding following WATCHMAN reflect the high-risk nature of the patient population, while the ischemic stroke rate was relatively low (<1.5% per year).

Acquired hemophilia A as a disease of the elderly: A comprehensive review of epidemiology, pathogenesis, and novel therapy

AbstractAcquired hemophilia A (AHA) is a rare autoimmune bleeding disorder characterized by the development of neutralizing autoantibodies (inhibitors) against coagulation factor VIII (FVIII). This review provides an in-depth exploration of AHA, covering its epidemiology, pathogenesis, clinical presentation, diagnosis, complications, and treatment strategies, focusing on recent advancements. AHA can manifest in both men and women with no prior bleeding history. The annual incidence is estimated to be approximately 1 case per million individuals in the general population. The incidence increases significantly with age: the incidence among individuals aged 60 years or older is approximately 3 to 4 cases per million individuals per year. Typically, patients present with an acquired bleeding disorder that is characterized by an isolated, prolonged activated partial thromboplastin time stemming from FVIII deficiency. Diagnosis relies on the detection of neutralizing antibodies using the Nijmegen-modified Bethesda assay. Hemostatic control strategies involve bypassing agents like recombinant activated factor VII, activated prothrombin complex concentrate, and recombinant porcine FVIII for bleeding patients. Emicizumab, a novel bypassing agent, exhibits several potential advantages. In the realm of immunosuppressive treatment for inhibitor eradication, the CyDRi regimen emerged as a remarkable advancement, significantly enhancing the outlook for the management of AHA even in the elderly frail population.

Oral anticoagulation in patients with hypertrophic cardiomyopathy and non‐valvular atrial fibrillation in Japan

AbstractAimsThere are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non‐valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan.MethodsThis retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest‐neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE).ResultsAfter PS matching, 2955 DOAC‐ and 1603 warfarin‐treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with β‐blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50–1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78–1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47–0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22–3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10–3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05–4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22–2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24–2.83).ConclusionsDOAC‐treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin‐treated patients. Prior stroke was shown to augment stroke risk by approximately three‐fold. This large real‐world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan.

Bleeding recurrence risk among hospitalized patients undergoing therapeutic plasma exchange: a multi-center study.

In hospitalized patients undergoing therapeutic plasma exchange (TPE), it is not known how TPE-associated bleeding risk is impacted by a prior bleeding episode. Therefore, to assess the prevalence and predictors of bleeding recurrence, we analyzed data from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). Using a retrospective cross-sectional analysis of REDS-III public use files, we identified hospitalized adults who had a major bleeding episode prior to their first TPE procedure. Patients were classified into two cohorts based on bleeding recurrence (no-recurrence vs recurrence). After identifying potential predictors, we used multiple imputation by chained equations to impute variables with <30% missing data. Variable selection was optimized using a 10-fold cross validated least absolute shrinkage and selection operator. Final predictors were identified by fitting a logistic regression model. In 310 patients with major bleeding prior to TPE initiation, bleeding recurred in 121 (39.0%). We identified the following seven unique predictors: 1) >10 TPE procedures (OR 2.23); 2) intensive care unit stay (OR 1.35); 3) thrombocytopenia (OR 1.26); 4) surgery (OR 1.22); 5) hepatic disease (OR 1.21); 6) 6-10 TPE procedures (OR 1.04); and 7) Asian race (OR 1.01). We also identified the following five interactions: 1) surgery and therapeutic anticoagulation (OR 1.50); 2) 6-10 TPE procedures and therapeutic anticoagulation (OR 1.05); 3) 6-10 TPE procedures and antiplatelets (OR 1.02); 4) >10 TPE procedures and antiplatelets (OR 1.00); and 5) albumin-only TPE and antiplatelets (OR 0.53). When assessed for adjusted performance, the prediction model had a C-statistic of 0.617 (95% CI 0.613-0.619) and Brier Score of 0.342 (95% CI 0.340-0.347). In this study assessing predictors of bleeding recurrence among hospitalized patients undergoing TPE, we identified seven variables and five interactions. These findings should be validated in future studies.

