Risk Burden of Cancer in Patients Treated With Abbreviated Dual Antiplatelet Therapy After PCI: Analysis of Multicenter Controlled High-Bleeding Risk Trials.

BACKGROUND: Oncological patients with coronary artery disease face an elevated risk of hemorrhagic and ischemic events following percutaneous coronary intervention. Despite medical guidelines recommending minimal dual antiplatelet therapy (DAPT) duration for patients with cancer, dedicated data on abbreviated DAPT in this population is lacking. This study aims to evaluate the occurrence of ischemic and hemorrhagic events in patients with cancer compared with other high-bleeding risk individuals. METHODS: Patient-level data from 4 high-bleeding risk coronary drug-eluting stent studies (ONYX One, LEADERS FREE, LEADERS FREE II, and SENIOR trials) treated with short DAPT were analyzed. The comparison focused on patients with high-bleeding risk with and without cancer, assessing 1-year rates of net adverse clinical events (all-cause death, myocardial infarction, stroke, revascularization, and Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and major adverse clinical events (all-cause death, myocardial infarction, stroke). RESULTS: A total of 5232 patients were included, of whom 574 individuals had cancer, and 4658 were at high-bleeding risk without previous cancer. Despite being younger with fewer risk factors, patients with cancer had higher net adverse clinical event (HR, 1.25; P=0.01) and major adverse clinical event (HR, 1.26; P=0.02), primarily driven by all-cause mortality and major bleeding (BARC 3-5), but not myocardial infarction, stroke, stent thrombosis, or repeat revascularization. Cancer was an independent predictor of net adverse clinical event (P=0.005), major adverse clinical event (P=0.01), and major bleeding (P=0.03). CONCLUSIONS: The present work is the first report on abbreviated DAPT dedicated to patients with cancer. Cancer is a major marker of adverse outcomes and these events had high lethality. Despite short DAPT, patients with cancer experienced higher rates of major bleeding compared with patients without cancer with high-bleeding risk, which occurred mainly after DAPT discontinuation. These findings reinforce the need for a more detailed and individualized stratification of those patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03344653, NCT01623180, NCT02843633, NCT0284.

Incidence and risk factors for pulmonary hemorrhage after percutaneous CT-guided pulmonary nodule biopsy: an observational study.

To evaluate the current incidence of pulmonary hemorrhage and the potential factors contributing to its increased risk after percutaneous CT-guided pulmonary nodule biopsy and to summarize the technical recommendations for its treatment. In this observational study, patient data were collected from ten medical centers from April 2021 to April 2022. The incidence of pulmonary hemorrhage was as follows: grade 0, 36.1% (214/593); grade 1, 36.8% (218/593); grade 2, 18.9% (112/593); grade 3, 3.5% (21/593); and grade 4, 4.7% (28/593). High-grade hemorrhage (HGH) occurred in 27.2% (161/593) of the patients. The use of preoperative breathing exercises (PBE, p =0.000), semiautomatic cutting needles (SCN, p = 0.004), immediate contrast enhancement (ICE, p =0.021), and the coaxial technique (CoT, p = 0.000) were found to be protective factors for HGH. A greater length of puncture (p =0.021), the presence of hilar nodules (p = 0.001), the presence of intermediate nodules (p = 0.026), a main pulmonary artery diameter (mPAD) larger than 29 mm (p = 0.015), and a small nodule size (p = 0.014) were risk factors for high-grade hemorrhage. The area under the curve (AUC) was 0.783. These findings contribute to a deeper understanding of the risks associated with percutaneous CT-guided pulmonary nodule biopsy and provide valuable insights for developing strategies to minimize pulmonary hemorrhage.

Development and Validation of Machine Learning Algorithms to Predict 1-Year Ischemic Stroke and Bleeding Events in Patients with Atrial Fibrillation and Cancer.

