Anticoagulation in Cancer Patients with Atrial Fibrillation and Grade 3-4 Thrombocytopenia

Abstract Introduction: Atrial fibrillation (AF) is not uncommon in cancer patients with grade 3-4 thrombocytopenia (platelets <50x10 9/L). The risk of bleeding appears to outweigh the risk of thrombosis in acute leukemia patients. There are no published data regarding management of anticoagulation (AC) and rates of bleeding and thrombosis in other cancer types. Aim: To assess AC management and incidence of bleeding and thrombosis in thrombocytopenic cancer patients with AF. Methods: Single-center retrospective cohort study. The study included adults with active cancer, grade 3-4 thrombocytopenia (platelets <50x10 9/L) and AF with CHA 2DS 2-VASc ≥1, irrespective of AC status prior index. Patients with acute leukemia were excluded. Patients were indexed when platelets <50x10 9/L. AC management was classified as either "No-AC", if AC was withheld (i.e., stopped or not started) at index, or "Continue-AC", if AC was continued. Arterial thromboembolism (ATE; ischemic stroke, transient ischemic attack or systemic embolism) and ISTH-defined major bleeding were recorded over 30 days. The 30-day cumulative incidence of composite and individual outcomes with corresponding 95% confidence intervals (CI) was calculated for each management group (death as competing risk). A Cox proportional hazards model was used to calculate hazard ratios (HR) and corresponding 95% CI for outcomes between the No-AC and Continue-AC groups, with death as a competing risk (Fine and Gray model). Results: The eligibility criteria were met by 131 patients. At study index, AC was not given in 90 (69%) patients and continued in 41 (31%). Table 1 shows patient characteristics overall and stratified for management. The median age was 80 years )IQR 70-82) and 55 (42%) were females. Most patients were inpatients at index (70%) and had newly diagnosed cancer (70%). 64% had solid malignancy, and the remainder had hematological malignancy. The majority (92%) had AF prior to study index, while 8% had AF newly diagnosed at index. The median CHA 2DS 2-VASc score was 4 [IQR 3-5] and 18% had a prior stroke. Median platelet counts were 42 x 10 9/L at index and the median HASBLED score was 5 [3-5]. Only 44% of the No-AC group were receiving AC prior index, compared with 95% in the Continue-AC group, at shorter median duration. The type of prior AC differed between groups. Antiplatelet therapy (54%) and major bleeding prior index (13%) were more frequent in the No-AC group. There was a median [IQR] of 4 [0-60] and 4 [1-26] days of grade 3-4 thrombocytopenia in the No-AC and Continue-AC groups, respectively. Platelet nadirs (x10 9/L) were numerically higher in the No-AC group (31 [3-50] vs. 21 [6-50]; p=0.09). A median [IQR] of 12 [6-17.25] and 10 [5-12] platelet transfusions were given to 29 (32.2%) patients in the No-AC group and 11 (26.8%) in the Continue-AC group, respectively (p>0.2). In the Continue-AC group, AC was subsequently held in 12/41 (29%) and dose-reduced in 4/41 (10%) during the 30 days post-index. The 30-day cumulative incidence [95% CI] of the composite outcome (major bleeding or ATE) was 10% [4.88-17.27] in the No-AC group and 4.88% [0.86-14.7] in the Continue-AC group (HR 2.142 [0.47-9.609]). The 30-day cumulative incidence of ATE (Figure 1A) was 3.33% [0.88-8.66] in the No-AC group (n=3), and 4.88% [0.85-14.7] in the Continue-AC group (n=2), corresponding with a HR of 0.70 [0.12-4.10]. The 30-day cumulative incidence of major bleeding (Figure 1B) was 7.8% [3.40-14.52] in the No-AC group, and 2.44% [0.18-11.22] in the Continue-AC group (HR 3.29 [0.42-26.04]). The 30-day overall survival was 64.4% in the No-AC and 73.2% in the Continue-AC groups (HR 1.39 (95% CI 0.7-2.76). Conclusions: In a cohort of cancer patients with grade 3-4 thrombocytopenia (<50x10 9/L) and AF (median CHA 2DS 2-VASc = 4), the majority had anticoagulation held. Baseline thrombotic and bleeding risk factors were generally balanced, but a higher rate of prior bleeding and lower rates of anticoagulation prior index in the No-AC group, suggest confounding by indication. No statistically significant difference in outcomes was detected between management groups, but 95% CI's were wide. The high bleeding and low ATE incidence in the No-AC group suggests that holding AC during time-limited periods of grade 3-4 thrombocytopenia may be a reasonable approach in many cancer patients with AF. Continuing AC should be investigated in a subset of patients with lower bleeding and higher thrombotic risk. Figure 1 Figure 1. Disclosures Falanga: Pfizer: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Leo Pharma: Honoraria. ten Cate: Bayer AG: Other; Pfizer: Other; LEO Pharma: Other; Gideon Pharmaceuticals: Other; Alveron Pharma: Other. Leader: Bayer: Honoraria; Leo Pharma: Honoraria; Novartis: Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Honoraria.

