BACKGROUND:The ONCO PE (Optimal Duration of Anticoagulation Therapy for Low-Risk Pulmonary Embolism Patients With Cancer) trial demonstrated the superiority of 18-month compared with 6-month rivaroxaban treatment for cancer-associated low-risk pulmonary embolism in reducing recurrent venous thromboembolism. However, it was uncertain whether the results could be applicable to patients with different performance status (PS) scores, which evaluate the physical condition of patients with cancer undergoing anticancer treatment. METHODS:In this post hoc subgroup analysis of the ONCO PE trial, we compared the 18-month and 6-month rivaroxaban treatment groups in 2 subgroups: the low PS score (no restricted physical activity: PS=0; n=79) and high PS score (restricted physical activity: PS ≥1; n=99) subgroups. The primary end point was recurrent venous thromboembolism, and the major secondary end point was major bleeding. RESULTS:The rate of recurrent venous thromboembolism was lower in the 18-month rivaroxaban group than in the 6-month rivaroxaban group, significantly among the low PS score subgroup (2.7% versus 19.0%, P=0.049) and numerically among the high PS score subgroup without statistical significance (7.7% versus 19.1%, P=0.10). The rate of major bleeding was not different between the 2 groups among the low PS score subgroup (2.7% versus 7.1%, P=0.39), while it was numerically higher in the 18-month rivaroxaban group than in the 6-month rivaroxaban group among the high PS score subgroup, without statistical significance (11.5% versus 4.3%, P=0.20). CONCLUSIONS:Extended anticoagulation therapy for patients with cancer-associated low-risk pulmonary embolism might have a potential benefit in reducing thrombotic risk irrespective of PS score, whereas there might be some concerns on an increased risk of major bleeding in patients with a high PS score. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04724460.

Background: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk. Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events. Conclusions: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.

Background Anticoagulants are prescribed less frequently in older patients with atrial fibrillation (AF) because of concerns regarding bleeding risk, despite their high thromboembolism risk. Frailty assessed using the Clinical Frailty Scale (CFS) provides incremental risk stratification for mortality and bleeding after left atrial appendage closure (LAAC); however, its clinical implications remain unclear. Objective To evaluate the impact of frailty, assessed using the CFS, on clinical outcomes and postprocedural antithrombotic management following LAAC. Methods The OCEAN-LAAC registry included 1,409 patients who underwent LAAC. Patients were stratified by CFS into groups 1–3 and 4–8. The primary outcome was all-cause mortality at 1 year. Secondary outcomes included non-procedural major bleeding, ischemic stroke, device-related thrombi, and peri-procedural complications. Results Frailty (CFS 4–8) was present in 32.9% of patients. At 1 year, frail patients had higher mortality rates than nonfrail patients (10.3% vs 3.0%). After multivariable adjustment, frailty was independently associated with mortality (hazard ratio [HR] 3.23, 95% confidence interval [CI], 1.92–5.46). Frailty was also associated with non-procedural major bleeding in the competing risk analysis (subdistribution HR 2.13, 95% CI 1.14–3.96). Despite more frequent de-escalation of antithrombotic therapy in frail patients, rates of ischemic stroke and device-related thrombosis did not differ significantly across frailty groups. Conclusion Frailty assessed using the CFS identifies patients at increased risk of mortality and bleeding after LAAC and may provide incremental risk stratification to guide individualized postprocedural management. Clinical trial registration number OCEAN-LAAC registry (UMIN ID: UMIN000038498)

Background: The ONCO DVT study demonstrated potential benefits of extended edoxaban treatment in patients with isolated distal deep vein thrombosis in terms of thrombotic risk. However, the risk-benefit balance in patients with anemia remains unclear. Methods and Results: This prespecified subgroup analysis included 601 patients, divided into anemia (n=402) and no-anemia (n=199) groups. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death. Anemia was defined as hemoglobin <12g/dL for women and <13g/dL for men. In the anemia subgroup, the primary endpoint occurred in 3 (1.5%) and 17 (8.4%) patients in the 12-and 3-month edoxaban treatment groups, respectively (odds ratio [OR] 0.17; 95% confidence interval [CI] 0.05-0.58), compared with 0 and 5 (4.9%) patients, respectively, in the no-anemia subgroup (P interaction=0.997). Major bleeding occurred in 26 (13.1%) and 17 (8.4%) patients with anemia in the 12-and 3-month edoxaban treatment groups, respectively (OR 1.64; 95% CI 0.86-3.14), compared with 2 (2.1%) and 5 (4.9%) patients without anemia (OR 0.67; 95% CI 0.26-1.73; P interaction=0.13). Conclusions: Regardless of the presence of anemia, edoxaban treatment for 12 months was superior to treatment for 3 months in reducing thrombotic events, whereas the risk of major bleeding did not differ significantly between the 2 treatment groups.