In this study, we leveraged machine learning (ML) approach to develop and validate new assessment tools for predicting stroke and bleeding among patients with atrial fibrillation (AFib) and cancer. We conducted a retrospective cohort study including patients who were newly diagnosed with AFib with a record of cancer from the 2012-2018 Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The ML algorithms were developed and validated separately for each outcome by fitting elastic net, random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), and neural network models with tenfold cross-validation (train:test = 7:3). We obtained area under the curve (AUC), sensitivity, specificity, and F2 score as performance metrics. Model calibration was assessed using Brier score. In sensitivity analysis, we resampled data using Synthetic Minority Oversampling Technique (SMOTE). Among 18,388 patients with AFib and cancer, 523 (2.84%) had ischemic stroke and 221 (1.20%) had major bleeding within one year after AFib diagnosis. In prediction of ischemic stroke, RF significantly outperformed other ML models [AUC (0.916, 95% CI 0.887-0.945), sensitivity 0.868, specificity 0.801, F2 score 0.375, Brier score = 0.035]. However, the performance of ML algorithms in prediction of major bleeding was low with highest AUC achieved by RF (0.623, 95% CI 0.554-0.692). RF models performed better than CHA2DS2-VASc and HAS-BLED scores. SMOTE did not improve the performance of the ML algorithms. Our study demonstrated a promising application of ML in stroke prediction among patients with AFib and cancer. This tool may be leveraged in assisting clinicians to identify patients at high risk of stroke and optimize treatment decisions.

Real-world experience of direct oral anticoagulant use in a single pediatric center.

BACKGROUND: Pediatric venous thromboembolism has increased by 130%-200%, specifically in hospitalized children, and direct oral anticoagulants (DOACs) offer several therapeutic advantages. METHODS: This study aims to evaluate the real-world epidemiological and outcome data from a retrospective review of pediatric patients treated with DOACs from January 1, 2013 to December 31, 2022. In this single-center, IRB-approved study, 65 patients were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted. RESULTS: Of the 65 patients, 37% were on apixaban, 61.5% were on rivaroxaban, and 1.5% were on dabigatran. Per the 2023 ISTH outcome definitions, one (2%) patient had a major bleeding episode, six (9%) had clinically relevant non-major bleeding, three (5%) patients had patient-important heavy menstrual bleeding (HMB), and one (1.5%) patient had minor bleeding. Seven (19%) of 37 postmenarchal patients had evidence of HMB. Six (9.2%) patients had recurrent venous thromboembolism while on a DOAC (one was on apixaban, and five were on rivaroxaban) and were transitioned to other forms of anticoagulation. CONCLUSION: Thus, bleeding rates after DOAC therapy are comparable to previous DOAC trials, as well as other anticoagulants in pediatrics. HMB is an important outcome measure and should continue to be investigated. This study reports a higher rate of recurrent thrombosis (9.2%) compared to other trials. However, this observation may be attributed to patients who had ongoing risk factors, as well as a longer duration of study follow-up. Additional multicentered outcome studies evaluating DOAC use in children are needed to determine long-term recurrence and HMB risks.

Risk of thrombosis, hemorrhage and leukemic transformation in patients with myeloproliferative neoplasms: A nationwide longitudinal cohort study.

INTRODUCTION: There are few large-scale, population-based studies detailing the risks of thrombosis, hemorrhage, leukemic transformation in patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). METHODS: We performed a nationwide longitudinal cohort study using the Korean National Health Insurance System (NHIS) database. MPN patients (n = 11,991) and their 1:4 age- and sex-matched controls (n = 47,964) were enrolled. The risk of thrombosis, hemorrhage, leukemic transformation was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors. RESULTS: During a median of 7.8 years of follow-up, 30.1 % of MPN patients (3614/11,991) and 19.0 % of the matched controls (9141/47,964) developed arterial thrombosis, 11.6 % of MPN patients (1397/11,991) and 6.4 % of the matched controls (3099/47,964) developed venous thrombosis and 18.7 % of MPN patients (2251/11,991) and 12.1 % of the matched controls (5836/47,964) developed hemorrhage. 4.9 % of MPN patients (597/11,991) and 0.1 % of matched controls (50/47,964) developed leukemia. The overall risk of developing thrombosis, hemorrhage, leukemic transformation was higher in MPN patients (adjusted hazard ratio [aHR] 1.695, 95 % confidence interval [CI]: 1.629-1.765 for arterial thrombosis, aHR 1.963, 95 % CI: 1.838-2.096 for venous thrombosis, and aHR 1.714, 95 % CI: 1.630-1.802 for hemorrhage) than in the controls. Patients with MPNs had a 10-year cumulative incidence of leukemic transformation of 6.2 %. CONCLUSION: The patients with MPNs have a higher risk of thrombosis, hemorrhage, and leukemic transformation than matched controls. Strategies are warranted to reduce the risk of thrombosis, hemorrhage, and leukemic transformation in MPN patients.