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Thrombotic Risk Assessment in a Prospective Cohort of Newly Diagnosed Ambulatory Cancer Patients Candidate to Chemotherapy

Blood ◽

10.1182/blood-2019-129901 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3642-3642

Author(s):

Anna Falanga ◽

Cristina Verzeroli ◽

Marina Marchetti ◽

Cinzia Giaccherini ◽

Laura Russo ◽

...

Keyword(s):

Risk Assessment ◽

High Risk ◽

Cancer Patients ◽

Cumulative Incidence ◽

Prospective Cohort ◽

Tumor Site ◽

Newly Diagnosed ◽

Thrombotic Risk ◽

D Dimer

Introduction: The occurrence of venous thromboembolism (VTE) during chemotherapy may result in treatment delays with unfavorable effects on cancer outcome, therefore VTE prevention is a relevant issue. Current guidelines recommend primary thromboprophylaxis in select high-risk cancer outpatients undergoing chemotherapy. Hence, the use of risk assessment models involving both clinical and biological parameters is increasingly important. In this analysis, in a large prospective cohort of patients with newly diagnosed metastatic non-small cell lung (NSCLC), colorectal (CRC), gastric (GC) or breast (BC) cancers, we assessed whether pre-chemotherapy levels of thrombotic biomarkers may help to stratify patients at different risk levels of VTE during the first 6 months of anti-tumor therapy. Methods: The study cohort included patients with advanced cancer enrolled from January 2012 to December 2017 in the HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815), an ongoing Italian prospective, multicenter, observational study (Falanga et al, Thromb Res 2016). Clinical data and blood samples were collected at enrollment and during scheduled follow-up visits. Baseline plasma levels of fibrinogen (Clauss method), d-dimer (immunoturbidimetric assay), prothrombin fragment F1+2 (ELISA), FVIIa-AT (ELISA) and thrombin generation (TG, CAT assay) were measured. The study protocol was approved by the local Ethics Committee. Informed written consent was obtained from all study subjects. The outcome measure of the current analysis is the time to the occurrence of first symptomatic and/or incidental VTE, objectively confirmed. Results: A cohort of 922 patients [median age: 66 (30-92) years] with metastatic NSCLC (n=416), CRC (n=262), GC (n=105) and BC (n=139) was available for analysis. After a median follow-up of 327 days (range 44-1,548), VTE occurred in 122 (76 M/46 F) patients [median age 64 y (range 40-85)] providing a cumulative incidence of 19.7% (CI 95%: 16-23). According to tumor site, VTE frequency was: NSCLC (n= 64, 15.3%) > CRC (n= 38, 14.5%) > GC (n= 12, 11.4%) > BC (n= 8, 5.7%). Biomarkers' analysis of baseline plasma samples from 598 patients showed significantly higher levels of fibrinogen, d-dimer and TG in the cancer cohort compared to healthy control subjects (p<0.01). NSCLC patients had significantly (p<0.001) higher levels of d-dimer compared to CRC and BC patients, and of fibrinogen (p<0.001) compared to CRC, BC and GC patients. Cumulative incidence of VTE at 6 months was 10% (CI 95% 8-12). In particular, patients who had VTE in 6 months presented with significantly higher pre-chemotherapy levels of D-Dimer than VTE-free subjects (p<0.05). Cox-multivariate analysis identified as independent risk factors for VTE, high d-dimer (HR: 2.1, CI 95% 1.2 - 3.7; p=0.008), high peak of TG (HR: 1.8, CI 95% 0.99 - 3.2; p=0.052), and site of primary tumor (non-BC vs BC) (HR: 3.3, CI 95% 1.01 - 10.5; p=0.048). A score for VTE prediction was created with these variables and three risk categories (low, intermediate, and high) were generated. The cumulative incidence of VTE at 6 months in each risk category was 3.9%, 9.8%, and 19%, respectively (low vs high HR: 2.36 p=0.005; intermediate vs high HR 2.16 p=0.006). Differently, the application of the Khorana score failed to identify high risk patients. Conclusions: Our prospective study in a large cohort of metastatic cancer patients shows the high burden of VTE during the first 6 months of chemotherapy. Furthermore, laboratory data from this analysis enable us to create a risk scoring system based on d-dimer and TG together with tumor site, that significantly identifies patients at the highest VTE risk. Further investigation are worth to externally validate this score for clinical use. Project funded by AIRC "5xMILLE multiunit extension program" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)". Disclosures Santoro: Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; MSD: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BMS: Consultancy; Abb-Vie: Speakers Bureau; Roche: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; BMS: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Lilly: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Sandoz: Speakers Bureau; Takeda: Speakers Bureau.

