DOAC Group Research Articles

Antithrombotic therapy in patients with atrial fibrillation after myocardial infarction and percutaneous coronary intervention

Abstract Background Antithrombotic treatment with oral anticoagulants is recommended in clinical practice guidelines for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and concurrent atrial fibrillation (AF). Previous randomized controlled trials comparing warfarin and DOAC have primarily focused on bleeding complications. Consequently, the benefits and risks in an all-comer population remain uncertain. Purpose This study aimed to evaluate adherence to clinical practice guidelines within a large nationwide cohort and to compare outcomes among patients with MI and AF who were treated with dual antiplatelet therapy (DAPT), Warfarin, or DOAC. Method We utilized data from the nationwide SWEDEHEART registry to identify all patients with MI and AF between January 2010 and January 2021. We included all patients who underwent PCI and had a CHA2DS2-VASC score of ≥2 for men and ≥3 for women. The follow-up was one year. Patients were allocated into one of three antithrombotic treatment groups based on discharge medications: (1) Warfarin-based, (2) DOAC-based, and (3) DAPT only. The warfarin- and DOAC-based groups comprised patients on either dual or triple antithrombotic therapy. Study outcomes included: (1) major adverse cardiovascular events (MACE), defined as a composite of all-cause death, MI, or stroke; (2) net adverse cardiovascular events (NACE), which included MACE and bleeding complications; and (3) the individual components of MACE and NACE. Cox regression models were used to adjust for differences in baseline characteristics. Results Mean age among the 12,321 patients included was 76.1 years. At discharge, 3,563 (29%) were treated with warfarin, 3,671 (30%) received DOAC treatment, and 5,087 (41%) with DAPT alone. The percentage of patients treated with OAC increased from 30% in 2010 to 84% in 2021. Warfarin- and DOAC-based strategies were associated with lower MACE compared to DAPT alone, with adjusted hazard ratios [HR] (95% CI) of 0.77 (0.69-0.97) and 0.78 (0.69-0.90), respectively, as well as lower rates of NACE with adjusted [HR] (95% CI) of 0.84 (0.76-0.93) 0.84 (0.75-0.94), respectively. This difference was primarily driven by a difference in mortality, with adjusted ]HR] (95% CI) of 0.78 (0.67-0.91) and 0.80 (0.68-0.94), respectively. There were significantly fewer stroke events in the DOAC group (2.5 % vs 3.3%) compared with DAPT. No significant differences in bleeding events were observed between any of the treatment groups. Conclusions In this real-life retrospective study, we observed an increased utilization of guideline recommended OAC treatment over time. Both DOAC and warfarin treatment regimens were associated with a lower incidence of MACE and NACE compared to DAPT alone. No significant difference in outcomes were observed comparing DOAC vs Warfarin.

Direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension patients: A retrospective cohort study

IntroductionDirect oral anticoagulants (DOACs) are increasingly prescribed for life-long anticoagulation in chronic thromboembolic pulmonary hypertension (CTEPH) patients, despite not being recommended in the guidelines. This study aims to evaluate the efficacy and safety of DOACs in CTEPH patients. MethodsFrom May 2013 to December 2022, patients who were first diagnosed with CTEPH in Fuwai Hospital and started long-term anticoagulation treatment with warfarin or DOACs were retrospectively included and followed up until (1) death, (2) transition to other kinds of anticoagulants, or (3) discontinuation of anticoagulation. Propensity score matching was used to balance confounding bias of baseline characteristics. All-cause death, major bleeding, clinically relevant nonmajor bleeding and venous thromboembolism (VTE) recurrence were obtained and analysed. ResultsAfter propensity score matching, 115 patients taking warfarin and 206 patients taking DOACs were included in our study and followed up for 5.5 [3.4, 7.1] years. There was no significant difference of survival between the warfarin and the DOAC group (p = 0.77). The exposure adjusted event rate of major bleeding (0.3 %/person-year vs 0.4 %/person-year, p = 0.705) and clinically relevant nonmajor bleeding (3.1 %/person-year vs 3.2 %/person-year, p > 0.999) was similar between two groups. The exposure adjusted rate of VTE recurrence was significantly higher in the DOAC group (1.5 %/person-year vs 0.3 %/person-year, p = 0.030). ConclusionIn anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

Meta-Analysis of the Safety and Efficacy of Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus.

