Rates Of Clinically Relevant Nonmajor Bleeding Research Articles

Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial.

Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

Safety and Effectiveness of Direct Oral Anticoagulants for the Treatment of Gastrointestinal Cancer-Associated Venous Thromboembolism.

Patients with gastrointestinal cancer (GICA) are at high risk for venous thromboembolism (VTE). Data from randomized clinical trials in cancer-associated VTE suggest that direct oral anticoagulants (DOACs) conferred similar or superior efficacy but a heterogeneous safety profile in patients with GICA. We compared the safety and effectiveness of DOACs in patients with GICA and VTE at MD Anderson Cancer Center. This was a retrospective chart review of patients with GICA and VTE receiving treatment with DOACs for a minimum of 6 months. Primary outcomes were the proportion of patients experiencing major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE. Secondary outcomes were time to bleeding and recurrent VTE. A cohort of 433 patients with GICA who were prescribed apixaban (n = 300), or rivaroxaban (n = 133) were included. MB occurred in 3.7% (95% confidence interval [CI] 2.1-5.9), CRNMB in 5.3% (95% CI 3.4-7.9), and recurrent VTE in 7.4% (95% CI 5.1-10.3). The cumulative incidence rates of CRNMB and recurrent VTE were not significantly different when comparing apixaban to rivaroxaban. Apixaban and rivaroxaban had a similar risk of recurrent VTE and bleeding and could be considered as anticoagulant options in selected patients with GICA and VTE.

Efficacy and safety of rivaroxaban for the treatment of PICC-related upper extremity deep vein thrombosis in cancer patients: a retrospective study

BackgroundThe optimal duration and choice of anticoagulant for the treatment of Peripherally inserted central catheters (PICC)-related upper extremity deep vein thrombosis (UEDVT) in cancer patients are still undetermined.ObjectivesThe aim of this study was to assess the efficacy and safety of rivaroxaban for the treatment of PICC-related UEDVT in cancer patients.MethodsWe conducted a retrospective cohort study including consecutive cancer patients for the management of acute symptomatic PICC-related UEDVT. The efficacy outcome of the study was the 180-day recurrence of any venous thromboembolism (VTE), while the safety outcome was the 180-day incidence of all bleeding events. The Kaplan‒Meier method was used to estimate the overall incidence. Hazard ratios (HRs) were obtained with a Cox proportional hazards model to estimate the risk of the outcome events.ResultsA total of 217 patients were included in the final analysis with a median age of 56 years old, 41.5% of whom had metastases. After the initial 3–5 days of nadroparin, patients received sequential anticoagulation, either with nadroparin (118 patients) or with rivaroxaban (99 patients). Four patients with recurrent VTE were observed (nadroparin, n = 2; rivaroxaban, n = 2). The 180-day cumulative VTE recurrence rates were 1.7% and 2.0% (p = 0.777) in patients receiving nadroparin and rivaroxaban, respectively. The overall bleeding rate at 180 days was 8.8%. Although no major bleeding events were observed, nineteen patients with clinically relevant nonmajor bleeding (CRNMB) were observed. The 180-day cumulative rate of CRNMB was 5.1% for nadroparin and 13.1% for rivaroxaban (HR = 3.303, 95% CI 1.149–9.497, p = 0.027).ConclusionOur study supported the efficacy of rivaroxaban for treating PICC-related UEDVT in cancer patients. However, data on anticoagulation therapy for PICC-related UEDVT presented with a low risk of VTE recurrence and a relatively high risk of CRNMB bleeding events. Considering the risk–benefit ratio, further well-designed trials are required to optimize the drug selection and duration for the treatment of PICC-related UEDVT in cancer patients.

Impact of Thrombocytopenia on Bleeding and Recurrent Thrombosis in Cancer Associated Thrombosis: A Post Hoc Analysis of Hokusai VTE Cancer Study