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Etiology, Diagnostic Workup and Incidence of Thrombosis in Patients with Splenic Infarcts

Blood ◽

10.1182/blood-2021-153384 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1053-1053

Author(s):

Avi Leader ◽

Ela Giladi ◽

Lihi Pertman ◽

Shlomit Tamir ◽

Avishay Elis ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Cumulative Incidence ◽

Antithrombotic Therapy ◽

Primary Outcome ◽

Newly Diagnosed ◽

Thrombotic Risk ◽

Diagnostic Work ◽

Work Up ◽

Diagnostic Work Up

Abstract Introduction: There are knowledge gaps regarding splenic infarcts (SI), given the heterogenic patient population and wide range of clinical presentation. Comprehensive data on the frequency, management and outcomes of cryptogenic SI are lacking. Aim: To assess the etiology, treatment patterns and outcome of patients with SI, with an emphasis on cryptogenic SI. Methods: Single-center retrospective cohort study including adults with acute symptomatic or incidental SI. Patients were indexed at SI diagnosis and records were followed for 12 months. Patients were identified by ICD-9 diagnoses and an electronic search of the text in all radiology reports, and confirmed by manual review. Thrombotic risk-factors were classified as "baseline" if known at index or as "newly-diagnosed" if identified in diagnostic tests that were performed or recommended during hospitalization for the index SI. Diagnostic work-up was performed according to the clinician's discretion. The clinical context as well as baseline and newly-diagnosed thrombotic risk factors were used to determine SI etiology at baseline. Patients with no clear SI etiology after workup were classified as cryptogenic. Imaging studies of patients with cryptogenic SI were manually reviewed by an abdominal radiologist to identify possible etiology. The study exposure was the type of antithrombotic therapy defined as the prescribed antithrombotic regimen at discharge from hospitalization for the index SI, and classified as follows: none; anticoagulation (AC) only; antiplatelet (APT) only; AC & APT. AC was defined as intermediate or full dose AC. Prophylactic dose AC was classified as no AC. The primary outcome was arterial thromboembolism (ATE; acute coronary syndrome, ischemic stroke; transient ischemic attack; systemic embolism including recurrent SI) or venous thromboembolism (VTE) during 12-month follow-up. The cumulative incidence of the primary outcome over 12 months and corresponding 95% confidence intervals (CI) was calculated for each antithrombotic therapy group and a Cox proportional hazards model was used to calculate hazard ratios (HR), with death as a competing risk. Results: The eligibility criteria were met by 255 patients. The median age was 66 years and 130 (51%) were female. At least one cardiovascular risk factor was present in 221 (87%) patients. while 44 (17%) had previously diagnosed atrial fibrillation. 30 (12%) patients had prior VTE and 83 (33%) had acute concurrent ATE or VTE diagnosed at another site during hospital admission for the index SI. The SI etiology after initial diagnostic work-up, stratified for type of antithrombotic therapy at hospital discharge, is shown in Table 1. The most prevalent presumed etiologies were active malignancy in 92 (36%), cardioembolic in 69 (27%), infection in 48 (19%), shock/hypoperfusion in 47 (18%) and abdominal surgery in 46 (18%). Myeloproliferative neoplasms (2%) and antiphospholipid syndrome (6%) were rare causes. Only 15 cases (6%) were cryptogenic. Radiology review identified a possible etiology that was missed on initial review in 5 (33%) of the 15 cryptogenic SI's. These etiologies were cardioembolic [n=3], infectious [1] and malignancy [1]. Diagnostic work-up post-SI led to identification of a previously undiagnosed thrombotic risk factor in 58 cases (23%), especially atrial fibrillation (8%) and malignancy (10%), as shown in Table 2. The yield of antiphospholipid antibody testing was 10%, after confirmatory testing (Table 2). 148 patients (58.0%) were discharged from hospital with antithrombotic therapy (Table 1). The overall 12-month cumulative incidence of ATE or VTE was 18% [95% CI 13.5-23%]. Figure 1 shows the cumulative incidence of VTE or ATE stratified for type of antithrombotic therapy. The APT only and AC & APT groups had the highest 12-month incidence of ATE/VTE (22% [11.7-34.4%] and 27.4% [14.1-42.6%], respectively). In the cryptogenic SI group, 9 (60%) received AC and 4 (27%) patients had ATE/VTE. Conclusions: SI is associated with a wide spectrum of clinical disorders. Cryptogenic SI is rare and imaging review may identify possible etiologies in such cases. Diagnostic workup leads to identification of new thrombotic risk factors in 1 in 4 patients and should be pursued. The rate of ATE or VTE at 12-months post-SI is high despite antithrombotic therapy. Further research is needed to identify the optimal antithrombotic therapy in these patients. Figure 1 Figure 1. Disclosures Leader: Leo Pharma: Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Honoraria; Bayer: Honoraria; Sanofi: Honoraria.

