Practice Patterns and Outcomes Associated With Anticoagulation Use Following Sepsis Hospitalizations With New-Onset Atrial Fibrillation.

BACKGROUND: Practice patterns and outcomes associated with the use of oral anticoagulation for arterial thromboembolism prevention following a hospitalization with new-onset atrial fibrillation (AF) during sepsis are unclear. METHODS: Retrospective, observational cohort study of patients ≥40 years of age discharged alive following hospitalization with new-onset AF during sepsis across 21 hospitals in the Kaiser Permanente Northern California health care delivery system, years 2011 to 2018. Primary outcomes were ischemic stroke/transient ischemic attack (TIA), with a safety outcome of major bleeding events, both within 1 year of discharge alive from sepsis hospitalization. Adjusted risk differences for outcomes between patients who did and did not receive oral anticoagulation within 30 days of discharge were estimated using marginal structural models fitted by inverse probability weighting using Super Learning within a target trial emulation framework. RESULTS: Among 82 748 patients hospitalized with sepsis, 3992 (4.8%) had new-onset AF and survived to hospital discharge; mean age was 78±11 years, 53% were men, and 70% were White. Patients with new-onset AF during sepsis averaged 45±33% of telemetry monitoring entries with AF, and 27% had AF present on the day of hospital discharge. Within 1 year of hospital discharge, 89 (2.2%) patients experienced stroke/TIA, 225 (5.6%) had major bleeding, and 1011 (25%) died. Within 30 days of discharge, 807 (20%) patients filled oral anticoagulation prescriptions, which were associated with higher 1-year adjusted risks of ischemic stroke/TIA (5.69% versus 2.32%; risk difference, 3.37% [95% CI, 0.36-6.38]) and no significant difference in 1-year adjusted risks of major bleeding (6.51% versus 7.10%; risk difference, -0.59% [95% CI, -3.09 to 1.91]). Sensitivity analysis of ischemic stroke-only outcomes showed a risk difference of 0.15% (95% CI, -1.72 to 2.03). CONCLUSIONS: After hospitalization with new-onset AF during sepsis, oral anticoagulation use was uncommon and associated with potentially higher stroke/TIA risk. Further research to inform mechanisms of stroke and TIA and management of new-onset AF after sepsis is needed.

Safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants and warfarin in patients on tuberculosis treatment.

Anti-tuberculosis treatment can cause significant drug-drug interaction and interfere with effective anticoagulation. However, there is a lack of evidence and conflicting data on the optimal oral anticoagulation in patients treated for tuberculosis. We investigated the safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients on anti-tuberculosis treatment. Patients on concomitant oral anticoagulation and anti-tuberculosis treatment including rifampin were identified from the Korean nationwide healthcare database. Subjects were censored at discontinuation of either anticoagulation or rifampin. The outcomes of interest were major bleeding, death, and ischemic stroke. A total 2090 patients (1153 on warfarin, 937 on NOAC) were included. NOAC users, compared to warfarin users, were older, had a lower prevalence of hypertension, heart failure, ischemic stroke, and aspirin use and a higher prevalence of cancer, with no significant differences in CHA2DS2-VASc or HAS-BLED scores. There were 18 major bleeding events, 106 deaths, and 50 stroke events during a mean follow-up of 2.9 months. After multivariable adjustment, the use of NOAC was associated with a lower risk of incident ischemic stroke (HR 0.51, 95% CI 0.27-0.94), while there was no significant difference in risk for major bleeding or death compared with warfarin. These results suggest that NOACs have better effectiveness for stroke prevention and similar safety compared with warfarin in patients on concomitant anti-tuberculosis treatment. This is the first study assessing the safety and effectiveness of NOACs compared to warfarin in this clinical scenario.

Association between hemorrhage and direct oral anticoagulants in combination with verapamil: Analysis of Japanese Adverse Drug Event Report database and electronic medical record data.