Treatment patterns and outcomes among adults with immune thrombocytopenia receiving pharmaceutical second-line therapies: a retrospective cohort study using administrative claims data.

OBJECTIVES: To describe and compare real-world treatment patterns and clinical outcomes among individuals with immune thrombocytopenia (ITP) receiving second-line therapies (rituximab, romiplostim, or eltrombopag). METHODS: A retrospective cohort study was conducted using a large administrative claims database (January 2013-May 2020) among continuously enrolled patients ≥18 years prescribed second-line ITP therapies. The index date was the date of the first claim of the study medications. Treatment patterns and outcomes were measured during the 12-month follow-up period. Inverse probability of treatment weighting (IPTW) was used to balance covariates across treatment groups. Multivariable logistic regression was used to compare treatment patterns and bleeding risk outcomes. RESULTS: A total of 695 patients were included (rituximab, N = 285; romiplostim, N = 212; eltrombopag, N = 198). After IPTW, all baseline covariates were balanced. Compared to eltrombopag, patients in the rituximab cohort were 57% more likely to receive other ITP therapies (systematic corticosteroids or third-line therapies) during the follow-up period (odds ratio [OR] = 1.571, p = .030). There was no significant difference in the odds of receiving a different second-line therapy or experiencing a bleeding-related episode among three groups (p > .050). Patients in the romiplostim cohort were 69% more likely to receive rescue therapy compared to those in the rituximab cohort (OR = 1.688, p = .025). CONCLUSION: Patients with ITP receiving rituximab were more likely to need other ITP therapies but did not experience higher risk of bleeding compared to those receiving eltrombopag or romiplostim. Benefits, risks, cost-effectiveness, and patient preference should all be considered in optimizing second-line therapy for ITP.

Comparison of Outcomes in Patients Requiring Mechanical Circulatory Support Who Received Cangrelor in Addition to Anticoagulation Versus Anticoagulation Alone.

OBJECTIVES: To evaluate the safety of cangrelor administered concurrently with heparin or bivalirudin in patients on mechanical circulatory support. DESIGN: A single-center, retrospective cohort study of adult patients consecutively admitted between January 2016 and October 2020. SETTING: A tertiary medical center. PARTICIPANTS: Adult patients admitted to the cardiovascular intensive care unit put on mechanical circulatory support for acute myocardial infarction (AMI) or non-AMI indications. Patients who received cangrelor underwent percutaneous coronary intervention with stenting during the index event or within the last year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of major bleeding, defined by the Extracorporeal Life Support Organization criteria, in patients with mechanical circulatory support receiving cangrelor plus anticoagulation with heparin or bivalirudin with or without aspirin versus patients who did not receive cangrelor. Sixty-eight patients were included in the study. Twenty-nine patients received cangrelor, and 39 did not. Cangrelor was not associated with an increase in major bleeding; however, the CI was wide (adjusted hazard ratio 1.93, 95% CI 0.61-6.11; p = 0.262). CONCLUSIONS: Patients receiving cangrelor did not appear to be at higher risk of major bleeding compared to patients not receiving cangrelor. Larger trials should be conducted to better evaluate the safety of cangrelor in patients with mechanical circulatory support.

Risk and adverse clinical outcomes of thrombocytopenia among patients with solid tumors-a Danish population-based cohort study.