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Addition of Mycophenolate Mofetil to Methotrexate and Tacrolimus Does Not Improve Gvhd Outcomes in Reduced Intensity Allogeneic Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v126.23.3144.3144 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3144-3144

Author(s):

Se young Han ◽

Pavan Kumar Bhamidipati ◽

Khoan Vu ◽

John F Dipersio ◽

Feng Gao ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Cumulative Incidence ◽

Research Funding ◽

Univariate Analysis ◽

Competing Risk ◽

Gvhd Prophylaxis ◽

Significant Difference ◽

Risk Event ◽

Grade 3 ◽

Reduced Intensity

Abstract Introduction: The introduction of reduced intensity conditioning (RIC) regimens, associated with less NRM, has significantly broadened transplant eligibility to older patients. However, graft-versus-host disease (GVHD) continues to be a major problem, even with RIC allo-HCTs. At our institution, we have been routinely adding mycophenolate mofetil (MMF) to the standard methotrexate (MTX) plus Tacrolimus combination in the majority of RIC allo-HCT recipients from unrelated donors. However, there is a paucity of data on whether this approach further decreases GVHD rates without increasing NRM and risk of relapse. To answer these questions, we retrospectively analyzed data from 177 patients who received MMF, MTX and Tacrolimus (MMF + Tac/MTX) as part of their GVHD prophylaxis and compared their outcomes to those of 117 patients who received MTX and Tacrolimus alone (Tac/MTX). Patients and methods: The study included a total of 294 consecutive patients who underwent RIC allo-HCT at Washington University Medical Center between January 2006 and December 2013. The data was analyzed for patients who received GVHD prophylaxis with either tacrolimus/methotrexate (Tac/MTX) or tacrolimus/mycophenolate mofetil/methotrexate (MMF+Tac/MTX). Cumulative incidence of relapse was estimated treating death in remission as competing risk event. Cumulative incidence of NRM was calculated considering death in relapse as competing risk event. Univariate analysis was performed to evaluate variables, and multivariate Cox models with a backward selection procedure were done to assess whether GVHD prophylaxis was an independent predictor after adjusting other factors significant in the univariate analysis. All analyses were two-sided, and significance was set at a p-value of 0.05. Statistical analyses were performed using library cmprsk in statistical package R for competing risk analysis and SAS 9.4 (SAS Institutes, Cary, NC) for all other analyses. Results: 177 patients (60.2%) received MMF+Tac/MTX whereas 117 patients (39.8%) received Tac/MTX. Median age was 61 years in the MMF+Tac/MTX group and 58 years in the Tac/MTX group, and the most common diagnosis was AML(31%) followed by NHL (26%) and MDS (19%) in the MMF+Tac/MTX group vs. AML (45%) followed by MDS (14%) and NHL (13%) in the Tac/MTX group. There were more transplants from unrelated and mismatched donors, higher intermediate ASMBT RFI risk group patients and more frequent use of conditioning with Flu/Bu/Thymo regimen in the MMF+Tac/MTX cohort. In particular 160 (90.4%) patients in MMF+Tac/MTX group received thymoglobulin as part of their conditioning, compared to 64 (54.7%) patients in the Tac/MTX group (p < 0.001). The cumulative incidence of grade 2-4 aGVHD at day 100 was 31.0% in the MMF+Tac/MTX group vs. 36.2% in the Tac/MTX group (p=0.191) while as grade 3-4 aGVHD at day 100 and 1 year were 16.8% and 25.9% in the Tac/MTX group compared to 8.0% and 12.4% in the MMF+Tac/MTX group, respectively (p=0.010). However, after adjusting for the thymoglobin use there was no significant difference in the incidence of grade 3-4 aGVHD in these two groups (p=0.129). To eliminate the confounding effect of thymoglobulin, we performed a subgroup analysis of patients without thymoglobulin. Given the small number of samples (n=17 in MMF+Tac/MTX and n=53 in Tac/MTX), propensity score matching was used and the results again showed no significant difference in severe aGVHD between two groups (p=0.219). The incidence of cGVHD at 1 year was 15.3% and 21.6% in MMF+Tac/MTX and Tac/MTX, respectively (p=0.645). Although patients in the MMF+Tac/MTX group had more unfavorable disease risk, the cumulative incidence of relapse at 3 years was not significantly different: 40.8% in the MMF+Tac/MTX group and 39.8% in the Tac/MTX group (p=0.941). 5-year OS was 33.7% in the MMF+Tac/MTX group, compared to 35.1% in the Tac/MTX group (p=0.769). Conclusion: Here we report transplant outcomes of RIC allo-HCT patients who received MMF in addition to Tac/MTX for GVHD prophylaxis. Interestingly we did not see any increase in NRM or relapse rates with additional immune-suppression from adding MMF in these patients. However, addition of MMF to the Tac/MTX regimen did not result in any significant improvement in acute or chronic GVHD outcomes in our patients. Based on these results we do not recommend adding MMF to Tac/MTX regimen for GVHD prophylaxis in RIC allo-HCT patients. Disclosures Uy: Novartis: Research Funding. Schroeder:Incyte: Consultancy; Celgene: Other: Azacitidine provided for this trial by Celgene. Abboud:Pfizer: Research Funding; Merck: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Teva Pharmaceuticals: Research Funding; Gerson Lehman Group: Consultancy. Cashen:Celgene: Speakers Bureau.