Background: Thrombosis and thrombocytopenia are both frequent complications in patients with active cancer. Thrombocytopenia can complicate decisions around anticoagulation in cancer associated thrombosis (CAT) but data to guide clinicians is limited. Much of the data on the safety and efficacy of anticoagulation in patients with CAT and thrombocytopenia have been retrospective, single-center, cohort studies. The benefit and risk of direct oral anticoagulants in cancer patients with acute venous thromboembolism (VTE) and thrombocytopenia is incompletely understood. The HOKUSAI VTE Cancer study was a randomized open-label, non-inferiority, phase III trial in CAT that compared dalteparin with edoxaban for at least 6 months. We conducted a post hoc analysis of this trial to investigate the impact of platelet count on bleeding and recurrent thrombosis. Methods: Patients with platelet counts less than 100,000/µL at specified time points (enrollment, day 31 or day 90) were compared with patients with platelet count > 100,000/µL on all three time points. The primary outcomes for these analyses was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis and survival. Cumulative incidences of bleeding and thrombosis outcomes were calculated with death as a competing risk. Results: A total of 1045 patients were included in the analyses. , The median age was 65 years and 52% were male. Most common malignancies included colorectal (16%), lung (15%), genitourinary (13%), breast (12%), and hematologic malignancies (11%). Of patients with solid cancers, 53% had metastatic disease and 30% recurrent disease at enrollment. Qualifying thrombotic events included pulmonary embolism for 63% and isolated deep vein thrombosis in 37%. Thrombocytopenia (<100,000/µL) was present in 101 patients (9.6%) of the total cohort. Only 14 patients had a platelet count <50,000/µL at any of the three time points. For the overall trial period the rates of major bleeding were significantly higher in patients with platelet count <100,000/µL (11.9% vs. 4.8%, HR 2.5 P=0.004). (Table 1) Rates of CRNMB were similarly higher in patients with platelet count <100,000/ µL (21.8% vs. 11.9%, HR 1.93, P=0.005), however there was no significant difference in rates of recurrent VTE (11.9% vs. 9.2%, HR 1.28 P=0.42) or overall mortality (37.6% vs. 38%, HR 0.98, P=0.90). Cumulative incidence of major bleeding at 180 days was higher 8.9% (95% CI 3.4-14.5%) in patients with platelet count <100,000/ µL compared to 3.9% (95% CI 2.7-5.2%) in those higher than 100,000/µL. (Figure 1) Conclusion: In this post hoc analysis of a randomized controlled study in CAT, thrombocytopenia (<100,000/µL) was associated with an increased risk of major bleeding by two-fold. No difference in the risk of recurrent thrombosis was detected. These data highlight the importance of recognizing even mild thrombocytopenia as an important risk factor for bleeding in patients being anticoagulated for CAT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban, Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism

ObjectiveTo compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE). Patients and MethodsConsecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB). ResultsIn the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37). ConclusionApixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer. Trial RegistrationClinicalTrials.gov identifier: NCT03504007.

Direct Oral Anticoagulants (DOACs) Vs. Low Molecular Weight Heparins (LMWH) for Venous Thromboembolism (VTE) in Patients with Primary Brain Tumors or Secondary Brain Metastases

Background: Management of venous thromboembolism (VTE) in patients with central nervous system (CNS) malignancies is challenging as there is an increased risk of recurrent VTE and intracranial hemorrhage (ICH). Low molecular weight heparins (LMWH) have historically been the standard of care for treatment of cancer-associated thrombosis (CAT). Current guidelines recommend direct oral anticoagulants (DOACs) for CAT treatment, but patients with CNS malignancies have limited representation in the supporting clinical trials. This multicenter, retrospective cohort study evaluated the safety and efficacy of DOACs compared to LMWH for CAT in patients with primary brain tumors or secondary brain metastases. Patients/Methods: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for CAT were evaluated. The primary outcome was the incidence of any bleeding event within a 6-month period following the initiation of anticoagulation. Secondary outcomes included incidence of recurrent VTE events, major bleeding, clinically relevant non-major bleeding (CRNMB), and minor bleeding, within a 6-month period following the initiation of anticoagulation. Patients were excluded if their indication for anticoagulation was stroke, non-cancer-associated VTE, or VTE prophylaxis, were on LMWH for one week or less while bridging to warfarin, or received a diagnosis of VTE at an outside hospital. All bleeding events were defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Primary and secondary outcomes were analyzed using Fisher's exact test for categorical variables and Wilcoxon rank-sum tests for non-parametric continuous variables. Results: Between January 1, 2012 to October 9, 2019, one-hundred eleven patients met inclusion criteria. Of the patients who met inclusion criteria, 26 (23.4%) patients had primary brain tumors and 85 (76.6%) patients had secondary brain metastases. Bleeding events occurred in 7 of 55 patients (12.7%) in the DOAC group compared to 13 of 56 (23.2%) patients in the LMWH group (RR 0.55, 95% CI 0.24-1.27). Recurrent VTE events occurred in 3 of 55 (5.5%) patients in the DOAC group compared to 3 of 56 (5.4%) patients in the LMWH group (RR 1.02, 95% CI 0.21-4.83). Major bleeding occurred in 3 of 55 (5.5%) patients in the DOAC group, compared to 4 of 56 (7.1%) patients in the LMWH group (RR 0.76, 95% CI 0.18-3.26). There were no differences in the rates of CRNMB and rates of minor bleeding between groups. Conclusion: In this multicenter retrospective cohort study, therapeutic anticoagulation with DOACs showed no significant difference in bleeding events or recurrent VTE events when compared to LMWH, in patients with primary brain tumors or secondary brain metastases. We conclude that DOACs may be potentially safe and efficacious for VTE treatment in patients with primary brain tumors or secondary brain metastases. As prescribing practices are expected to continue to shift towards DOACs, this study provides preliminary evidence of the safety of DOACs in this high-bleeding risk patient population. Disclosures No relevant conflicts of interest to declare.