The Association of Hematological Markers with Occurrence of Thrombotic and Bleeding Events following Left Atrial Appendage Occlusion.

Patients undergoing left atrial appendage occlusion (LAAO) are at increased risk for bleeding or thromboembolic events. Concurrently, biomarkers are of growing importance in risk stratification for atrial fibrillation patients. We aimed to evaluate the association of hematological markers and clinical characteristics with the occurrence of thromboembolic and bleeding events following LAAO. Seven implanting centers retrospectively gathered data on hematological markers (i.e., platelet count [PC], mean platelet volume [MPV], and fibrinogen) prior to LAAO. Prespecified thromboembolic and major bleeding outcomes were collected and the association with pre-procedural hematological markers and clinical characteristics was evaluated using Cox regression analysis. In total, 1,315 patients were included (74 ± 9 years, 36% female, CHA2DS2-VASc 4.3 ± 1.5, HAS-BLED 3.3 ± 1.1). Over a total follow-up duration of 2,682 patient years, 77 thromboembolic events and 107 major bleeding events occurred after LAAO. Baseline PC was the only biomarker showing a signal for a relation to thromboembolic events (HR 1.18, 95% CI: 1.00-1.39) per 50*109 increment, p = 0.056). Thrombotic event rates, including device-related thrombus, increased within higher PC quartiles. Thromboembolism was associated with age (HR 1.05, 95% CI: 1.00-1.10, per year increase) and prior thromboembolism (HR 2.08, 95% CI: 1.07-4.03), but with none of the biomarkers in multivariate analysis. No association of any of the hematological markers with major bleeding was observed. Major bleeding following LAAO was associated with prior major bleeding (HR 5.27, 95% CI: 2.71-10.22), renal disease (HR 1.93, 95% CI: 1.17-3.18), and discharge on dual antiplatelet therapy (DAPT) (HR 1.71, 95% CI: 1.05-2.77). Most thrombotic events occurred in the highest PC quartile, but no association of any of the hematological markers with thromboembolism or major bleeding was observed in our analysis. In multivariate analysis, older age and prior thromboembolism were associated with thromboembolism. Prior major bleeding, renal disease and discharge on DAPT were multivariate predictors of major bleeding after LAAO.

Early Nonprocedural Bleeding After Left Atrial Appendage Occlusion

BackgroundPatients treated with left atrial appendage occlusion (LAAO) are at high bleeding risk. Intensive antithrombotic treatment is recommended after the procedure to prevent device-related thrombosis. ObjectivesThis study sought to evaluate the incidence, consequences, and predictors of early nonprocedural bleeding after LAAO. MethodsThis was a multicenter study including 1,649 patients undergoing LAAO in 9 centers. Early nonprocedural bleeding was defined as bleeding unrelated to the procedure occurring within 3 months after device implantation. The severity of bleeding was defined by the Valve Academic Research Consortium-2 classification. A sensitivity analysis was performed at 45 days. ResultsA total of 121 (7.3%) patients experienced early nonprocedural bleeding events, and 69 (57.0%) were classified as major bleeding (4.2% of patients). Independent predictors of early nonprocedural bleeding were dual antiplatelet therapy (DAPT) at discharge (adjusted HR [aHR]: 1.61; 95% CI: 1.12-2.33; P = 0.01), prior gastrointestinal bleeding (aHR: 2.15; 95% CI: 1.38-3.35; P < 0.001), and multiple locations of prior bleeding (aHR: 2.33; 95% CI: 1.34-4.05; P < 0.001). DAPT at discharge was predictive of both all and major nonprocedural bleeding at 3 months and 45 days. After a median follow-up of 2.3 years (Q1-Q3: 1.1-4.1 years), early nonprocedural bleeding was independently associated with an increased risk of all-cause death (aHR: 1.53; 95% CI: 1.15-2.06; P < 0.001). This heightened mortality risk was similar at 45 days. ConclusionsEarly nonprocedural bleeding after LAAO occurred in ∼7% of patients within 3 months, with more than one-half being classified as major bleeding. Regardless of severity, early nonprocedural bleeding was associated with increased mortality. DAPT at discharge determined an increased risk of early nonprocedural bleeding after LAAO. These results emphasize the importance of bleeding risk for determining antithrombotic strategies after LAAO.