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Rivaroxaban for Stroke Prevention in Patients with Non-Valvular Atrial Fibrillation and Active Cancer

Blood ◽

10.1182/blood.v128.22.2621.2621 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2621-2621 ◽

Cited By ~ 2

Author(s):

Eva Simona Laube ◽

Anthony Yu ◽

Dipti Gupta ◽

Yimei Miao ◽

Patrick Samedy ◽

...

Keyword(s):

Atrial Fibrillation ◽

General Population ◽

Competing Risks ◽

Major Bleeding ◽

Cumulative Incidence ◽

Research Funding ◽

Chronic Phase ◽

Systemic Embolism ◽

Safety And Efficacy ◽

Active Cancer

Abstract BACKGROUND: The link between aging, cancer and atrial fibrillation is well known and the appropriate anticoagulation management of non-valvular atrial fibrillation (NVAF) in patients with active cancer is of growing clinical concern. Rivaroxaban has been broadly used for the primary prevention of stroke and systemic embolism in the general population of patients with NVAF. However, individuals with a serious concomitant illness associated with a life expectancy of less than 2 years were excluded from pivotal trials including the ROCKET-AF study, limiting the generalizability of results to patients with active cancer. There is little published evidence on the safety and efficacy of rivaroxaban for NVAF in this specific subgroup. OBJECTIVES: The aim of this study was to assess the safety and efficacy of rivaroxaban in patients with active cancer and NVAF. METHODS: The use of rivaroxaban in cancer patients at Memorial Sloan Kettering Cancer Center (MSKCC) was monitored in the setting of a Quality Assessment Initiative. Patients with active cancer and NVAF treated with rivaroxaban from 1/1/2014 through 3/31/2016 are included in this analysis. Endpoints of interest were defined a priori and include stroke, systemic embolism, major bleeding and clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days (CRNMB). Clinical events were assessed through text searches of medical records. The analysis was performed respecting different times on previous anticoagulation, considering the first 90 days as the acute phase of treatment and contrasting it with the subsequent chronic phase. RESULTS: A total of 163 evaluable patients were included in the analysis, with a median age of 72.0 years (interquartile range=67.0-77.5 years) and 56% of these individuals being men. The majority had a solid tumor (85%), with stage IV disease reported in 50% of cases. The mean CHA2DS2-Vasc score was 3.2 (standard deviation=1.5) and 64% of patients were already in the chronic phase of anticoagulation. Results for the acute, chronic and combined phases of anticoagulation are presented in the Table and plotted in the Figure. The estimated cumulative incidence of ischemic stroke, major bleeding, and CRNMB at 1 year were 1.4% (95% CI=0-3.4%), 1.2% (95% CI=0-2.9%) and 14.0% (95% CI=4.2-22.7%) respectively, after adjusting for competing risks. Interestingly, the cumulative incidence of major bleeding in our cohort is lower than the value reported for the ORBIT-AF registry of cancer patients on dabigatran or a vitamin K antagonist for NVAF, in which the estimated rate of this complication was 5.1/100 patient-years. Lastly, the 1-year cumulative incidence of mortality was 22.6% (95% CI=12.2-31.7%). This high risk of death was present throughout the observation period and reflects the cancer population. One patient died after developing an acute ischemic cerebrovascular insult and a myocardial infarction. There were no deaths related to bleeding and no recorded systemic embolism episodes. CONCLUSIONS: The safety and efficacy profile of rivaroxaban treatment for NVAF in patients with active cancer seems comparable to what was observed for the general population in the ROCKET-AF study, but ideally a prospective study would be required to confirm these findings. Table Cumulative Incidence of Competing risks for Patients in the Acute, Chronic and Combined Phases of Anticoagulation* *Cumulative incidence estimates for the chronic phase are conditional to reaching day 90 of anticoagulation without sustaining an event. The chronic phase was defined as lasting 275 days and the combined period encompasses 365 days. CRNMB: Clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days. *Clinically-relevant non-major bleeding leading to discontinuation of rivaroxabanfor at least7 days. Table. Cumulative Incidence of Competing risks for Patients in the Acute, Chronic and Combined Phases of Anticoagulation*. / *Cumulative incidence estimates for the chronic phase are conditional to reaching day 90 of anticoagulation without sustaining an event. The chronic phase was defined as lasting 275 days and the combined period encompasses 365 days. / CRNMB: Clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days. / *Clinically-relevant non-major bleeding leading to discontinuation of rivaroxabanfor at least7 days. Figure Figure. Disclosures Yu: Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Soff:Janssen Scientific Affairs, LLC: Consultancy, Research Funding. Mantha:Janssen Scientific Affairs, LLC: Research Funding.