Direct Oral Anticoagulants in Patients With Active Cancer: A Systematic Review and Meta-Analysis

BackgroundMany patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate. ObjectivesThis study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs). MethodsThis study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst). ResultsThis study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11). ConclusionsDOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies.

Perioperative interruption of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: A comparative analysis

BackgroundThere is a paucity of studies comparing postoperative thromboembolic and major bleeding complications following perioperative interruption of the direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). Objective/MethodsWe conducted a retrospective cohort study to compare postoperative thromboembolic and major bleeding outcomes following perioperative interruption of DOACs and VKAs in patients with atrial fibrillation. The primary efficacy and safety outcomes were the 30‐day postoperative rates of arterial thromboembolic events (ATEs) and major bleeding, respectively. The secondary outcomes included the 30‐day rates of clinically relevant nonmajor bleeding (CRNMB) and overall mortality. Thromboembolic, major bleeding, and mortality outcomes were independently adjudicated. Multivariable mixed‐effects logistic‐regression models were used to adjust for potential confounding variables between the DOAC and VKA cohorts. ResultsA total of 325 DOAC patients undergoing 351 procedures and 199 VKA patients undergoing 221 procedures were included. The 30‐day ATE rate was 0.57% (95% confidence interval [CI], 0.27‐0.8) in the DOAC cohort. There were no ATEs in the VKA cohort. The 30‐day rates of major bleeding were 0.57% (95% CI, 0.27‐0.8) and 3.62% (95% CI, 0‐7.3) in the DOAC and the VKA cohorts, respectively. There were significantly more postoperative major bleeding events in the VKA cohort. The 30‐day rate of CRNMB was 4.27% (95% CI, 4.15‐4.42) in the DOAC cohort and 4.52% (95% CI, 3.67‐5.38) in the VKA cohort. There were 2 deaths in the VKA cohort, one of which was deemed to be a fatal nonsurgical bleeding event. ConclusionsThe perioperative interruption of VKAs may be associated with higher postoperative major bleeding rates as compared to DOACs. Careful postoperative reinitiation and monitoring of VKA anticoagulation may be warranted following surgical procedures.

Thromboprophylaxis for Patients with Newly Diagnosed Vs. Recurrent Cancers: A Post-Hoc Analysis of the Avert Trial