OBJECTIVE: The aim of this study was to investigate the risk of hemorrhage in concomitant therapy with direct oral anticoagulants (DOACs) and class IV antiarrhythmic drugs. MATERIALS AND METHODS: First, disproportionality analysis (DPA) was performed using the Japanese Adverse Drug Event Report (JADER) database to investigate the risk of hemorrhage with DOACs. Second, a cohort study was performed using electronic medical record data to confirm the results of the JADER analysis. RESULTS: In the JADER analysis, hemorrhage was significantly associated with treatment with edoxaban and verapamil (reporting odds ratio = 1.66; 95% confidence interval (CI) = 1.04 - 2.67). The cohort study revealed that hemorrhage incidence significantly differed between the verapamil-treated group and the bepridil-treated group, with a higher risk for hemorrhage in the verapamil group (log-rank test: p < 0.001). The multivariate Cox proportional hazards model also showed that the verapamil and DOAC combination was significantly associated with hemorrhage events compared with the bepridil and DOAC combination (hazard ratio (HR): 2.87, 95% CI: 1.17 - 7.07, p = 0.022). Furthermore, creatinine clearance (Ccr) ≥ 50 mL/min was significantly associated with hemorrhage events (HR: 2.72, 95% CI: 1.03 - 7.18, p = 0.043), and verapamil was significantly associated with hemorrhage in patients with Ccr ≥ 50 mL/min (HR: 3.58, 95% CI: 1.36 - 9.39, p = 0.010) but not in patients with Ccr < 50 mL/min. CONCLUSION: Verapamil increases the risk of hemorrhage in patients on DOACs. Dose adjustment of DOACs based on renal function may prevent hemorrhage when verapamil is concomitantly administered.

Bleeding Events After Transcatheter Aortic Valve Replacement: JACC State-of-the-Art Review.

Transcatheter aortic valve replacement (TAVR) has gained over time a major reduction in procedural complications. Despite this, clinically relevant bleeding still occurs in a non-negligible proportion of patients and adversely affects prognosis. Patients with severe aortic stenosis are at heightened risk for spontaneous bleeding due to advanced age and a high comorbidity burden. Also, procedural factors and antithrombotic management contribute to define individual bleeding susceptibility. Bleeding prevention represents an emerging area for improving patient care. Because of the tight hemorrhagic/ischemic balance, a tailored approach based on individual bleeding-risk profile, such as a less invasive antithrombotic regimen or appropriate diagnostic preprocedural evaluation, should be pursued to avoid bleeding events. This review aims to provide an in-depth overview of bleeding events in the TAVR field, including definitions, timing and the extent of risk, and clinical impact, as well as updates on antithrombotic management and its potential influence on bleeding complications.

P2Y12 Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions.

BACKGROUND: It remains unclear whether P2Y12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). OBJECTIVES: We sought to assess the effects of P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity. METHODS: We pooled patient-level data from randomized controlled trials comparing P2Y12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding. RESULTS: Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; Pinteraction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; Pinteraction = 0.920). CONCLUSIONS: P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853).

Comparative Effectiveness of Left Atrial Appendage Occlusion Versus Oral Anticoagulation by Sex.