Background: Previous randomized clinical trials did not support a benefit of screening for occult cancer after diagnosis of venous thromboembolism (VTE), although screening may be of potential benefit for selected high-risk patients. Methods and Results: The COMMAND VTE Registry-2 enrolled consecutive patients with acute symptomatic VTE between 2015 and 2020 from 31 centers across Japan. The 3,706 patients in the registry without known active cancer at the time of VTE diagnosis were divided into 2 groups: those with (n=250) and without (n=3,456) newly diagnosed cancer during the follow-up period. The cumulative incidence of newly diagnosed cancer was 1.5% at 30 days, 3.7% at 1 year, and 7.0% at 3 years. The multivariable Cox proportional hazard model demonstrated that older age (hazard ratio [HR] 1.02 per 1 year increase; 95% confidence interval [CI] 1.01-1.03; P<0.001), a history of cancer (HR 3.57; 95% CI 2.73-4.64; P<0.001), autoimmune disorders (HR 1.48; 95% CI 1.06-2.02; P=0.02), a history of major bleeding (HR 1.64; 95% CI 1.04-2.48; P=0.04), and the absence of transient provoking risk factors for VTE (HR 1.44; 95% CI 1.08-1.92; P=0.01) were independently associated with newly diagnosed cancer. Conclusions: The incidence of newly diagnosed cancer after VTE diagnosis was 3.7% at 1 year, and several independent risk factors for newly diagnosed cancer after VTE diagnosis were identified.

Very high acute pacing thresholds (VHPT) during AVEIR-AR atrial leadless pacemaker (ALP) implantation often prompt device repositioning, although excessive manipulation may increase procedural risk. To evaluate the safety and early electrical performance of ALP release despite VHPT using a current-of-injury (COI)-guided strategy. We retrospectively analyzed 28 consecutive patients who underwent AVEIR-AR ALP implantation at two centers in Japan and compared procedural safety and short-term electrical performance between patients with normal PTs (NPT <5.5 V at 0.4 ms) and those with VHPT (≥5.5 V at 0.4 ms). In the VHPT group, ALP device release was permitted when pre-screw COI was adequate (≥1 mV). The mean age was 85±6 years, body weight was 54±8 kg, and 11 patients were female. Single-site pre-mapping successful implantation was achieved in 36

The ONCO DVT study demonstrated the benefit of extended anticoagulation therapy with edoxaban in patients with cancer-associated isolated distal deep vein thrombosis (DVT). However, it remains unclear whether these results can be applied regardless of the number of thrombosed venous segments. In this post-hoc subgroup analysis of the ONCO DVT study, 601 patients were stratified into the single-site (N=268) and multiple-sites (N=333) DVT subgroups based on the number of thrombosed venous segments at diagnosis. We compared 12-month and 3-month edoxaban treatment groups in each subgroup for the primary endpoint of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death and the major secondary endpoint of major bleeding at 12 months. The cumulative 12-month incidence of the primary endpoint was significantly lower in the 12-month edoxaban group than in the 3-month edoxaban group both in the single-site (0.8