Background: The risk of venous thromboembolism (VTE) is increased in cancer patients, which can result in significant increases in mortality, morbidity and healthcare expenditures. The recent AVERT trial (N Engl J Med 2019 Feb 21;380(8):711-719), showed that prophylactic apixaban lowered the rate of VTE when compared to placebo in cancer patients starting chemotherapy. However, the risk-benefit ratio of primary thromboprophylaxis in patients initiating chemotherapy for recurrent disease compared to those with newly diagnosed patients who are chemotherapy naïve is unknown. Methods: This is a post-hoc analysis of the AVERT trial. The AVERT trial assessed apixaban therapy vs. placebo for prophylaxis among patients with cancer who were intermediate-to-high risk for VTE (Khorana score ≥2; the Khorana score is ranged from 0 to 6 with higher scores reflecting an increased risk of VTE) and were initiating chemotherapy. It was a randomized, placebo-controlled, double-blind clinical trial. The primary efficacy outcome was VTE and the main safety outcomes were major bleeding episodes. Secondary outcome measures included clinically relevant non-major bleeding (CRNMB). The severity of major bleeding was stratified from category 1 to 4, with category 4 being the most severe type. We performed time-to-event analysis on the primary efficacy and main safety end-points in patients with recurrent and new diagnosed cancers. The hazard ratio (HR) for the outcomes were estimated using a Cox regression model controlling for age, gender, and center. Results: A total of 574 patients were randomized in the AVERT trial. 563 were included in the modified intention-to-treat analysis. 237 and 232 patients with newly diagnosed cancer were allocated to the apixaban and placebo groups, respectively. Similarly, 51 and 43 patients with recurrent cancer were allocated to the apixaban and placebo groups, respectively. Baseline demographics and clinical characteristics are depicted in Table 1A and Table 1B. In patients with newly diagnosed cancers, the use of apixaban was associated with a significantly lower risk of VTE (HR: 0.45; 95% CI: 0.27-0.76; p = 0.002) and a higher rate of major bleeding complications (HR: 2.10; 95% CI: 1.09-4.08; p = 0.028) but not of CRNMB (HR: 1.06; 95% CI: 0.61-1.82) (Table 2A). A majority of the major bleeding complications were of category 2. In patients with recurrent cancer, apixaban was associated with a significant lower rate of VTE (HR: 0.26; 95% CI: 0.13-0.53; p &amp;lt; 0.001) without an associated significant increased risk of major bleeding complication (HR: 1.82; 95% CI: 0.36-9.15; p = 0.466) but with a significant increase rate of CRNMB (HR: 2.78; 95% CI: 0.58-1.34; p = 0.006) (Table 2B). Major bleeding episodes were split evenly between severity category 1 and 2. Conclusion: The risk-benefit ratio of primary thromboprophylaxis with apixaban might differ between patients with recurrent or newly diagnosed cancers. Apixaban was associated with a lower rate of VTE compared to placebo in both groups. Patients with recurrent cancer initiating chemotherapy may potentially have a more favorable risk benefit profile, as shown through the HR and the prevalence of major bleeding episodes. However, more trials are required to confirm these findings to help tailor thromboprophylaxis in this patient population. (AVERT ClinicalTrials.gov number, NCT02048865.) Disclosures Wells: BMS/Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Sanofi: Honoraria; Daiichi Sankyo: Honoraria. Carrier:Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Servier: Honoraria; Bayer: Honoraria; Pfizer: Honoraria, Research Funding. OffLabel Disclosure: Apixaban can be used as postoperative prophylaxis of DVT/PE and for treatment of DVT/PE. This study will show whether the prophylactic effects of apixaban will be more effective when used with patients with recurrent cancer or patients with newly diagnosed cancer.

Periprocedural interruption of anticoagulation in patients with cancer‐associated venous thromboembolism: An analysis of thrombotic and bleeding outcomes

Unlabelled Box BackgroundPatients with cancer are at high risk for venous thromboembolic events. Venous thromboembolism (VTE) can lead to significant morbidity among patients with cancer, and is estimated to be one of the leading causes of death among cancer patients. Patients with cancer often require invasive procedures for biopsy or therapeutic purposes. There is a lack of data on postoperative outcomes following interruption of anticoagulation in this population. ObjectiveTo assess 30‐day postoperative thromboembolic and major bleeding complication rates following the perioperative interruption of anticoagulation in patients with cancer‐associated VTE. MethodsWe conducted a retrospective self‐controlled case series study with patients with cancer‐associated VTE undergoing perioperative interruption of anticoagulation at a dedicated tertiary‐care anticoagulation clinic for invasive procedures between January 2013 and March 2018. The primary efficacy and safety outcomes were the 30‐day postoperative rates of VTE and major bleeding, respectively. The secondary outcomes included the 30‐day rates of clinically relevant non‐major bleeding (CRNMB) and overall mortality. Patients undergoing multiple perioperative anticoagulation interruptions were included. ResultsOne hundred and forty‐six patients undergoing 171 periprocedural interruptions were included in our cohort. The 30‐day rates of VTE and major bleeding were both 4.1% (95% confidence interval [CI] 2.0‐8.2). The 30‐day rate of CRNMB was 2.9% (95% CI 1.3‐6.7) and the 30‐day overall mortality rate was 0.6% (95% CI 0.1‐3.4). There were no fatal postoperative VTE or major bleeding events. ConclusionsThe periprocedural interruption of anticoagulation in patients with cancer‐associated VTE is associated with high postoperative rates of VTE and major bleeding. Patients with cancer‐associated VTE may require closer follow‐up for VTE and bleeding complications after invasive procedures.