BACKGROUND: The comparative real-world outcomes of older patients with atrial fibrillation (AF) treated with anticoagulation compared with left atrial appendage occlusion (LAAO) may be different from those in clinical trials because of differences in anticoagulation strategies and patient demographics, including a greater proportion of women. We sought to compare real-world outcomes between older patients with AF treated with anticoagulation and those treated with LAAO by sex. METHODS: Using Medicare claims data from 2015 to 2019, we identified LAAO-eligible beneficiaries and divided them into sex subgroups. Patients receiving LAAO were matched 1:1 to those receiving anticoagulation alone through propensity score matching. The risks of mortality, stroke or systemic embolism, and bleeding were compared between matched groups with adjustment for potential confounding characteristics in Cox proportional hazards models. RESULTS: Among women, 4085 LAAO recipients were matched 1:1 to those receiving anticoagulation; among men, 5378 LAAO recipients were similarly matched. LAAO was associated with a significant reduction in the risk of mortality for women and men (hazard ratio [HR], 0.509 [95% CI, 0.447-0.580]; and HR, 0.541 [95% CI, 0.487-0.601], respectively; P<0.0001), with a similar finding for stroke or systemic embolism (HR, 0.655 [95% CI, 0.555-0.772]; and HR, 0.649 [95% CI, 0.552-0.762], respectively; P<0.0001). Bleeding risk was significantly greater in LAAO recipients early after implantation but lower after the 6-week periprocedural period for women and men (HR, 0.772 [95% CI, 0.676-0.882]; and HR, 0.881 [95% CI, 0.784-0.989], respectively; P<0.05). CONCLUSIONS: In a real-world population of older Medicare beneficiaries with AF, compared with anticoagulation, LAAO was associated with a reduction in the risk of death, stroke, and long-term bleeding among women and men. These findings should be incorporated into shared decision-making with patients considering strategies for reduction in AF-related stroke.

A Review of the Safety and Efficacy of Apixaban in Patients With Severe Renal Impairment.

Background Apixaban is a direct-acting oral anticoagulant (DOAC) used to treat or prevent thromboembolic events. Renal impairment limits DOAC use. Studies supporting Food and Drug Administration (FDA)-approval for apixaban did not include patients with a creatinine clearance < 25 mL/min. Consequently, limited guidance for use in end-stage renal disease (ESRD) exists in the package insert. An in-depth literature search reveals substantial evidence supporting the safety and effectiveness of apixaban in ESRD. Clinicians must have access to this evidence so that patients in need of apixaban therapy are appropriately managed. Objective To provide an up-to-date review of literature surrounding the safety and effectiveness of apixaban in patients with ESRD. Data Sources A PubMed search of research studies published through November 2021 was performed using a combination of the following terms: apixaban, severe renal impairment, end-stage renal disease, DOACs, safety, effectiveness, atrial fibrillation, anticoagulation. Study Selection/Data Extraction Relevant original research, review articles, and guidance recommendations were assessed for the use of apixaban in patients with ESRD. References from the above literature were also evaluated. Articles were selected for inclusion based on relevance to the topic, detailed methods, and complete results. Data Synthesis Numerous studies exist supporting the safety and effectiveness of apixaban in patients with ESRD who may or may not be on dialysis. Conclusion Multiple studies suggest that apixaban is possibly associated with a lower prevalence of bleeding and thromboembolic events compared with warfarin therapy in patients with ESRD and can be safely initiated in those within this sub-group who require anticoagulation with a DOAC. Clinicians should monitor for signs of bleeding throughout the duration of therapy.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Chronic Liver Disease: A Nationwide Cohort Study.

BACKGROUND: The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear. METHODS: We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders. RESULTS: Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46-0.90]) or apixaban (HR, 0.40 [95% CI, 0.19-0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47-1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91-3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58-0.82]), apixaban (HR, 0.60 [95% CI, 0.46-0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62-1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18-2.14]). CONCLUSIONS: Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.

Integrated Machine Learning Decision Tree Model for Risk Evaluation in Patients with Non-Valvular Atrial Fibrillation When Taking Different Doses of Dabigatran.