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Abstract P146: Comparative Effectiveness Of Direct Oral Anticoagulants Versus Warfarin Among Medicare Beneficiaries With Atrial Fibrillation

Circulation ◽

10.1161/circ.143.suppl_1.p146 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Shirin Ardeshirrouhanifard ◽

Huijun An ◽

Ravi Goyal ◽

Mukaila Raji ◽

Caleb Alexander ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Cancer Patients ◽

Risk Model ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Competing Risk ◽

Secondary Outcome ◽

Systemic Embolism ◽

Competing Risk Model

Objective: Post-hoc analysis of three pivotal clinical trials suggests no difference in risk of ischemic stroke or systemic embolism among cancer patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) vs. warfarin. However, these studies were underpowered and also do not reflect the context of real-world use. We compared the effectiveness of DOACs versus warfarin for the risk of stroke or systemic embolism and all-cause death in patients with NVAF. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus) and NVAF. We limited the cohort to patients who newly initiated warfarin or DOACs (from 2010 to 2016) with no history of ischemic stroke or systemic embolism. The primary outcome was hospitalization due to ischemic stroke or systemic embolism and the secondary outcome was all-cause death. We used Fine and Gray’s competing risk model, while treating death as a competing risk, to determine the association of oral anticoagulants with the incidence of stroke or systemic embolism. We also adjusted the analysis using inverse probability of treatment weighted (IPTW). Additionally, an IPTW-adjusted Cox proportional hazards regression model was constructed for all-cause death. Results: Of 1,028,784 patients with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 7,334 cancer patients diagnosed with incident NVAF who newly initiated warfarin or DOACs, of which 3,194 (43.6%) used warfarin and 4,140 (56.4%) used DOACs. The unadjusted rate of stroke or systemic embolism was similar among warfarin and DOACs users (1.20 vs. 1.32 cases per 100 person-years, p=0.27). In the IPTW weighted competing risk model, the use of DOACs was not associated with an increased risk of stroke or systemic embolism compared with warfarin users (Hazard Ratio [HR] 1.41, 95% confidence intervals [CI] 0.90-2.20). However, DOACs users had a significantly lower risk of all-cause death compared with warfarin users (HR 0.82, CI 0.74-0.91). Conclusion: Among cancer patients diagnosed with NVAF, DOACs had a similar risk for stroke or systemic embolism compared to warfarin, although DOAC use was associated with reduced risk of all-cause mortality.

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Abstract 15467: Impact of Thrombocytopenia on Clinical Outcomes in Atrial Fibrillation Patients With Anemia: The Fushimi Af Registry

Circulation ◽

10.1161/circ.142.suppl_3.15467 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kenjiro Ishigami ◽

Syuhei Ikeda ◽

KOSUKE DOI ◽

Yasuhiro Hamatani ◽

Akiko Fujino ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Outcomes ◽

Major Bleeding ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Antithrombotic Drugs ◽

Prospective Survey ◽

Kaplan Meier ◽

Significant Difference ◽

Independent Determinant

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p<0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.