Literature on the preferred anticoagulant for treating left ventricular thrombus (LVT) is lacking. Thus, our objective was to compare the efficacy of DOACs versus warfarin in treating LVT. Databases were searched for RCTs and adjusted observational studies that compared DOAC versus warfarin through March 2024. The primary efficacy outcomes of interest were LVT resolution, systemic embolism, composite of stroke, and TIA. The primary safety outcomes encompassed all-cause mortality and bleeding events. Our meta-analysis including 31 studies demonstrated that DOAC use was associated with higher odds of thrombus resolution (OR: 1.08, 95% CI: 0.86-1.31, p: 0.46). A statistically significant reduction in the risk of stroke/TIA was observed in the DOAC group versus the warfarin group (OR: 0.65, 95% CI: 0.48-0.89, p: 0.007). Furthermore, statistically significant reduced risks of all-cause mortality (OR: 0.68, 95% CI: 0.47-0.98, p: 0.04) and bleeding events (OR: 0.70, 95% CI: 0.55-0.89, p: 0.004) were observed with DOAC use as compared to warfarin use. Compared to VKAs, DOACs are noninferior as the anticoagulant of choice for LVT treatment. However, further studies are warranted to confirm these findings.

Heavy Menstrual Bleeding in Adolescents on Direct Oral Anticoagulants

Background Direct oral anticoagulants (DOACs) - Dabigatran, Rivaroxaban, and Apixaban - are increasingly being used in the pediatric and adolescent population. DOACs have been shown to increase the likelihood of heavy menstrual bleeding (HMB) in adult women of childbearing age, when compared to vitamin K antagonists or low molecular weight heparins (LMWH). There are limited data regarding the prevalence of HMB in the adolescent population on DOACs. Pivotal trials leading up to the approval of DOACs in the adolescent and pediatric populations also failed to prespecify prospective analyses on the impact of DOACs on HMB. The effect of HMB and its treatment burden can contribute to the compliance rates of DOACs in this population, adding to the recurrence rates of venous thromboembolism. Our study aims to assess the rate of HMB with DOAC use in adolescents by comparing the rate of HMB and its associated healthcare burden to patients on other anticoagulants. Methods This is a retrospective cohort study conducted with deidentified data obtained from the Pediatric Health Information System (PHIS) database after IRB approval. The PHIS is a comparative database with clinical and resource utilization data for inpatient, ambulatory surgery, ED, and observation unit encounters from more than 49 children's hospitals. ICD-10 codes were used to query the data for pediatric patients between the ages of 9-18 years on anticoagulant therapy from January 2020-December 2022. DOAC group was defined as patients on Rivaroxaban, Dabigatran, or Apixaban at any point in their care. The control group was defined as patients on anticoagulants other than DOACs, such as LMWH, unfractionated heparin, coumadin, and bivalirudin. Data extracted included any episode of HMB (diagnosis codes for abnormal uterine bleeding, dysfunctional uterine bleeding, menorrhagia, or heavy menstrual bleeding), risk factors for HMB other than anticoagulants, and healthcare utilization data for HMB such as number of ED visits, hospital admission and length of stay, and ICU admission. For the Descriptive statistics, demographics and clinical characteristics of the patients were described using median and interquartile range (25th percentile, 75th percentile) for continuous variables, and frequency and percentages for categorical variables, as appropriate. Control group was matched to the DOAC group by propensity score matching using nearest method with the ratio 1:5 to generate the similar pairwise comparison. Categorical variables were analyzed with the chi-square test; continuous variables were assessed by Mann Whitney U test or Kruskal-Wallis rank sum test. P-value of less than 0.05 was considered as statistically significant for the analysis. All the analysis were performed using SAS software, version 9.4 (SAS Institute, Cary, NC) and R software, version 4.2.2 Results Of the total sample size of 87,119 patients on any anticoagulant, 84,411 (96.8%) patients were in the control group and 2,708 (3.1%) in the DOAC group before propensity matching. Of the three DOACs studied, 2013 were in Rivaroxaban group (74%), followed by Apixaban (671 or 25%) and Dabigatran (24 or 1%). Rates of HMB in patients on the largest DOAC group, Rivaroxaban vs the control group, and Rivaroxaban vs Apixaban are as shown in table 1.There was no significant difference in healthcare burden between the DOAC and control groups (p-value 0.954) with no difference in length of stay between the two groups (5 days for both groups). The rate of HMB with the use of DOACs or with known risk factors of HMB on any anticoagulant is as shown in table 2. Conclusion In contrast to adult patients, our study suggests similar rates of HMB in adolescents on DOACs when compared to the control group. Rivaroxaban was the most commonly used DOAC in our data set. Though the number of patients on Apixaban was small, there was no difference in the rate of HMB between Rivaroxaban and Apixaban groups. Patients with known risk factors of HMB had an increased rate of HMB with all anticoagulants. Prospective studies are needed to further elucidate the impact of DOACs and other anticoagulants on HMB in adolescents.