The new generation of nonvitamin K antagonists are broadly applied for stroke prevention due to their notable efficacy and safety. Our study aimed to develop a suggestive utilization of dabigatran through an integrated machine learning (ML) decision-tree model. Participants taking different doses of dabigatran in the Randomized Evaluation of Long-Term Anticoagulant Therapy trial were included in our analysis and defined as the 110 mg and 150 mg groups. The proposed scheme integrated ML methods, namely naive Bayes, random forest (RF), classification and regression tree (CART), and extreme gradient boosting (XGBoost), which were used to identify the essential variables for predicting vascular events in the 110 mg group and bleeding in the 150 mg group. RF (0.764 for 110 mg; 0.747 for 150 mg) and XGBoost (0.708 for 110 mg; 0.761 for 150 mg) had better area under the receiver operating characteristic curve (AUC) values than logistic regression (benchmark model; 0.683 for 110 mg; 0.739 for 150 mg). We then selected the top ten important variables as internal nodes of the CART decision tree. The two best CART models with ten important variables output tree-shaped rules for predicting vascular events in the 110 mg group and bleeding in the 150 mg group. Our model can be used to provide more visualized and interpretable suggestive rules to clinicians managing NVAF patients who are taking dabigatran.

Sex-stratified differences in early antithrombotic treatment response in patients presenting with ST-segment elevation myocardial infarction.

BACKGROUND: The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. METHODS: The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. RESULTS: Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P = .04). CONCLUSIONS: In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation.

Thromboprophylaxis in Patients With Fontan Circulation.

BACKGROUND: The optimal strategy for thromboprophylaxis in patients with a Fontan circulation is unknown. OBJECTIVES: The aim of this study was to compare the efficacy and safety of aspirin, warfarin, and nonvitamin K oral anticoagulants (NOACs) in a network meta-analysis. METHODS: Relevant studies published by February 2022 were included. The primary efficacy outcome was thromboembolic events; major bleeding was a secondary safety outcome. Frequentist network meta-analyses were conducted to estimate the incidence rate ratios (IRRs) of both outcomes. Ranking of treatments was performed based on probability (P) score. RESULTS: A total of 21 studies were included (26,546 patient-years). When compared with no thromboprophylaxis, NOAC (IRR: 0.11; 95% CI: 0.03-0.40), warfarin (IRR: 0.23; 95% CI: 0.14-0.37), and aspirin (IRR: 0.24; 95% CI: 0.15-0.39) were all associated with significantly lower rates of thromboembolic events. However, the network meta-analysis revealed no significant differences in the rates of major bleeding (NOAC: IRR: 1.45 [95% CI: 0.28-7.43]; warfarin: IRR: 1.38 [95% CI: 0.41-4.69]; and aspirin: IRR: 0.72 [95% CI: 0.20-2.58]). Rankings, which simultaneously analyze competing interventions, suggested that NOACs have the highest P score to prevent thromboembolic events (P score 0.921), followed by warfarin (P score 0.582), aspirin (P score 0.498), and no thromboprophylaxis (P score 0.001). Aspirin tended to have the most favorable overall profile. CONCLUSIONS: Aspirin, warfarin, and NOAC are associated with lower risk of thromboembolic events. Recognizing the limited number of patients and heterogeneity of studies using NOACs, the results support the safety and efficacy of NOACs in patients with a Fontan circulation.

Risk of venous thromboembolism and bleeding after major surgery for ovarian cancer: standard in-hospital versus extended duration of thromboprophylaxis.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in patients with ovarian cancer after major surgery. Based on limited data, international guidelines recommend extended thromboprophylaxis for up to 28 days. OBJECTIVES: To assess the incidence of VTE and bleeding within 30 days following major surgery in patients with ovarian cancer and to evaluate the association between VTE and thromboprophylaxis duration. METHODS: This was a single-center, retrospective, "before-after" cohort study in patients with ovarian cancer undergoing major surgery. Before July 2019, the local protocol mandated a standard course of thromboprophylaxis during hospital stay only. From July 2019 onward, patients received extended thromboprophylaxis for 28 days. The cumulative incidences of VTE and major bleeding within 30 days after surgery were estimated using the Kaplan-Meier method, with 95% confidence intervals (CIs). Cox regression analysis was performed to evaluate the association between thromboprophylaxis duration and VTE incidence. RESULTS: Between January 2018 and December 2020, 250 women were included, of which 118 (47.2%) received extended and 132 (52.8%) standard thromboprophylaxis. During follow-up, 12 patients developed VTE (cumulative incidence, 4.8%; 95% CI, 2.1-7.4) and 2 major bleeding (cumulative incidence 0.8%; 95% CI, 0.0-1.9). Compared with standard thromboprophylaxis, VTE incidence was numerically lower with extended duration of thromboprophylaxis (5/118 [4.2%] vs 7/132 [5.3%]) but not significantly different (hazard ratio, 0.80; 95% CI, 0.25-2.52). The risk of major bleeding was similar in both groups (1/118 [0.8%] vs 1/132 [0.8%]; hazard ratio, 1.12; 95% CI, 0.07-17.89). CONCLUSIONS: The cumulative VTE incidence in patients with ovarian cancer following major surgery was considerable. Extended thromboprophylaxis was safe and associated with a numerically lower risk of VTE but not significantly different.