BACKGROUND: Knowledge about thrombocytopenia among patients with solid tumors is scarce. We examined the risk of thrombocytopenia among patients with solid tumors and its association with adverse outcomes. METHODS: Using Danish health registries, we identified all patients with incident solid tumors from 2015-2018 (n = 52,380) and a platelet count measurement within 2 weeks prior to or on their cancer diagnosis date. The risk of thrombocytopenia was categorized as grades 0 (any platelet count × 109/L): <150; 1: <100; 2: <75; 3: <50; 4: <25, and 5: <10. To study the outcomes, each patient with thrombocytopenia was matched with up to five cancer patients without thrombocytopenia by age, sex, cancer type, and stage. Cox regression was used to compute hazard ratios (HRs) of bleeding, transfusion, or death, adjusting for confounding factors. RESULTS: The 1-year risk of thrombocytopenia was 23%, increasing to 30% at 4 years. This risk was higher in patients receiving chemotherapy (43% at 1 year and 49% at 4 years). Overall, patients with thrombocytopenia had higher 30-days rates of bleeding (HR = 1.72 [95% confidence interval, CI: 1.41-2.11]). Thrombocytopenia was also associated with an increased rate of transfusion, and death, but some of the risk estimates were imprecise. CONCLUSIONS: The risk of thrombocytopenia was substantial among patients with solid tumors and associated with adverse outcomes.

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.

Vascular compactness of unruptured brain arteriovenous malformation predicts risk of hemorrhage after stereotactic radiosurgery.

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm3 versus 20-40 cm3 versus > 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV-V compared with grade I-III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV-V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs.

Coronary events in elderly patients with non-valvular atrial fibrillation: a prespecified sub-analysis of the ANAFIE registry.

Real-world data on coronary events (CE) in elderly patients with atrial fibrillation (AF) are lacking in the direct oral anticoagulant era. This prespecified sub-analysis of the ANAFIE Registry, a prospective observational study in > 30,000 Japanese patients aged ≥ 75 years with non-valvular AF (NVAF), investigated CE incidence and risk factors. The incidence and risk factors for new-onset CE (a composite of myocardial infarction [MI] and cardiac intervention for coronary heart diseases other than MI), MI, and cardiac intervention for coronary heart diseases other than MI during the 2-year follow-up were assessed. Bleeding events in CE patients were also examined. Among 32,275 patients, the incidence rate per 100 patient-years was 0.48 (95% confidence interval (CI): 0.42-0.53) for CE during the 2-year follow-up, 0.20 (0.16-0.23) for MI, and 0.29 (0.25-0.33) for cardiac intervention for coronary heart diseases other than MI; that of stroke/systemic embolism was 1.62 (1.52-1.73). Patients with CE (n = 287) likely had lower creatinine clearance (CrCL) and higher CHADS2 and HAS-BLED scores than patients without CE (n = 31,988). Significant risk factors associated with new-onset CE were male sex, systolic blood pressure of ≥ 130 mmHg, diabetes mellitus (glycated hemoglobin ≥ 6.0%), CE history, antiplatelet agent use, and CrCL < 50 mL/min. Major bleeding incidence was significantly higher in patients with new-onset CE vs without CE (odds ratio [95% CI], 3.35 [2.06-5.43]). In elderly patients with NVAF, CE incidence was lower than stroke/systemic embolism incidence. New-onset CE (vs no CE) was associated with a higher incidence of major bleeding.Trial registration: UMIN000024006.

Pneumothorax and pulmonary hemorrhage after C-arm cone-beam computed tomography-guided percutaneous transthoracic lung biopsy: incidence, clinical significance, and correlation.

OBJECTIVE: This study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters. METHODS: A retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH. RESULTS: PTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH. CONCLUSIONS: CBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.

Clinical and molecular determinants of bleeding-related adverse outcomes in high-grade glioma.