Cancer-Associated Thrombosis and Bleeding Risk in Gastrointestinal Malignancies with Apixaban and Rivaroxaban Compared to Low Molecular Weight Heparin

Background: Randomized control trials (RCT) have examined the safety and efficacy of direct oral anticoagulants (DOACs) compared to dalteparin in patients with cancer-associated thrombosis (CAT). Increased major bleeding (MB) was seen with edoxaban and increased clinically relevant non-major bleeding (CRNMB) was seen with rivaroxaban and there has been specific concern about increased risk of bleeding among patients with gastrointestinal malignancies (GIM). Results from RCTs comparing apixaban to dalteparin in CAT are pending.Objective: Using the Mayo Clinic VTE registry, we examined the rates of MB, CRNMB, and overall bleeding (MB + CRNMB) in patients with GIM treated with anticoagulation for CAT.Methods: Consecutive patients treated for CAT were enrolled into Mayo Clinic VTE Registry between March 1, 2013 and July 27, 2018 and were followed prospectively for safety and efficacy. Clinical, demographic and imaging data were collected from each participant at the time of study recruitment. Cancer type, stage, and treatment with chemotherapy were recorded. Major and CRNMB events were evaluated at 3-month intervals. Clinical status was assessed by written questionnaire in subjects unable to return at 3 months. Unreturned questionnaires were followed up with a scripted phone interview. The study was approved by Mayo Clinic Institutional Review Board.Results: In the 535 subjects in the registry with CAT, the mean age (64.6 vs. 62.8 years), mean BMI (28.4 vs. 28.8), and percent female (46.4% vs 40.6%) were numerically similar between DOAC and LMWH treatment groups (Table 1). Metastatic disease was present in 53.6% and 60.2% and chemotherapy was being administered in 66.5% and 71.2% of DOAC and LMWH treated patients, respectively. Thrombocytopenia (<100x109/L) at initiation of anticoagulation was present in 6.8% of DOAC treated and 7.5% of LMWH treated patients. Among all cancer patients, 110 (21%) patients had a GIM, 58 (53%) were treated with LWMH and 52 (47%) were treated with a DOAC (42% rivaroxaban or 58% apixaban). In all CAT, the rate of MB was similar in DOAC versus LMWH treated patients (7.8 vs. 5.4 per 100 person-years; HR 1.48, 95% CI 0.72-3.05; Table 2). The rate of CRNMB however, was significantly increased in the DOAC patients compared to LMWH treated patients (6.18 vs. 0.44 per 100 person-years; HR 14.7, 95% CI 1.92, 112.26). In the sub-group of patients with GIM, the rate of MB was non-significantly higher in the DOAC versus LMWH treated patients (11.1 vs. 3.9 per 100 person-years; HR 2.90, 95% CI 0.57, 14.73). In contrast to the overall CAT group, the rate of CRNMB was similar in the DOAC compared to LMWH treated patients (2.10 vs. 1.92 per 100 person-years; HR 1.18, 95% CI 0.07, 20.21). In GIM patients, apixaban compared to rivaroxaban had a numerically higher, but non-significant, rate of major bleeding (23.98 vs. 3.50 per 100 person-years; HR 4.0, 95% CI 0.54-29.87). In the overall group of CAT, the risk of major bleeding was similar between apixaban and rivaroxaban (9.51 vs. 6.77 per 100 person-years).Conclusion: In our registry of subjects with CAT, we identified a significantly increased rate of CRNMB and overall bleeding, but not MB with the use of DOACs. In our data, GIM alone does not appear to account for the increased bleeding risk seen in CAT with DOACs, as we demonstrated no significant increase in major, CRNMB, or overall bleeding compared to LMWH. Direct comparison between apixaban and rivaroxaban was limited by sample size and number of events. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Periprocedural Interruption of Anticoagulation in Patients with Cancer-Associated VTE: An Analysis of Thrombotic and Bleeding Outcomes