Incidence, Predictors, and Outcomes of Major Bleeding Among Patients Hospitalized With Acute Heart Failure.

Acute heart failure (AHF) is a common etiology of hospitalization and is associated with morbidity, including bleeding. In this study, the authors sought to assess the incidence, types, and associates of major bleeding in patients hospitalized with AHF. The National Inpatient Sample from October 2015 to December 2018 was used to identify patients with AHF. The incidence of common bleeding etiologies, and patient demographics, co-morbidities, associated acute cardiac diagnoses, and invasive procedures, were identified. The multivariable logistic regression was used to identify predictors of bleeding and the association of bleeding episodes with inpatient mortality. During the study period, 1,106,634 patients were admitted with a primary diagnosis of AHF, of whom 58,955 (5.3%) had an episode of bleeding. Common bleeding sources were gastrointestinal (25.7%), hematuria (24%), respiratory (23.6%), and procedure-related bleeding (2.5%). Major bleeding was more common in patients with AHF with preserved ejection fraction (odds ratio 1.14, confidence interval 1.12 to 1.16, p <0.001) versus AHF with reduced ejection fraction and in men (odds ratio 1.3, confidence interval 1.29 to 1.31, p <0.001). Major bleeding was associated with higher mortality (7.0% vs 2.4%, p <0.001), longer length of stay (7 vs 4 days, p <0.001), and higher inpatient costs ($49,658 vs $27,636, p <0.001). In conclusion, major bleeding occurs in 5.3% of patients hospitalized with AHF and is associated with higher inpatient mortality and costs and longer length of stay.

Estimation of adverse events associated with P2Y12 receptor inhibitors stratified by academic research consortium for high bleeding risk criteria in acute coronary syndrome.

BACKGROUND: The usefulness of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in the selection of P2Y12 receptor inhibitors for acute coronary syndrome is unknown. This study investigated whether the selection of antiplatelet agents according to the ARC-HBR criteria could improve clinical outcomes. METHODS: This multicenter retrospective study included 1261 patients with acute coronary syndrome who received dual antiplatelet therapy, namely clopidogrel (75 mg, n = 529) or prasugrel (3.75 mg, n = 732) in addition to aspirin. The primary endpoint was net adverse clinical events (NACE) after hospital admission, including ischemic (death, myocardial infarction, ischemic stroke) and bleeding events (Bleeding Academic Research Consortium 3 or 5). Secondary outcomes were ischemic and bleeding events. For each patient, the observation period was defined as the duration of dual antiplatelet therapy after admission. RESULTS: During the observation period (average: 313 days), the rate of NACE was lower in the prasugrel group than the clopidogrel group (20.6% vs. 12.6%, respectively, P < 0.01). In patients who satisfied or did not satisfy the ARC-HBR criteria, prasugrel was associated with a 3.7% and 2.1% lower incidence of NACE, respectively, versus clopidogrel. Ischemic and bleeding events were less frequent in the prasugrel group than the clopidogrel group (11.5% vs. 7.9%, respectively, P = 0.03; 10.6% vs. 5.2%, respectively, P < 0.01). The estimated incidence models for NACE suggested that the difference between clopidogrel and prasugrel was greater in patients who satisfied the ARC-HBR criteria than in those who did not. CONCLUSIONS: Prasugrel is preferable to clopidogrel regardless of the ARC-HBR.