661 Evaluating the Efficacy of Post-Operative VTE Prophylaxis in Fragility Hip Fractures: DOAC vs LMWH

Abstract Aim Direct oral anticoagulants (DOACs) are licensed for use as venous thromboembolism (VTE) prophylaxis in elective hip surgery however low molecular weight heparin (LMWH) is the mainstay for VTE prophylaxis in hip surgery following fragility fractures. Due to social distancing regulations during the COVID pandemic in 2021, it became increasingly difficult for community nurses to administer LMWH injections post-operatively whilst DOACs offered a less invasive alternative. This study aims to evaluate efficacy of DOACs in comparison to LMWH as VTE prophylaxis following hip surgery in fragility fractures. Method Retrospective, population-based cohort study of patients discharged on VTE prophylaxis with LMWH and DOAC in 2019 and 2021 respectively following fragility hip fracture. Data was obtained through National Hip Fracture Database and electronic medical records. Data collected included patient demographics, comorbidities, current medications, time to surgery, level of independence pre- and post-discharge and length of stay. Main outcomes assessed were incidence of VTE within 6 months. Results A total of 200 randomly selected patients were included. Following discharge, incidence of VTE was 1% in the LMWH group (n = 100) and 1% in the DOAC group (n = 100). All patients received LMWH and TED anti-embolism stockings as an inpatient. Average length of time on DOAC following discharge was 3.5 weeks. Conclusions The study shows non-inferiority of DOACs in VTE prophylaxis post-operatively when compared to LMWH. It supports a case for their use in post-operative management of fragility hip fractures. Further data surrounding compliance to DOAC following discharge will allow accurate evaluation of its efficacy.

Application of the "1-2-3-4-day" rule to stroke severity at baseline versus at 24 h to start direct oral anticoagulant for atrial fibrillation within 7 days from symptom onset.

The aim of this study is to compare the "1-2-3-4-day" rule applied to stroke severity at baseline versus at 24 h to start DOAC for AF within 7 days from symptom onset. We conducted a prospective cohort observational study based on 433 consecutive AF-related stroke patients starting DOAC within 7 days from symptom onset. Four groups were identified according to the timing of DOAC introduction: 2-day, 3-day, 4-day, and 5-7-day. Three models of multivariate ordinal regression including unbalanced variables among four groups (enrolment year, dyslipidemia, known AF, thrombolysis, thrombectomy, hemorrhagic transformation, DOAC type) were used to estimate the association of neurological severity categories (reference: NIHSS > 15) at baseline (Brant test: 0.818), at 24 h (Brant test: 0.997), and radiological severity categories (reference: major infarct) at 24 h (Brant test: 0.902) in the direction of earlier DOAC introduction on days (from 5-7-day to 2-day). Number of deaths was higher in early DOAC group than in late DOAC group according to the "1-2-3-4-day" rule (5.4% versus 1.3%, 6.8% versus 1.1%, and 4.2% versus 1.7% when it was applied to baseline neurological severity, 24-h neurological and radiological severity, respectively), but no significant difference was found and deaths were not caused by early DOAC introduction. Rates of ischemic stroke and intracranial hemorrhage were not different between early and late DOAC groups. The application of "1-2-3-4-day" rule to start DOAC for AF within 7 days from symptom onset differed when applied to baseline neurological stroke severity versus 24-h neurological and radiological severity, but safety and effecacy are similar.