Abstract:The ONCO PE trial showed that 18-month rivaroxaban was superior to 6-month rivaroxaban for preventing recurrent venous thromboembolism (VTE) in patients with cancer-associated low-risk pulmonary embolism (PE). However, the influence of concomitant deep vein thrombosis (DVT) on this benefit was unclear. The current post-hoc subgroup analysis of the ONCO PE trial categorized patients into DVT subgroup (N = 104) and no DVT subgroup (N = 74) based on the presence or absence of a concomitant DVT at PE diagnosis. We compared the primary endpoint of 18-month recurrent VTE and the major secondary endpoint of 18-month major bleeding between the 18- and 6-month rivaroxaban groups in the DVT and no DVT subgroups. The cumulative 18-month incidence of recurrent VTE in the 18-month rivaroxaban group was numerically lower compared with that in the 6-month rivaroxaban group in the DVT subgroup (11.5 vs. 20.9%, log-rank p = 0.25) and was significantly lower in the no DVT subgroup (0.0 vs. 24.2%, log-rank p = 0.006), without significant interaction between treatment durations and concomitant DVT (Pinteraction = 0.99). There were no significant differences in the cumulative 18-month incidence of major bleeding between the 18- and 6-month rivaroxaban groups in both the DVT (4.6 vs. 5.8%, log-rank p = 0.70) and no DVT (13.4 vs. 5.8%, log-rank p = 0.29) subgroups, without significant interaction (Pinteraction = 0.34). The current exploratory analysis showed that extended rivaroxaban treatment might have a potential benefit for patients with cancer-associated low-risk PE in preventing recurrent VTE, irrespective of concomitant DVT status, without a significantly increased risk of major bleeding.

Background: Data on the association of weekend vs. weekday diagnosis with clinical outcomes of venous thromboembolism (VTE) in the direct oral anticoagulant (DOAC) era are limited. Methods and Results: The COMMAND VTE Registry-2 is a multicenter registry that enrolled 5,197 consecutive acute symptomatic VTE patients from 31 centers in Japan between January 2015 and August 2020. Baseline characteristics, anticoagulation strategies, and 30-day outcomes were compared between patients diagnosed on weekends (n=537; 10.3%) and those diagnosed on weekdays (n=4,660, 89.7%). Compared with patients diagnosed on weekdays, those diagnosed on weekends more frequently presented with pulmonary embolism (PE; 74.7% vs. 51.2%; P<0.001) and more often received thrombolysis and cardiopulmonary support. The cumulative 30-day incidence of all-cause death in PE patients was significantly higher in patients diagnosed on weekends than in those diagnosed on weekdays (7.5% vs. 4.1%; P=0.003), but the difference was not significant after multivariable adjustment (hazard ratio 1.51; 95% confidence interval [CI] 0.99-2.30; P=0.056). The 30-day risk of major bleeding was significantly higher in weekend PE patients after multivariable adjustment (hazard ratio 1.79; 95% CI 1.11-2.88; P=0.02). Conclusions: VTE patients diagnosed on weekends presented more often with PE and with greater severity. Although the higher crude 30-day mortality in weekend PE patients was attenuated after adjustment, a weekend diagnosis remained associated with higher 30-day major bleeding risk.

The ONCO PE trial demonstrated the superiority of 18-month compared with 6-month rivaroxaban treatment for cancer-associated acute low-risk pulmonary embolism (PE) in reducing recurrent venous thromboembolism (VTE). However, it was uncertain whether the results could be applicable to patients in different stages of chemotherapy exposure.In this prespecified subgroup analysis of the ONCO PE trial, patients were classified into chemotherapy (n = 107) and nonchemotherapy (n = 71) subgroups based on the status of chemotherapy exposure at the PE diagnosis. We compared the primary endpoint of recurrent VTE and the major secondary endpoint of major bleeding between the 18- and 6-month rivaroxaban treatment groups in each subgroup.The cumulative 18-month incidence rate of recurrent VTE was numerically lower in the 18-month rivaroxaban group than in the 6-month rivaroxaban group among both the chemotherapy (6.6% vs. 20.8%, log-rank p = 0.06) and nonchemotherapy subgroups (6.6% vs. 23.4%, log-rank p = 0.09) without a significant interaction between chemotherapy exposure and treatment duration (p-interaction = 0.94). There was no significant difference in the cumulative 18-month incidence of major bleeding between the 18- and 6-month rivaroxaban groups among either the chemotherapy (9.7% vs. 4.1%, log-rank p = 0.29) or nonchemotherapy subgroup (6.2% vs. 8.0%, log-rank p = 0.73) without a significant interaction between chemotherapy exposure and treatment duration (p-interaction = 0.36).Extended anticoagulation therapy for patients with cancer-associated acute low-risk PE might have a potential benefit in reducing thrombotic risk irrespective of the status of chemotherapy exposure without a significantly increased risk of major bleeding.