Background: Approximately 10-20% of patients with venous thromboembolic events (VTE) have underlying malignancy. VTE is considered the second leading cause of death in patients with cancer, and patients with cancer-associated VTE are at higher risk of anticoagulant-related bleeding. Although patients with cancer often undergo diagnostic or therapeutic invasive procedures, there is a paucity of data on adverse outcomes following the periprocedural interruption of anticoagulation in this patient population.Methods: We did a single-center, retrospective chart review of consecutive patients with cancer-associated VTE who had periprocedural interruption of anticoagulation for invasive procedures between November 2015 and March 2018. Perioperative interruption of warfarin/low-molecular-weight heparin was done as per CHEST guidelines (Douketis et al. Chest 141(2 Suppl). Heparin bridging anticoagulation was used only for patients with recent (< 3 months) VTE. Perioperative interruption of direct oral anticoagulants (DOACs) was done as per Thrombosis Canada guidelines, with anticoagulation held for 3 half-lives prior to low bleeding risk procedures and 5 half-lives for high bleeding risk procedures. Active cancer was defined as per the HOKUSAI VTE CANCER trial (Raskob et al. NEJM 378(7)). Primary outcomes were 30-day post-operative rates of VTE and major bleeding. Secondary outcomes were 30-day post-operative rates of clinically relevant non-major bleeding (CRNMB) and mortality. Major bleeding and CRNMB were defined according to ISTH definitions. Data are reported on a per-interruption basis. Herein, we present an interim analysis of results.Results: To date, 82 perioperative interruptions are included, of whom 69.5% were receiving a DOAC. Mean age of the cohort was 65.8 years, 62.2% were male, 92.6% had active cancer and 41.5% had metastatic cancer. Thrombocytopenia (platelet count < 100 x 106/L) was present in 12.2% of interruptions. Procedures were stratified as high bleeding risk in 65.9% of cases. The 30-day rates of thromboembolism and major bleeding were both 3.70 % (95% confidence interval [CI] 1.25 to 10.2%), as was the 30-day rate of CRNMB. There were no deaths during the 30-day follow-up period.Conclusions: The periprocedural interruption of anticoagulation in patients with cancer-associated VTE appears to be associated with high rates of post-operative thrombotic and bleeding complications. Prospective studies are required to better quantify the risks of periprocedural anticoagulation interruption in this patient population. DisclosuresShaw:Portola Pharmaceuticals: Research Funding. Douketis:BMS: Other: Advisory Board; Janssen: Consultancy; Bayer: Other: Advisory Board; Pfizer: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Portola: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; Biotie: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; The Medicines Company: Other: Advisory Board. Carrier:Pfizer: Honoraria; Bayer: Honoraria; BMS: Honoraria, Research Funding; Leo Pharma: Research Funding.

Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D).

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.

Bleeding and Thrombotic Outcomes Following Perioperative Interruption of Direct Oral Anticoagulants in Patients with Prior Venous Thromboembolic Disease

▪Introduction: The use of Direct Oral Anticoagulants (DOACs) for the prevention and treatment of Venous Thromboembolic Disease (VTE) is increasingly common. Patients on longstanding anticoagulation for the prevention of VTE frequently undergo invasive procedures that necessitate interruption of anticoagulation in order to avoid excessive bleeding during the procedure. There is little evidence surrounding the safety of perioperative DOAC interruption in patients with VTE.Methods: This study represents a retrospective analysis of adult patients on DOAC therapy for prior VTE, who underwent temporary interruption of anticoagulation therapy for inpatient or outpatient invasive procedures. The timing to hold and resume DOAC anticoagulation was based on the estimated half-life of the DOAC, as well as the bleeding risk of the procedure (Standard vs High). Our primary outcomes included the 30-day thromboembolic complication rate, as well as the 30-day major bleeding rate (ISTH non-surgical and surgical major bleeding criteria). Secondary outcomes included clinically relevant non-major bleeding (CRNMB) and overall mortality.Results: To date, a total of 87 patients have been included in the analysis, 68% of which were male. The mean age of the cohort was 58.3 years. All patients were on DOAC anticoagulation for acute treatment or secondary prevention of recurrent VTE. A large majority of patients (94%) were anticoagulated with rivaroxaban. Procedures were performed on an inpatient or outpatient basis in 24 and 63 patients, respectively. Forty six patients underwent procedures with standard bleeding risk. Mean time to anticoagulation discontinuation for standard and high bleeding risk procedures was 41.3 (SD = 20.8) and 49.3 (SD = 17.7) hours, respectively. The 30-day thromboembolic complication rate was 1.2% (95% CI: 0.2 to 6.2%), whereas the 30-day major bleeding rate was 0% (95% CI: 0 to 4.2%). The rate of CRNMB was 3.5% (95% CI: 1.2 to 9.7%). Overall mortality was 0% (95% CI: 0 to 4.2%).Conclusion: The perioperative interruption of direct oral anticoagulation for invasive procedures in patients with prior VTE appears to be associated with a relatively low risk of major bleeding, as well as recurrent VTE. Prospective studies are needed to evaluate the benefits and risks of perioperative interruption of direct oral anticoagulation in patients with prior VTE. DisclosuresCarrier:BMS: Research Funding; Leo Pharma: Research Funding.