Development and internal validation of the Cleveland Clinic Bleeding Model to predict major bleeding risk at admission in medical inpatients

BackgroundGuidelines recommend pharmacologic VTE prophylaxis for acutely ill medical patients at acceptable bleeding risk, but only the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) model has been validated for bleeding risk assessment. ObjectivesWe developed and internally validated a risk assessment model (RAM) to predict major in-hospital bleeding using risk factors at admission and compared our model with IMPROVE. MethodsWe selected patients admitted to medical services at 10 hospitals in the Cleveland Clinic Health System from 2017 to 2020. We identified major bleeding according to the International Society on Thrombosis and Haemostasis criteria, using a combination of diagnostic codes and laboratory values, and confirmed events with chart review. We fit a least absolute shrinkage selection operator logistic regression model in the training set and compared the discrimination and calibration of our model with the IMPROVE model in the validation set. ResultsAmong 46 314 admissions, 268 (0.58%) had a major bleed. The final RAM included 16 risk factors, of which prior bleeding (odds ratio [OR] = 4.83), peptic ulcer (OR = 3.82), history of sepsis (OR = 3.26), and steroid use (OR = 2.59) were the strongest. The Cleveland Clinic Bleeding Model had better discrimination than IMPROVE (area under the receiver operating characteristics curve = 0.85 vs 0.70; P < .001) and, at equivalent sensitivity (52%), categorized fewer patients as high risk (7.2% vs 11.8%; P < .001). Calibration was adequate (Brier score = 0.0057). ConclusionUsing a large population of medical inpatients with verified major bleeding events, we developed and internally validated a RAM for major bleeding whose performance surpassed the IMPROVE model.

Percutaneous left atrial appendage closure for stroke prevention in hypertrophic cardiomyopathy patients with atrial fibrillation

BackgroundPercutaneous left atrial appendage closure (LAAC) is an effective alternative strategy for stroke prevention in patients with atrial fibrillation (AF) at high risk for bleeding with anticoagulation (AC). Efficacy of this strategy in hypertrophic cardiomyopathy (HCM) remains uncertain. ObjectiveThe study aimed to compare risk of stroke in HCM-AF patients treated with LAAC with those treated with AC. MethodsBy use of the TriNetX Global Research Network, HCM-AF patients from 2015 to 2024 were assigned to categories of treatment with LAAC and treatment solely with AC and observed for 3 years for ischemic stroke, systemic embolism, and all-cause mortality. Propensity score matching was used to limit confounders. ResultsOf 14,867 HCM-AF patients identified, 364 (2.5%) were treated with LAAC vs 14,503 (97.5%) treated with AC. HCM LAAC patients were older (72 vs 67 years; P < .001) and had more comorbidities and more prior bleeding events, including higher rate of prior gastrointestinal bleeding (68% vs 18%; P < .001), compared with HCM patients treated solely with AC. After propensity score matching, there was no baseline difference between groups including prior bleeding events (P > .05). During follow-up, HCM patients treated with LAAC had higher rates of ischemic stroke (13% vs 8%; hazard ratio, 1.9; P = .006) and systemic embolism (14% vs 9%; hazard ratio, 1.8; P = .006) but no difference in mortality compared with matched HCM patients receiving AC. ConclusionThese real-world data do not support percutaneous LAAC in HCM-AF patients as the primary treatment strategy during long-term AC to reduce stroke risk. However, LAAC may remain a reasonable option for HCM-AF patients who are unable to tolerate AC because of prohibitive bleeding risk.