Background Patients with cancer-associated venous thromboembolism (VTE) are at a high risk of major bleeding during anticoagulant therapy, emphasizing the need for bleeding risk assessment in the era of direct oral anticoagulants (DOACs). However, few bleeding risk scores have been specifically developed and validated for this population. Objectives The aim of this study was to develop and validate a novel bleeding risk score (ONCO-DOAC BLEED score) for patients with cancer-associated VTE receiving DOAC therapy. Methods We derived the bleeding risk prediction score using 1,166 patients with cancer-associated VTE treated with DOAC therapy from the COMMAND VTE (Contemporary Management and Outcomes in Patients with Venous Thromboembolism) Registry-2 and externally validated its performance in an independent cohort from the ONCO deep vein thrombosis and ONCO pulmonary embolism studies. Results Over a median follow-up of 163 days, 127 patients (10.9%) experienced major bleeding. In multivariable analysis, a history of major bleeding, chronic kidney disease, nonsteroidal anti-inflammatory drug use, distant metastatic cancer, terminal cancer, upper gastrointestinal cancer, pancreatic cancer, and uterine cancer were independently associated with major bleeding. Based on these risk factors, the ONCO-DOAC BLEED score was constructed. This score demonstrated moderate discrimination for major bleeding in the derivation cohort (Harrell's C-index 0.68; Uno's C-index 0.67) and validation cohort (Harrell's C-index 0.62; Uno's C-index 0.63), with higher discrimination in the derivation cohort and comparable performance in the validation cohort compared with the VTE-BLEED, RIETE, CAT-BLEED, and Perform scores. Conclusions The ONCO-DOAC BLEED score provides clinically relevant stratification of major bleeding risk in patients with cancer-associated VTE receiving DOAC therapy and may support individualized therapeutic decision-making in routine practice. (Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study [ONCO DVT]; NCT03895502 and Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer [ONCO PE]; NCT04724460)

BACKGROUND:Low body weight (BW) is reportedly associated with an increased risk of bleeding and mortality in venous thromboembolism (VTE). However, there are limited data on the impact of low BW on clinical outcomes among patients with cancer-associated VTE in the direct oral anticoagulants (DOACs) era. METHODS AND RESULTS:We analyzed 1,484 patients with symptomatic VTE and active cancer from the COMMAND VTE Registry-2, and divided the cohort into low (≤60 kg) and non-low (>60 kg) BW groups (n=969 and 515, respectively). The cumulative 3-year incidence of major bleeding was significantly higher in the low than non-low BW group (13.1% vs. 10.2%; Gray's P=0.04). However, after adjustment, the risk of major bleeding in the low BW was no longer significantly different to that in the non-low BW group (hazard ratio [HR] 1.36; 95% confidence interval [CI] 0.96-1.92). The cumulative 3-year incidence of recurrent VTE did not differ significantly between the low and non-low groups (5.2% vs. 5.4%, respectively; Gray's P=0.46; adjusted HR 0.71; 95% CI 0.42-1.18). The cumulative 3-year incidence of all-cause death was significantly higher in the low than non-low BW group (65.0% vs. 50.8%; log-rank P<0.001; adjusted HR 1.47; 95% CI 1.25-1.73). CONCLUSIONS:Low BW in cancer-associated VTE was not associated with major bleeding or recurrent VTE, but was associated with all-cause death, possibly reflecting cancer-related prognostic factors.

Cancer-associated isolated distal deep vein thrombosis (IDDVT) is a common complication in patients with cancer. The Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients with Cancer study revealed the superiority of 12- over 3-month edoxaban treatment with respect to thrombotic risk. However, it remains unclear whether D-dimer levels during anticoagulation influence the efficacy of extended anticoagulation. In this post hoc subgroup analysis, we stratified 519 patients into the low D-dimer (<1.0 μg/mL) (n = 308) and high D-dimer (≥1.0 μg/mL) (n = 211) subgroups based on D-dimer levels at 3 months. The cumulative incidence of a composite of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death was lower in the 12-month edoxaban group than in the 3-month edoxaban group in both the low D-dimer (0.8% vs 5.6%; P = .02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.66) and high D-dimer (0.9% vs 10.2%; P = .01; OR, 0.11; 95% CI, 0.01-0.62) subgroups without interaction. Furthermore, there was no significant difference in the cumulative incidence of major bleeding between the 12- and 3-month groups in both the low D-dimer (3.6% vs 1.8%; P = .64; OR, 1.96; 95% CI, 0.47-9.67) and high D-dimer (18.3% vs 14.6%; P = .29; OR, 1.27; 95% CI, 0.60-2.75) subgroups without interaction. In conclusion, a 12-month edoxaban treatment for cancer-associated IDDVT was superior to a 3-month treatment in reducing thrombotic events, irrespective of D-dimer levels after 3 months of anticoagulation therapy. There was no significant increased risk of major bleeding in the 12-month edoxaban group relative to the 3-month edoxaban group regardless of the D-dimer levels at 3 months. This trial was registered at www.clinicaltrials.gov as #NCT03895502.