PURPOSE: Cancer is an independent risk factor for the development of venous thromboembolism (VTE). However, patients with high-grade glioma (HGG) including glioblastoma (GBM) are at a particularly high risk of VTE with an incidence up to 20-30% per year. Patients are often placed on anticoagulation if they are found to have VTE. However, patients with primary brain tumors such as HGG are at increased risk for intracerebral hemorrhage (ICH) even without the administration of anticoagulation. The combination of risk factors for ICH with anticoagulation and HGG complicates decision-making. Currently it is not known which of the direct oral anticoagulants (DOACs) are safest for patients with HGG in terms of adverse bleeding-related outcomes such as ICH. Furthermore, a deeper understanding of the clinical and molecular determinants of bleeding-related adverse outcomes in HGG is not fully characterized. METHODS: In this retrospective study, we identified and gathered data on 75 consecutive patients with pathology-confirmed HGG with hospital encounters at two academic medical center hospitals in Austin between July 1, 2017 and June 30, 2022. We compared clinical and treatment-related factors among cohorts who had received various forms of anticoagulation or no anticoagulation. RESULTS: Patients who were on rivaroxaban (3/7 (43%)) had a statistically significant association with more bleeding-related adverse events compared to those on apixaban (0/12 (0%)) or enoxaparin (0/5 (0%), p = 0.022) even though the groups were similar in characteristics including total time on the respective anticoagulation. Patients on anticoagulation vs those never on anticoagulation did not differ in terms of their studied demographic and clinical characteristics. Intriguingly, logistic regression analysis revealed that patients Astrocytoma, isocitrate dehydrogenase (IDH) mutant, grade 4 had a significant association with more adverse bleeding-related events even when controlling for other relevant factors (Odds Ratio compared to reference GBM: 49.4, 95% CI: 2.8, 2084.7; p = 0.013). CONCLUSION: In this study we found that the use of rivaroxaban was associated with more bleeding-related events compared to apixaban and enoxaparin in patients with high-grade glioma. In this study we also found that the diagnosis of astrocytoma, IDH mutant, grade 4 was associated with more bleeding events. However, this is based on a small study and there is a need for larger studies to further evaluate these results.

Transition of management strategies and long-term outcomes in cancer-associated venous thromboembolism from the warfarin era to the direct oral anticoagulant era.

BACKGROUND: There have been still limited data on the transition of management strategies and clinical outcomes after introduction of direct oral anticoagulant (DOAC) for cancer-associated venous thromboembolism (VTE) in the real-world clinical practice. METHODS: Using the 2 series of multicenter COMMAND VTE registries in Japan enrolling consecutive patients with acute symptomatic VTE, we compared 695 patients with cancer-associated VTE in the Registry-1 of the warfarin era and 1507 patients in the Registry-2 of the DOAC era. RESULTS: Regarding oral anticoagulation therapy, 576 patients (82.9 %) in the Registry-1 received warfarin, whereas 1119 patients (79.6 %) in the Registry-2 received DOACs. The cumulative 3-year incidence of discontinuation of anticoagulation was not significantly different between the 2 registries (56.7 % vs. 62.7 %, P = 0.11). The cumulative 5-year incidence of recurrent VTE was significantly lower in the Registry-2 than in the Registry-1 (17.7 % vs. 10.1 %, P < 0.001). The cumulative 5-year incidence of major bleeding was significantly lower in the Registry-2 than in the Registry-1 (26.6 % vs. 20.4 %, P = 0.045). The proportion of gastrointestinal bleeding numerically increased from the Registry-1 to the Registry-2 (46.7 % and 49.5 %), whereas that of intracranial bleeding numerically decreased from the Registry-1 to the Registry-2 (17.1 % and 14.1 %). CONCLUSIONS: In the current historical comparison of cancer-associated VTE between the 2 large real-world registries, there was a striking change in the treatment strategies with decreased risks of recurrent VTE and major bleeding in the DOAC era compared with those in the warfarin era, while there seemed to be unmet needs of DOAC-related gastrointestinal bleeding. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm UNIQUE IDENTIFIER: UMIN000044816.

Obesity may be a risk factor for transbronchial lung cryobiopsy-related adverse events in Japanese patients with interstitial lung disease.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is known to be associated with a high incidence of adverse events. However, few studies have investigated the correlation between obesity and the risk of TBLC-related adverse events, especially in Asians, who are known to have characteristic differences in height and weight as compared to individuals of other ethnicities. METHODS: We retrospectively assessed 102 Japanese patients who underwent TBLC for the diagnosis of interstitial lung disease to evaluate the correlation between patient characteristics and the occurrence of TBLC-related adverse events (hemorrhage, pneumothorax, and acute exacerbation of interstitial lung disease). RESULTS: TBLC-related adverse events occurred in 19 patients (18.6 %), with hemorrhage being the most common adverse event (in 14 patients, 13.7 %). There was no correlation between age, sex, or pulmonary function test results and the occurrence of adverse events. The body mass index (BMI) cut-off predicting the occurrence of all adverse events was 26.6 kg/m2 (sensitivity of 0.389 and specificity of 0.852), and that predicting the occurrence of adverse events of hemorrhage was 26.8 kg/m2 (sensitivity of 0.462 and specificity of 0.907). Among patients with a BMI >26.8 kg/m2, adverse events of hemorrhage occurred in 37.5 % of cases, which was higher than among those with a BMI <26.8 kg/m2. CONCLUSIONS: Obesity is a risk factor for the incidence of TBLC-related adverse events, particularly adverse events of hemorrhage, in Japanese patients. The BMI cut-off values that predicted an increased frequency of TBLC-related adverse events and hemorrhage specifically were 26.6 and 26.8 kg/m2, respectively.