Safety and feasibility of atrial fibrillation ablation after left atrial appendage closure: A single-center experience of the left atrial appendage closure first strategy.

Patients with atrial fibrillation (AF) who are not suitable for long-term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC). The safety and feasibility of left atrial catheter ablation (CA) procedures after LAAC remain unclear. This study aimed to clarify the feasibility and safety of CA after LAAC, including in the early phase within 180 days. Characteristics and clinical outcomes of 46 patients with AF who had undergone both CA and LAAC within 2 years (mean age, 72 years; 29 men) were compared between those who had undergone CA-first (31 patients) and LAAC-first (15 patients). The mean CHA₂DS₂-VASc and HAS-BLED scores were 4.8 and 3.3 points, respectively. The LAAC-first strategy was often used in patients with prior major bleeding and LAA thrombosis or sludge. In the LAAC-first group, the mean duration between both procedures was 212 days, and all LAAC-first patients, including seven patients in the early phase, could undergo CA without LAAC device-related complications; moreover, no cardiovascular adverse events were reported after both procedures (mean periods: 420 days). After CA post-LAAC, no device-related adverse events (device-related thrombosis, new peri-device leak appearance, peri-device leak increase, or device dislodgement) were observed, whereas, after LAAC post-CA, 3 new peri-device leak appearance events and 1 peri-device leak increase event were observed, especially patients who underwent LAAC in the early phase post-CA. Based on single-center experience, left atrial CA in the presence of an LAAC device implanted including the early phase was safe and feasible.

Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis

Gastrointestinal (GI) bleeding control is critical in elderly patients with atrial fibrillation (AF) receiving oral anticoagulants (OAC). This subgroup analysis aimed to clarify the actual state and significance of GI bleeding in elderly non-valvular AF (NVAF) patients. We evaluated the incidence and risk factors of GI bleeding during the 2-year follow-up and examined the GI bleeding impact on mortality. Of the 32,275 patients in the ANAFIE Registry, 1139 patients (3.5%) experienced GI bleeding (incidence rate, 1.92 events per 100 person-years; mean follow-up, 1.88 years); 339 upper and 760 lower GI bleeding events occurred. GI bleeding risk factors included age ≥ 85 years, body mass index ≥ 25.0 kg/m2, prior major bleeding, hyperuricaemia, heart failure, P-glycoprotein inhibitor use, GI disease, and polypharmacy (≥ 5 drugs). No significant differences in GI bleeding risk were found between direct OAC (DOAC) vs warfarin users (adjusted hazard ratios [95% confidence interval], 1.01 [0.88–1.15]). The 1-year post-GI bleeding mortality rate was numerically higher in patients with upper (19.6%) than lower GI bleeding (8.9%). In elderly Japanese NVAF patients, this large-scale study found no significant difference in GI bleeding risk between DOAC vs. warfarin users or 1-year mortality after upper or lower GI bleeding.

PRECISE-DAPT, ARC-HBR, or Simplified Clinical Evaluation for the Prediction of Major Bleeding After Percutaneous Coronary Intervention in older Patients