The ONCO PE trial showed the potential benefit of extended anticoagulation therapy with rivaroxaban in patients with cancer and acute low-risk pulmonary embolism (PE) of the simplified version of the Pulmonary Embolism Severity Index (sPESI) score of 1 with respect to recurrent venous thromboembolism (VTE) events. However, it also suggested a potential signal for an increased risk of bleeding with an 18-month compared to 6-month rivaroxaban treatment duration. This post-hoc analysis aimed to compare the net clinical benefit (NCB) of an 18-month compared to 6-month rivaroxaban treatment duration. The ONCO PE trial was a multicenter, open-label, randomized controlled trial, in which patients with cancer and acute low-risk of the sPESI score of 1 were randomly assigned (1:1) to the 18-month or 6-month rivaroxaban treatment group. Firstly, we assessed the net adverse clinical events (NACE), which were defined as a simple combination of the thrombotic and bleeding events, in each treatment group. We defined NACE-1 as a composite endpoint of recurrent VTE or major bleeding at 18 months. In addition, to assess the broader spectrum of events, we defined NACE-2 as a composite endpoint of recurrent VTE or all clinically relevant bleeding at 18 months. Secondly, we assessed the NCB of 18-month compared to 6-month rivaroxaban, which was defined as the sum of the differences in the incidence of thrombotic and bleeding events between the 2 treatment groups. We set the bleeding weight as 1.0 in the base case analyses. The NCB-1 and NCB-2 corresponded to NACE-1 and NACE-2, respectively. We calculated the NCB with the bleeding weights set at 0.5 and 2. Of the 178 eligible patients, 89 were in the 18-month group and 89 in the 6-month group. With a bleeding weight of 1.0, the incidence rates of NACE-1 were 10.8 (95% CI, 6.0–19.5) events per 100 person-years in the 18-month group and 18.6 (95% CI, 11.9–29.2) in the 6-month group (incidence rate ratio [IRR], 0.61; 95% CI, 0.29–1.29). The NCB-1 was 9.0% (95% CI, -1.9% to 19.9%). The incidence rates of NACE-2 were 25.1 (95% CI, 16.7–37.7) events per 100 person-years in the 18-month group and 34.5 (95% CI, 24.3–49.1) in the 6-month group (IRR, 0.79; 95% CI, 0.46–1.35). The NCB-2 was 9.0% (95% CI, -4.5% to 22.4%). As the bleeding weights increased from 0.5 to 2, the NCB-1 became attenuated from 10.7% (95% CI, 0.7% to 20.7%) to 5.6% (95% CI, -6.7% to 18.0%) (Figure A), and the NCB-2 also became attenuated from 10.7% (95% CI, -1.0% to 22.3%) to 5.6% (95% CI, -9.0% to 20.3%) (Figure B). The NCB of the 18-month compared to 6-month rivaroxaban treatment duration was not significant, although the 18-month treatment had a numerically lower incidence of NACE than the 6-month treatment.