Modified percutaneous coronary intervention-derived risk models (PARIS and CREDO-Kyoto integer scoring systems) applied to Japanese transcatheter aortic valve replacement patients.

OBJECTIVE: Postprocedural ischaemic and bleeding risks after transcatheter aortic valve replacement (TAVR) remain a major concern. Nevertheless, no reliable risk models incorporating both possibilities are currently available. We aimed to assess the accuracy of percutaneous coronary intervention (PCI)-derived models and the performance of a recalibrated model that included variables more applicable to TAVR. METHODS: This study included 26 869 patients who had been enrolled in a national registry. Ischaemic events were defined as myocardial infarction, stroke, transient ischaemic attack or peripheral embolism at 1 year. Bleeding events were defined as any bleeding based on the Valve Academic Research Consortium-2 consensus document at 1 year. Patterns of Non-adherence to Anti-Platelet Regimen in Stented Patients (PARIS) and Coronary Revascularisation Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) integer scoring systems were tested. The models were recalibrated by applying new variables using the Fine and Gray method. RESULTS: The 1-year cumulative incidences for ischaemic and bleeding events were 2.7% and 3.1%. Patients with high PARIS and CREDO-Kyoto risk scores had higher incidences of both ischaemic (3.3% vs 2.4% vs 2.4%, p<0.001 and 2.8% vs 2.0% vs 0.8%, p<0.001) and bleeding events (3.3% vs 2.5% vs 0.8%, p<0.001 and 3.7% vs 3.0% vs 2.4%, p<0.001) when compared with intermediate and low-risk patients. The receiver operating characteristic area under the curves for these models were 0.53, 0.58, 0.56 and 0.55, respectively. After the models were recalibrated to incorporate variables more applicable to TAVR, the performance of ischaemic and bleeding models modestly improved (0.58 and 0.61, respectively). CONCLUSIONS: The PCI-derived models demonstrated modest accuracy but was inadequate for risk stratification of TAVR patients at 1-year follow-up. TRIAL REGISTRATION NUMBER: 3395.

Long-Term Outcomes and Duration of Dual Antiplatelet Therapy After Coronary Intervention With Second-Generation Drug-Eluting Stents: The Veterans Affairs Extended DAPT Study.

Background Recent guidelines on dual antiplatelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) balance the subsequent risks of major bleeding with ischemic events. Although generally favoring shorter DAPT duration with second-generation drug-eluting stents, the effects on long-term outcomes in the wider population are uncertain. Methods and Results We tracked all patients having PCI with second-generation drug-eluting stents in the Veterans Affairs Healthcare System between 2006 and 2016 for death, myocardial infarction, stroke, and major bleeding up to 13 years. We compared these outcomes with 4 DAPT durations of 1 to 5, 6 to 9, 10 to 12, and 13 to 18 months after the index PCI using hazard ratios (HRs) and 95% CIs from Cox proportional hazards models adjusted by inverse probability weighting. A total of 40 882 subjects with PCI were followed up for a median of 4.3 (25%-75%: 2.4-6.5) years. DAPT discontinuation was rare early after PCI (5.8% at 1-5 months and 6.3% at 6-9 months) but increased (19% and 44%) >9 months. The risk of cardiovascular and noncardiovascular death was higher (HR, 2.03-3.41) with DAPT discontinuation <9 months, likely reflecting premature cessation from factors related to early death. DAPT discontinuation after 9 months following PCI was associated with lower risks of death (HR, 0.93 [95% CI, 0.88-0.99]), cardiac death (HR, 0.79 [95% CI, 0.70-0.90]), myocardial infarction (HR, 0.75 [95% CI, 0.69-0.82]), and major bleeding (HR, 0.82 [95% CI, 0.74-0.91]). Results were similar with an index PCI for an acute coronary syndrome. Conclusions Stopping DAPT after 9 months is associated with lower long-term risks of adverse ischemic and bleeding events and supports recent guidelines of shorter duration DAPT after PCI with second-generation drug-eluting stents.