Elderly patients have been remarkably under-represented in bleeding risk cohorts. Thus, the PRECISE-DAPT and ARC-HBR scores are not validated in older adults. Therefore, we sought to evaluate the PRECISE-DAPT and ARC-HBR scores in an exclusively elderly population and furthermore assess the prognostic value of a truly simplified clinical evaluation (SCE), consisting of only 3 binary clinical variables (hemoglobin <11g/dL, prior bleeding and anticipated use of anticoagulants). This is a retrospective analysis of the prospective single-center Elderly-HCD registry. Consecutive patients of ≥75 years of age that underwent percutaneous coronary intervention in the period of 2012-2019 were included. The primary endpoint was post discharge bleeding (PDB) at 12 months follow-up, defined according to the BARC 3/5 criteria. A total of 693 patients with a mean age of 81 (± 4.4) years were included in the study and 60 (6.8%) patients met the primary endpoint. The PRECISE-DAPT and ARC-HBR scores did not significantly predict PDB in Cox-regression models (HR: 1.65 (0.78-3.42) and 1.46 (0.72-4.24), respectively), whereas the SCE outperformed both scores (HR: 2.47 (1.34-4.49)). All 3 scores exhibited a moderate discriminatory potential as determined by ROC-curve analysis (AUCs 0.601, 0.621 and 0.616, respectively) with no significant differences when comparing either of them. The SCE showed an IDI of 0.25, p=0.02 (SCE vs ARC-HBR) and 0.24, p=0.01 (SCE vs PRECISE-DAPT); with NRI of 6.54%, p=0.37 and 7.12%, p=0.43, respectively. In conclusion, both the PRECISE-DAPT score and ARC-HBR criteria showed insufficient predictive value in older adults. A truly SCE, consisting of 3 easily accessible variables, not only provides equal discriminatory potential but also demonstrates superior predictive value as determined by cox-regression models. This makes it a highly appealing tool for risk stratification, pending its evaluation in larger prospective studies.

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and active cancer who also had prior bleed or prior renal disease

Objective Patients with active cancer and venous thromboembolism (VTE) have elevated risk of recurrent VTE (rVTE) and major bleeding (MB). The risk is even higher within those with a prior bleeding event or renal disease. There is a need to understand the risk of rVTE and MB of commonly used anticoagulants among these high-risk patients. Methods VTE patients with active cancer and treated with apixaban, warfarin, or low molecular weight heparin (LMWH) within 30 days of VTE were identified from five claims databases in the United States. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. The post-IPTW population was stratified by prior bleed or renal disease status. Cox proportional hazards models were used to evaluate interactions between treatment and prior bleed or renal disease on risk of rVTE and MB, with p value <.1 considered significant. Results Study criteria were met by 30,586 VTE cancer patients: 35.0% had prior bleed and 29.0% had renal disease. For apixaban, LMWH, and warfarin cohorts, the incidence (events per 100 person-years) of MB was higher in patients with prior bleed (17.48 vs 7.58, 25.61 vs 13.11, and 20.38 vs 8.97) or renal disease (15.79 vs 8.71, 22.11 vs 15.90, and 18.49 vs 10.39) vs those without the conditions. Generally, there were no significant interactions between anticoagulant use and prior bleed or renal disease on rVTE and MB (p for interaction >.1). Conclusion The incidence of MB was higher among those with prior bleed or renal disease. Effects of apixaban, warfarin, or LMWH were generally consistent regardless of prior bleed or renal disease status.

Bleeding and Thrombotic Outcomes in Adults with Cancer-Associated Splanchnic Vein Thrombosis and Thrombocytopenia