De-escalation of Antiplatelet Therapy After Percutaneous Coronary Intervention in East Asian Patients With Acute Coronary Syndrome.

PURPOSE: East Asian individuals have a lower risk of thromboembolic events while potentially carrying a higher risk of bleeding events compared with non-Asian individuals. The aim of the present analysis was to investigate the effectiveness and safety of the de-escalation of antiplatelet therapy compared with standard dual antiplatelet therapy (DAPT) in East Asian patients undergoing percutaneous coronary intervention (PCI). METHODS: Randomized controlled trials comparing de-escalation with DAPT in patients with acute coronary syndrome (ACS) were retrieved from electronic databases from their inception until March 2022. Outcomes included major adverse cardiovascular events (MACE), ischemic events, major bleeding, minor bleeding, and any bleeding. Subgroup analyses based on treatment strategy were conducted. Statistical analysis was performed by using Review Manager version 5.4. FINDINGS: Eight randomized controlled trials from 539 potentially relevant publications with a total of 15,744 East Asian patients were included. Pooled data from these studies found a significantly lower MACE (0.82; 95% CI, 0.69-0.98) and major bleeding event (0.62; 95% CI, 0.46-0.82) in de-escalation than standard-DAPT without heterogeneity. Subgroup analysis was divided into DAPT followed by P2Y12 inhibitor monotherapy and a reducing dose of P2Y12 inhibitors. DAPT followed by P2Y12 inhibitor monotherapy had a 48% lower incidence of major bleeding events than standard DAPT (0.52; 95% CI, 0.27-1.00); there was no significant difference in major bleeding (0.99; 95% CI, 0.55-1.76) between the reducing dose of P2Y12 inhibitors and standard DAPT. IMPLICATIONS: De-escalation is a promising and potentially optimal antiplatelet therapy for patients from East Asia with PCI. DAPT followed by P2Y12 inhibitor monotherapy might be a safer and equally effective approach compared with standard DAPT in East Asian patients with PCI. PROSPERO identifier: CRD42022319983.

Acute pulmonary embolism and cancer: findings from the COPE study.

BACKGROUND: Patients with acute venous thromboembolism associated with cancer have an increased risk of recurrences and bleeding in the long term. RESEARCH QUESTION: To describe the clinical features and short-term course of patients with acute pulmonary embolism (PE) and active cancer, previous cancer or no cancer. STUDY DESIGN AND METHODS: Patients with acute PE included in COPE-prospective, multicentre study of adult patients with acute, symptomatic, objectively diagnosed PE-were classified as having active cancer, previous cancer, or no cancer. RESULTS: Overall, 832 patients had active cancer, 464 with previous cancer and 3660 patients had no cancer at the time of acute PE. The most prevalent primary sites of active cancer were urogenital (23.0%), gastrointestinal (21.0%), and lung (19.8%), with a high prevalence of metastatic disease (57.6%) and ongoing anticancer treatment (16.2%). At discharge, a direct oral anticoagulant was used in 43.1%, 78.8%, and 82.0% of patients with active cancer, previous cancer, and no cancer, respectively. Rates of death in-hospital and at 30 days were higher in patients with active cancer compared to patients with previous cancer and no cancer (7.9% vs. 4.3% vs. 2.2% and 13.8% vs. 5.2% vs. 2.6%, respectively). Rates of major bleeding were 4.8%, 2.6%, and 2.4%, respectively. Among patients with active cancer, lung or metastatic cancer were independent predictors of death; brain, hematological or gastrointestinal cancer had the highest risk of major bleeding. INTERPRETATION: Among patients with acute PE, those with active cancer have high risks for death or major bleeding within 30 days. These risks vary based on primary site of cancer. CLINICAL TRIAL REGISTRATION: clinicaltrial.gov identifier: NCT03631810.