BACKGROUND:In patients with atrial fibrillation-related ischemic stroke despite oral anticoagulation (AFIDA), left atrial appendage closure (LAAC) may be an additional strategy to prevent further stroke events. METHODS AND RESULTS:AFIDA was defined as ischemic stroke occurring despite ≥3 weeks of oral anticoagulation (OAC). We evaluated patients with AFIDA treated either with OAC alone (n=141; further divided into aggressive OAC [n=73] and conventional OAC [n=68] subgroups) or with additional LAAC (+LAAC; n=95; further divided into continued OAC [n=44] and discontinued OAC within 1 year after LAAC [n=51] subgroups). Patients in the +LAAC group were younger, had higher HAS-BLED scores, and lower HELT-E2S2scores. Three-year cumulative incidence rates of ischemic stroke and major bleeding were comparable between the OAC alone and +LAAC groups (15.2% vs. 14.5% [log-rank P=0.75] and 23.4% vs. 5.3% [log-rank P=0.38], respectively), whereas those of fatal or disabling stroke and fatal bleeding were lower in the +LAAC than OAC alone group (3.4% vs. 14.7% [log-rank P=0.06] and 0% vs. 6.0% [log-rank P=0.03], respectively). Results of propensity score-matched and subgroup analyses were largely consistent with those of the main analysis. Notably, fatal bleeding occurred only in patients switched to aggressive OAC. CONCLUSIONS:LAAC may potentially prevent fatal or disabling stroke and fatal bleeding in patients with AFIDA. These hypothesis-generating findings support the need for randomized controlled trials.

Background: The direct-acting oral anticoagulant (DOAC) score has been validated for assessing the bleeding risk in patients with atrial fibrillation (AF). However, data on DOAC scores in patients undergoing percutaneous left atrial appendage closure (LAAC) is limited. This study aimed to evaluate the predictive impact of the DOAC score on clinical events following LAAC and compare it with that of the HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio [INR], Elderly [age >65 years], Drugs and alcohol concomitantly) score. Methods: In this prospective, multicenter, observational study, patients with nonvalvular AF (NVAF) undergoing LAAC were categorized by the DOAC score into higher (HBR) and lower bleeding risk groups. The primary endpoints of all-cause death, stroke, and bleeding were evaluated at 3 months and 1 year. Results: Among 1464 patients (mean age 77.1 years; 67.6% male), the HBR group (923 patients) had a lower body mass index, more frequent comorbidities, and higher risk profiles for bleeding and stroke. The device, technical, and procedural success rates were high and similar between groups. At 1 year, the primary endpoint was higher in the HBR group (17.6% vs 12.4%, P = 0.01), influenced by differences in bleeding events (10.9% vs 7.6%, P = 0.045). The DOAC score showed superior predictive value for the primary endpoint compared with the HAS-BLED score. Conclusions: The DOAC score is a reliable predictor of composite outcomes, including death, stroke, and bleeding, in patients undergoing LAAC, demonstrating superior utility compared with the HAS-BLED score. This scoring system may improve risk stratification and patient management in daily clinical practice.

BACKGROUND:The optimal duration of anticoagulation therapy for patients with cancer and acute low-risk pulmonary embolism (PE) is clinically relevant, but evidence is lacking. Prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS:In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 32 institutions in Japan, we randomly assigned patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, in a 1:1 ratio, to receive either an 18-month or a 6-month rivaroxaban treatment. The primary end point was recurrent venous thromboembolism (VTE) at 18 months. The major secondary end point was major bleeding at 18 months according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that an 18-month treatment was superior to a 6-month treatment in terms of the primary end point. RESULTS:From February 2021 to March 2023, 179 patients were randomized, and after the exclusion of one patient who withdrew consent, 178 were included in the intention-to-treat population: 89 patients in the 18-month rivaroxaban group and 89 in the 6-month rivaroxaban group. The mean age was 65.7 years; 47% of the patients were men, and 12% had symptoms of PE at baseline. The primary end point of recurrent VTE occurred in 5 of the 89 patients (5.6%) in the 18-month rivaroxaban group and in 17 of the 89 (19.1%) in the 6-month rivaroxaban group (odds ratio, 0.25 [95% CI, 0.09-0.72]; P=0.01). Among 22 recurrent VTE, 5 patients presented with a symptomatic recurrent VTE; recurrent PE occurred in 11 patients, including 2 with main and 4 with lobar PEs; and recurrent deep vein thrombosis was seen in 11 patients, including 3 with proximal deep vein thromboses. The major secondary end point of major bleeding occurred in 7 of the 89 patients (7.8%) in the 18-month rivaroxaban group and in 5 of the 89 patients (5.6%) in the 6-month rivaroxaban group (odds ratio, 1.43 [95% CI, 0.44-4.70]; P=0.55). CONCLUSIONS:In patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, the 18-month rivaroxaban treatment was superior to the 6-month rivaroxaban treatment with respect to recurrent VTE events. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04724460.