Heart-Brain Team Approach of Acute Myocardial Infarction Complicating Acute Stroke: Characteristics of Guideline-Recommended Coronary Revascularization and Antithrombotic Therapy and Cardiovascular and Bleeding Outcomes.

Background Acute myocardial infarction (AMI) infrequently occurs after acute stroke. The Heart-brain team approach has a potential to appropriately manage this poststroke cardiovascular complication. However, clinical outcomes of AMI complicating acute stroke (AMI-CAS) with the heart-brain team approach have not been characterized. The current study investigated cardiovascular outcomes in patients with AMI-CAS managed by a heart-brain team. Methods and Results We retrospectively analyzed 2390 patients with AMI at our institute (January 1, 2007-September 30, 2020). AMI-CAS was defined as the occurrence of AMI within 14 days after acute stroke. Major adverse cerebral/cardiovascular events (cardiac-cause death, nonfatal myocardial infarction, and nonfatal stroke) and major bleeding events were compared in subjects with  AMI-CAS and those without acute stroke. AMI-CAS was identified in 1.6% of the subjects. Most AMI-CASs (37/39=94.9%) presented ischemic stroke. Median duration of AMI from the onset of acute stroke was 2 days. Patients with AMI-CAS less frequently received primary percutaneous coronary intervention (43.6% versus 84.7%; P<0.001) and dual-antiplatelet therapy (38.5% versus 85.7%; P<0.001), and 33.3% of them did not receive any antithrombotic agents (versus 1.3%; P<0.001). During the observational period (median, 2.4 years [interquartile range, 1.1-4.4 years]), patients with AMI-CAS exhibited a greater likelihood of experiencing major adverse cerebral/cardiovascular events (hazard ratio [HR], 3.47 [95% CI, 1.99-6.05]; P<0.001) and major bleeding events (HR, 3.30 [95% CI, 1.34-8.10]; P=0.009). These relationships still existed even after adjusting for clinical characteristics and medication use (major adverse cerebral/cardiovascular event: HR, 1.87 [95% CI, 1.02-3.42]; P=0.04; major bleeding: HR, 2.67 [95% CI, 1.03-6.93]; P=0.04). Conclusions Under the heart-brain team approach, AMI-CAS was still a challenging disease, reflected by less adoption of primary percutaneous coronary intervention and antithrombotic therapies, with substantially elevated cardiovascular and major bleeding risks. Our findings underscore the need for a further refined approach to mitigate their ischemic/bleeding risks.

Risk of bleeding after ground-level falls in elderly patients with atrial fibrillation and warfarin therapy.

OBJECTIVES: The aim of this study was to investigate bleeding risk in patients treated with VKAs after ground-level falls, considering the type and severity of bleeding. METHODS: The study was designed as a retrospective cohort study and included a total of 204 elderly patients aged > 65 years treated for AF continuously with warfarin for more than 3 years. Data were obtained from hospital registries in Bratislava, Slovakia. A 5-year assessment of death/survival was performed to determine mortality. RESULTS: There was no statistically significant difference in severe bleeding (2.13 % with falls vs 2.55 % without, p = 1) and 5-year mortality (45 % and 38 % respectively, p = 0.3987) based on the presence of falls. Multivariate analysis, after adjustment for age, CHA2DS2VASc, HASBLED, stroke history, labile INR and number of falls showed that only HASBLED score was a statistically significant contributor (CI: 1.0245 - 1.0919, p = 0.0007) to severe bleeding. There was statistically significant difference in severe bleeding (18 % vs 0 %, p = 0.0132) between patients suffering from spontaneous and bleeding after falls and also when comparing individual bleeding episodes (12 % vs 1 %, p < 0.0001). There was no statistically significant difference in 5-year mortality between the two groups (43 % vs 42 % respectively, p = 0.3931). CONCLUSIONS: Our results show that occurrence of falls in AF patients treated with VKAs have no significant impact on the incidence of severe bleeding and 5-year mortality and that spontaneous bleeding was associated with a significantly higher risk of severe bleeding compared to bleeding after falling (Tab. 4, Ref. 30).