Introduction: Splanchnic vein thrombosis (SVT) can arise as a complication in patients with underlying cancers, especially gastrointestinal malignancies, as well as other comorbidities such as liver disease. In patients with cancer-associated thrombosis, thrombocytopenia is a common co-occurrence that can complicate management decisions around anticoagulation. Data on the optimal management of SVT in patients with malignancies is limited, and the risk of bleeding and recurrent thrombosis in patients with cancer-associated SVT and thrombocytopenia is unclear. Methods: We identified patients with radiographic diagnosis of cancer-associated SVT at our institution between 2010 and 2021. Exclusion criteria included squamous and basal cell carcinomas and myeloproliferative neoplasms. We manually reviewed all medical records to determine baseline clinical data and clinical outcomes. We performed log-binomial regression to identify independent risk factors for major bleeding, using age at thrombosis (continuous), gender, prior major bleed, baseline creatinine (continuous), use of antiplatelets, and use of anticoagulants as covariates. We present these data as adjusted risk ratios (RR) and 95% confidence intervals (CI). We subsequently used Cox models with inverse probability of treatment weighting with propensity scores for thrombocytopenia (platelet count less than 100,000/uL within 15 days before or after diagnosis of SVT) to calculate hazard ratios (HR) and 95% CIs for our outcomes of interest. Independent variables used in propensity scoring included all variables included in the adjusted models plus type of cancer (hematologic, solid tumor). Outcomes included major bleeding, clinically relevant non major bleeding (CRNMB), clinically relevant bleeding (major bleeding + CRNMB), progression and recurrence of SVT, and development of usual-site VTE (DVT or PE) up to one year following the initial SVT. Progression was defined as extension of the thrombus contiguously into a new vein, and recurrence was defined as a new interval thrombus which was non-contiguous with the initial thrombus. Results: A total of 581 patients with cancer and SVT were identified. Baseline demographics, clinical history, laboratory data, and details of SVT are shown in Table 1. Of note, 44.2% of patients had cirrhosis, and the most common cancer types were hepatobiliary (55.2%) and pancreatic (22.0%); 40.7% of patients had metastatic disease. Of 512 patients with available platelet count data, 39.5% of patients had platelet count &amp;lt;100,000/uL; of these 512, 14.1% were &amp;lt;75,000/uL, and 12.7% were &amp;lt;50,000/uL. Most (70.6%) SVT were bland thrombi based on radiology interpretation, 19.9% were tumor thrombi, and 5.5% were mixed type, with the remainder being of uncertain etiology. Survival at one year was 41.5%, and median follow-up time was 5.5 months (interquartile range: 1.4-22.2). Only 4.0% of patients received a thrombectomy, and 39.2% were treated with anticoagulation within two weeks of diagnosis. The cumulative incidence of major bleeding event within one year of SVT diagnosis was 11.0% (95% CI: 8.5-13.5). This was primarily upper GI bleeding (70.3% of major bleeds). Multivariate regression analysis identified only male gender as an independent predictor of major bleeding (aRR: 0.91, 95% CI: 0.84-0.99), as shown in Table 2. In the propensity score-weighted Cox models, thrombocytopenia was not associated with an increased risk of major bleeding within one year (aHR: 1.65, 95% CI: 0.32-8.41). The cumulative incidence of CRNMB at one year was 6.7% (95% CI: 4.7-8.7), and cumulative incidence of clinically relevant bleeding was 17.7% (95% CI: 14.6-20.8). The cumulative incidence of progression or recurrence of SVT at one year was 16.3% (95% CI: 13.3-19.3). In the weighted Cox models, patients with thrombocytopenia did not impact the risk of progression or recurrence of SVT (aHR: 1.15, 95% CI: 0.58-2.26). The cumulative incidence of usual-site VTE at one year was 5.7% (95% CI: 3.8-7.5). Conclusion: Thrombocytopenia was a common co-occurrence in cancer-associated SVT. Major bleeding- especially upper GI bleeding- was a common complication of cancer-associated SVT. Recurrent or progressive SVT was also frequent, which highlights the challenges of optimal management in this high-risk population. We found that thrombocytopenia was not an independent risk factor for major bleeding in this population.

Left atrial appendage occlusion for atrial fibrillation and bleeding diathesis.