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Rivaroxaban Versus Warfarin for Management of Obese African Americans With Non-Valvular Atrial Fibrillation or Venous Thromboembolism: A Retrospective Cohort Analysis

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620954910 ◽

2020 ◽

Vol 26 ◽

pp. 107602962095491

Author(s):

Olivia S. Costa ◽

Jan Beyer-Westendorf ◽

Veronica Ashton ◽

Dejan Milentijevic ◽

Kenneth Todd Moore ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

African Americans ◽

Major Bleeding ◽

Cox Regression ◽

Cohort Analysis ◽

Bleeding Risk ◽

Nonvalvular Atrial Fibrillation ◽

Thrombotic Risk ◽

Hazard Ratios

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m2 and ≥12-months EHR activity with ≥1-encounter before OAC initiation. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). For the NVAF analysis, 1,969 rivaroxaban- and 1,969 warfarin-users were matched. Rivaroxaban was not associated with a difference in stroke/systemic embolism versus warfarin (HR = 0.88, 95%CI = 0.60-1.28), but less major bleeding (HR = 0.68, 95%CI = 0.50-0.94) was observed. Among 683 rivaroxaban-users with VTE, 1:1 matched to warfarin-users, rivaroxaban did not alter recurrent VTE (HR = 1.36, 95%CI = 0.79-2.34) or major bleeding (HR = 0.80, 95%CI = 0.37-1.71) risk versus warfarin at 6-months (similar findings observed at 3- and 12-months). Rivaroxaban appeared to be associated with similar thrombotic, and similar or lower major bleeding risk versus warfarin in these obese, AA cohorts.

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Is there a correlation between the aggressiveness of chronic asymptomatic prostatitis NIH category IV and the Gleason score in patients with prostate cancer?

Canadian Urological Association Journal ◽

10.5489/cuaj.6284 ◽

2019 ◽

Vol 14 (11) ◽

Author(s):

Erdogan Aglamis ◽

Cavit Ceylan ◽

Mustafa Akin

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Gleason Score ◽

Needle Biopsy ◽

Newly Diagnosed ◽

Prostate Needle Biopsy ◽

Retrospective Design ◽

Biopsy Specimens ◽

Grade 3 ◽

Prostatic Inflammation

Introduction: We evaluated the correlation between the International Society of Urological Pathology (ISUP) grades and the aggressiveness grades of prostate inflammation in newly diagnosed prostate cancer patients with chronic asymptomatic prostatitis National Institiutes of Health (NIH) category IV (CAPNIHIV). Methods: The study comprised 357 consecutive patients with prostate cancer in whom a cancer diagnosis had been made via a prostate needle biopsy. Histological sections of the prostate biopsy specimens of the patients were reviewed and scored. Prostatic inflammation was scored using the aggressiveness grade of inflammation. The associations between the ISUP grades and the aggressiveness grades of inflammation were analyzed using logistic regression. The limitations of the study were its retrospective design and the limited number of cases. Results: In 110 (31%) patients, CAPNIHIV was detected: 56 (51%) patients had a grade 0 aggressiveness score, 34 (31%) patients had a grade 1 aggressiveness score, and 20 (18%) patients had a grade 2 aggressiveness score. The patients who had prostatic inﬂammation had a 1.65 times (95% conﬁdence interval [CI] 1.05–2.61) greater likelihood of a high ISUP grade (grade ≥3) compared with the patients who did not have prostatic inﬂammation. The association between the ISUP grade and the aggressiveness grade of inflammation was more pronounced for a grade 2 aggressiveness score (n= 20; odds ratio 2.97; 95% CI 1.14–7.71). Conclusions: In prostate cancer patients with CAPNIHIV, there was a positive correlation between the inflammation aggressiveness grade and the ISUP grade. The aggressiveness of intraprostatic inflammation may be an important morphological factor affecting the Gleason score.

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Sepsis associated new onset atrial fibrillation; risk factors and long term outcomes