Risk of bleeding with factor Xa inhibitors versus unfractionated heparin in patients with acute kidney injury.

STUDY OBJECTIVE: To compare bleeding and thromboembolic events in patients receiving therapeutic doses of apixaban or rivaroxaban versus unfractionated heparin (UFH) in patients with acute kidney injury (AKI). DESIGN: Single-center, retrospective, observational study. SETTING: Ascension St. John Hospital in Detroit, Michigan. PATIENTS: Hospitalized adult patients who received therapeutic doses of factor Xa inhibitors (n = 250) or UFH (n = 250) for at least 24 h in the setting of AKI. MEASUREMENTS AND MAIN RESULTS: After adjusting for confounding factors, patients who received a factor Xa inhibitor experienced a lower risk of composite major and clinically relevant nonmajor bleeding (CRNMB) events compared with UFH (OR: 0.57, 95% CI: 0.34-0.94; p = 0.03). There was a significantly decreased risk of CRNMB events in the factor Xa inhibitor group (OR: 0.55, 95% CI: 0.33-0.91, p = 0.02); however, no significant differences in major bleeding or venous thromboembolism (VTE) were noted. CONCLUSIONS: Our results suggest that it may be preferable to continue patients in AKI on factor Xa inhibitors versus transitioning to UFH due to the lower risk of bleeding events.

Impact of Achieving Blood Pressure Targets and High Time in Therapeutic Range on Clinical Outcomes in Patients With Atrial Fibrillation Adherent to the Atrial Fibrillation Better Care Pathway: A Report From the COOL-AF Registry.

Background We aimed to determine the effect of integrating Atrial Fibrillation Better Care pathway compliance in relation to achievement of systolic blood pressure (SBP) targets and good control of time in therapeutic range (TTR) on clinical outcomes in patients with atrial fibrillation. Methods and Results We prospectively enrolled patients with nonvalvular atrial fibrillation  from 27 hospitals in Thailand. All clinical outcomes were recorded. Main outcomes were the composite of all-cause death or ischemic stroke/systemic embolism (SSE), as well as secondary outcomes of all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure. An SBP of 120 to 140 mm Hg was considered good blood pressure control. Target TTR was a TTR ≥65%. A total of 3405 patients were studied (mean age 67.8 years, 41.8% female). Full ABC pathway compliance was evident in 42.7%. For blood pressure control, 41.9% had SBP within target, whereas 35.9% of those on warfarin had TTR within target. The incidence rates of all-cause death/SSE, all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure were 5.29, 4.21, 1.51, 2.25, 0.78, and 2.84 per 100 person-years respectively. Adjusted hazard ratios and 95% CI of Atrial Fibrillation Better Care pathway compliance for all-cause death/SSE, all-cause death, and heart failure were 0.76 (0.62-0.94), 0.79 (0.62-0.99), and 0.69 (0.51-0.94), respectively, compared with noncompliance. Patients with Atrial Fibrillation Better Care compliance and SBP within target had a better outcome or TTR within target had better outcomes. Conclusions In COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Level in Patients With Non-Valvular Atrial Fibrillation in Thailand), a multicenter nationwide prospective cohort of patients with atrial fibrillation, achieving SBP within target and TTR ≥ 65% has added value to Atrial Fibrillation Better Care pathway compliance in the reduction of adverse clinical outcomes in patients with atrial fibrillation.