Safety and efficacy of catheter ablation for atrial fibrillation in cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Cancer survivors are at increased risk for atrial fibrillation (AF). However, data on the efficacy and safety of catheter ablation (CA) in this population remain limited. Therefore, we aimed to perform a systematic review and meta-analysis comparing outcomes after CA for AF in patients with versus without prior or active cancer. METHODS: We systematically searched PubMed, Cochrane Library, and Embase from inception to April 2023 for studies comparing the safety and efficacy of CA for AF in cancer survivors. Outcomes of interest were bleeding events, late AF recurrence, and need for repeat ablation. Statistical analyses were performed using Review Manager 5.4.1. We pooled odds ratios (OR) with 95% confidence intervals (CI) for binary endpoints. RESULTS: We included 5 retrospective cohort studies comprising 998 patients, of whom 41.4% had a history of cancer. Cancer survivors were at significantly higher risk of clinically relevant bleeding (OR 2.17; 95% CI 1.17-4.0; p=0.01) as compared with those without cancer. The efficacy of CA for AF was similar between groups. Late AF recurrence at 12 months was not significantly different between patients with vs. without a history of cancer (OR 1.29; 95% CI 0.78-2.13; p=0.32). Similar findings were observed in the outcome of repeat ablations (OR 0.71; 95% CI 0.37-1.37; p=0.31). CONCLUSIONS: These findings suggest that cancer survivors have an increased risk of bleeding after CA for AF relative to patients without cancer, with no significant difference in the efficacy of CA for maintenance of sinus rhythm between groups. STUDY REGISTRATION: This systematic review is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023394538.

Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry.

BACKGROUND: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. METHODS: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. RESULTS: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep-vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). CONCLUSIONS: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

The clinical outcomes of different doses of rivaroxaban in patients with isolated distal deep vein thrombosis.

OBJECTIVE: Isolated distal deep vein thrombosis (IDDVT) is defined as thrombosis involving the infrapopliteal veins. The optimal anticoagulant therapy of IDDVT remains controversial. This study aimed to assess whether reduced dose of rivaroxaban was suitable in patients with IDDVT. METHODS: Consecutive patients with acute IDDVT were identified by reviewing the venous thromboembolism (VTE) registry databases. Outcomes including VTE recurrence, major bleeding, clinically relevant non-major (CRNM) bleeding, and death. Patients were followed until the first occurrence of any outcomes or the study end date (December 31, 2018). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. RESULTS: A total of 1246 patients were divided into low-dose (10 or 15 mg/day; n = 716) and standard-dose (20 mg/day; n = 530) groups. The incidences of VTE recurrence, major bleeding, CRNM bleeding, and death between the two groups were 9.64% vs 5.66%, 1.68% vs 3.02%, 4.61% vs 8.68%, and 13.83% vs 10.75%, respectively. After the inverse probability of treatment weighting, HRs for standard-dose vs low-dose of VTE recurrence, major bleeding, CRNM bleeding, and death were 0.54 (95% CI, 0.35-0.84), 1.71 (95% CI, 0.80-3.67), 2.28 (95% CI, 1.40-3.74), and 1.30 (95% CI, 0.91-1.86), respectively. For the subgroup analysis, the interaction with anticoagulation duration and treatment was evident for VTE recurrence (P for interaction = .002), but not for major bleeding. Patients with residual vein thrombosis were associated with an increased risk of VTE recurrence (HR, 1.95; 95% CI, 1.29-2.95). The interaction between risk factors and residual vein thrombosis was evident for VTE recurrence (P for interaction = .085). CONCLUSIONS: Standard-dose rivaroxaban reduced the risk of VTE recurrence without increasing the risk of major bleeding in patients with IDDVT. Anticoagulant therapy for >1.5 months should be preferred over shorter durations. Residual vein thrombosis should be assessed as a predictor of recurrence in patients with IDDVT, especially for patients with non-transient factors.