Patients with atrial fibrillation(AF) and likelihood of bleeding can undergo left atrial appendage occlusion (LAAO) as an alternative method of stroke prophylaxis. Short-term anti-thrombotic drugs are used postprocedure to offset the risk of device-related thrombus, evidence for this practice is limited. To investigate optimal postimplant antithrombotic strategy in high bleeding-risk patients. Patients with AF and high-risk for both stroke and bleeding undergoing LAAO were advised their perioperative drug therapy by a multidisciplinary physician panel. Those deemed to be at higher risk of bleeding from anti-thrombotic drugs were assigned to minimal treatment with no antithrombotics or Aspirin-alone. The remaining patients received standard care (STG) with a 12 week course of dual-antiplatelets or anticoagulation postimplant. We compared mortality, device-related thrombus, ischemic stroke, and bleeding events during the 90 days postimplant and long-term. Event-free survival was assessed using Kaplan-Meier survival analysis, with logrank testing for statistical significance. Seventy-five patientsunderwent LAAO of whom 63 patients(84%) had a prior serious bleeding event. The 42 patientson minimal treatment were older (74.3 ± 7.7 vs. 71.2 ± 7.2) with higher HASBLED score (3.6 ± 0.9 vs. 3.3 ± 1.2) than the 33 patientshaving standard care. There were no device-related thrombi or strokes in either group at 90 days postprocedure; STG had more bleeding events (5/33 vs. 0/42,p = 0.01) with associated deaths (3/33 vs. 0/42,p = 0.05). During long-term follow-up (median 2.2 years), all patients transitioned onto no antithrombotic drugs (43 patients [61%]) or a single-antiplatelet (29 patients[39%]). There was no evidence of early minimal treatment adversely affecting long-term outcomes. Short-term anti-thrombotic drugs may not be needed after LAAO implant in patients with high bleeding risk and could be harmful. Larger, prospective studies would be warranted to test these findings.

Risk of bleeding in patients with and without cancer on antiplatelet therapy following myocardial infarction: a study in primary care

Abstract Background Antithrombotic medication and antiplatelet therapy (ATPL) are used in the treatment and prevention of thrombotic disorders, especially in patients following a myocardial infarction (MI). However, the risk reduction of future ischaemic events must be balanced against the potential bleeding risk. Co-morbidities may predispose individuals to bleeding events. Cancer influences risk of bleeding either directly through bleeding of fragile cancer-associated blood vessels or by indirectly increasing the risk of bleeding remote from the cancer site. In patients with cancer, bleeding risk may be increased due to ATPL given for concomitant cardiovascular disease. Purpose To investigate the association between pre-existing cancer and risk of bleeding in patients on ATPL after myocardial infarction in a primary care population. Methods We performed a matched cohort analysis using data from the Clinical Practice Research Datalink (CPRD) and linked Hospital Episodes Statistics (HES) in England. People with an MI between 2006–2017 were matched to patients without an MI at a 1:5 ratio. Four groups: patients with both MI and cancer (breast, digestive tract, lung, prostate at baseline [within 1-year prior to MI]), patients with only cancer or MI; and patients without either condition. Using flexible parametric methods, hazard ratios were calculated to determine the association between patient group and risk of bleeding, as well as between APTL-regimen after MI and bleeding risk during 1-year of follow-up after MI. All data were processed using STATA/SE16, using a significance level of ≤0.05. Results We included 58,951 patients with an average (mean) age of 74±10 years (66% male). Of all patients, 12,526 (21%) patients had cancer, and 9,942 (17%) had an MI; numbers per subgroup are presented in Figure 1. A bleeding event was observed in 1,193 (2%) patients. The vast majority (N=56,148 [95%]) of patients did not take ATPL. Of those who did receive ATPL, aspirin was the most common (N=2,359 [4%]). In a multivariable model (adjusted for age, gender, ethnicity, prior bleeding, diabetes, renal disease, smoking status, drug, hypertension, hypercholesteraemia and cancer), people with MI had a risk (hazard) of bleeding of 2.52 (95% CI 2.23-2.86), p&amp;lt;0.001. For people with cancer only, the risk of bleeding was 1.26 (95% CI 1.10-1.44), p&amp;lt;0.001. Conclusion(s) Bleeding risks are higher in people with cancer after an MI than those with MI or cancer alone. More research is needed on individual anti-platelet therapies for people with cancer who have a MI to minimize the risk of bleeding and future cardiovascular events.Figure 1