European Heart Journal ◽

10.1093/ehjci/ehaa946.0363 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

V Moosavi ◽

M Paymard ◽

R Ebrahimi ◽

T Harvey ◽

N Parkes ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Major Bleeding ◽

Rate Control ◽

Statistical Significance ◽

Significant Difference ◽

All Cause Mortality ◽

New Onset

Abstract Background Atrial fibrillation (AF) is commonly encountered in the setting of systemic inflammation or infection. The optimal management of AF in this cohort and their long-term AF-related clinical outcome are unknown. Purpose The aims of our study were to evaluate the traditional and non-traditional AF risk factors and long-term AF-related clinical outcomes in patients who were diagnosed with new onset AF in the setting of sepsis. Methods In this retrospective cohort study, we used the medical records to identify patients who were diagnosed with the new onset AF during hospitalization for sepsis at our centre between 2013 and 2017. The primary clinical outcomes included 24-month risk of ischaemic stroke, major bleeding (gastrointestinal or intracranial bleeding), the recurrence of AF and the all-cause mortality. The patients with known AF or those who died during the index admission were excluded from the analysis. Results 5598 patients were admitted to our hospital between 2013 and 2017 with sepsis. Of this cohort, 126 patients (mean age 69.7 years, 62.7% male) developed new onset AF during the index hospital admission (72.2% required ICU admission). 38 patients (30.1%) died during the initial hospitalisation while 88 patients (69.9%) were discharged from hospital (32% anticoagulated). 14 patients (16%) died within 24 months. Hypertension (59%), CKD (30%), diabetes (21%), and CCF (17%) were the most common risk factors. Mean CHA2DS2VASC score was 2.56±1.4 and mean HAS BLED score was 2.5±1.3. Mean CRP and WCC were 228±119 and 12.3±9.1 respectively. Comparing risk factors, only HASBLED score showed statistical significance on 24 months mortality (p=0.036, 95% CI 0.43–1.52). The composite incidence of all-cause mortality and ischaemic stroke was three times lower in anticoagulated patients compared with those who did not receive anticoagulation even though this did not reach statistical significance (7.1% v 21.6% respectively, p=0.07; RR=0.32; 95% CI=0.79–1.36). There was no statistically significant difference between the two groups for major bleeding events (3.5% v 3.3% respectively, p=0.68; RR=1.07; 95% CI=0.10–11.3). Rhythm and rate control therapies showed no significant difference on the composite outcome of all-cause mortality, ischaemic stroke and recurrence of AF (28.0% v 28.9%, p=0.92; RR=0.96, 95% CI=0.49–1.88), however, there was a trend towards less recurrence of AF in patients who received rate or rhythm control therapies (12% vs 18% respectively p=0.44; RR=0.67; 95% CI=0.24–1.85). Conclusions Our study suggests that anticoagulation therapy in patients with sepsis associated new onset AF may decrease composite of all-cause mortality and ischaemic stroke without increasing major bleeding risk. Rhythm and rate control strategies did not decrease all-cause mortality, ischaemic stroke or risk of recurrence of AF. These findings can provide benchmarks for design of randomized control trials. Funding Acknowledgement Type of funding source: None

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Premature permanent discontinuation of apixaban or warfarin in patients with atrial fibrillation

Heart ◽

10.1136/heartjnl-2020-317229 ◽

2020 ◽

pp. heartjnl-2020-317229 ◽

Cited By ~ 1

Author(s):

Anthony P Carnicelli ◽

Sana M Al-Khatib ◽

Denis Xavier ◽

Frederik Dalgaard ◽

Peter D Merrill ◽

...

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Major Bleeding ◽

Study Drug ◽

Treatment Groups ◽

Patient Request ◽

Clinical Events ◽

Significant Difference ◽

Ischaemic Attack

AimsThe ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial randomised patients with atrial fibrillation at risk of stroke to apixaban or warfarin. We sought to describe patients from ARISTOTLE who prematurely permanently discontinued study drug.Methods/ResultsWe performed a posthoc analysis of patients from ARISTOTLE who prematurely permanently discontinued study drug during the study or follow-up period. Discontinuation rates and reasons for discontinuation were described. Death, thromboembolism (stroke, transient ischaemic attack, systemic embolism), myocardial infarction and major bleeding rates were stratified by ≤30 days or >30 days after discontinuation. A total of 4063/18 140 (22.4%) patients discontinued study drug at a median of 7.3 (2.2, 15.2) months after randomisation. Patients with discontinuation were more likely to be female and had a higher prevalence of cardiovascular disease, diabetes, renal impairment and anaemia. Premature permanent discontinuation was more common in those randomised to warfarin than apixaban (23.4% vs 21.4%; p=0.002). The most common reasons for discontinuation were patient request (46.1%) and adverse event (34.9%), with no significant difference between treatment groups. The cumulative incidence of clinical events ≤30 days after premature permanent discontinuation for all-cause death, thromboembolism, myocardial infarction, and major bleeding was 5.8%, 2.6%, 0.9%, and 3.0%, respectively. No significant difference was seen between treatment groups with respect to clinical outcomes after discontinuation.ConclusionPremature permanent discontinuation of study drug in ARISTOTLE was common, less frequent in patients receiving apixaban than warfarin and was followed by high 30-day rates of death, thromboembolism and major bleeding. Initiatives are needed to reduce discontinuation of oral anticoagulation.

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