Abstract WMP12: Initial Severity And Functional Outcomes Of Acute Ischemic Stroke With Atrial Fibrillation On Direct Oral Anticoagulants(DOACs): Japan Stroke Data Bank

Purpose: The purpose of this study was to examine the associations between oral anticoagulants (OACs) at onset and outcomes in acute ischemic stroke (AIS) patients with atrial fibrillation. Methods: AIS patients with comorbidity of atrial fibrillation (aged ≥18 years, pre-stroke modified Rankin Scale [mRS] 0-2) admitted within 24 hours after onset from January 2017 to December 2020 were examined from a long-lasting nationwide hospital-based multicenter prospective registry, the Japan Stroke Data Bank. Patients were classified into 3 groups according to anticoagulants at onset: no-anticoagulant group, warfarin group and DOAC group. The co-primary outcomes were the National Institutes of Stroke Scale (NIHSS) on admission and favorable outcome at discharge, corresponding to the mRS of 0-2. Mixed effects logistic regression was performed to examine the association between antithrombotic agents and these outcomes. Results: Of a total of 6,838 patients, 4,249 (62.1 %) patients were classified into the no-anticoagulant group, 907 (13.3 %) into warfarin group and 1,682 (24.6 %) into DOACs group. Median NIHSS score on admission was 7 [interquartile range: 2-19] in the warfarin group and 5 [2-15] in the DOAC group, versus 9 [3-20] in the no-anticoagulant group. Both warfarin and DOAC groups had lower NIHSS scores as compared to no-antithrombotic group (adjusted incidence rate ratio 0.96 [95% confidence interval 0.94-0.99] and 0.81 [0.79-0.83], respectively) after adjustment by age, sex, hypertension (HT), dyslipidemia (DL), diabetes mellitus (DM) and history of stroke. The rate of favorable outcome at discharge was 41.5 % in no-anticoagulant group, 42.0% in warfarin group and 48.1 % in DOACs group. In multivariable analysis, sex, NIHSS on admission, HT, DL, DM, history of stroke and intravenous thrombolysis and mechanical thrombectomy, DOACs group more frequently had favorable outcome (odds ratio 1.20 [95% CI 1.03-1.40]) than no-anticoagulant group, but warfarin group did not (1.05 [0.86-1.27]). Conclusion: Taking DOACs prior to onset appears associated with milder stroke severity and a more favorable outcome following acute ischemic stroke in patients with atrial fibrillation.

Abstract WP124: Stroke Severity And In-hospital Death In Intracerebral Hemorrhage Patients Taking Antithrombotic Agents: Japan Stroke Data Bank

Purpose: The purpose of this study was to determine the associations between antithrombotic agents at onset and outcomes in intracerebral hemorrhage (ICH) patients. Methods: ICH patients admitted within 24 hours after onset from January 2017 to December 2020 were examined from a long-lasting nationwide hospital-based multicenter prospective registry, the Japan Stroke Data Bank. Patients were classified into 4 groups according to types of antithrombotic agents at onset: no-antithrombotic, antiplatelet, warfarin, and DOAC groups. Patients with combination of antiplatelet and anticoagulant agents were classified into respective anticoagulant groups. The outcomes were NIHSS on admission, in-hospital death and unfavorable outcome corresponding to mRS of 5-6 at discharge. Results: Of a total of 9,948 ICH patients (female: 4,329, age 70±15 years old), 77.4% of patients were classified into the no-antithrombotic group, 13.0% into the antiplatelet group, 3.9% into the warfarin group and 5.7% into the DOAC group. Median NIHSS on admission was 12 (interquartile range: 5-22), 13 (5-26), 15 (5-30) and 13 (6-24), respectively. In multivariable analysis, the warfarin group was significantly associated with higher NIHSS on admission (adjusted incidence rate ratio, 1.08 [95% CI, 1.05-1.12], setting the no-antithrombotic group as reference), but the antiplatelet group (1.01 [0.99-1.03]) or the DOAC group (0.97 [0.94-1.00]) was not. The rate of in-hospital death was 13.0% in the no-antithrombotic group, 17.8% in the antiplatelet group, 27.3% in the warfarin group and 18.9% in the DOAC group and that of unfavorable outcome was 30,8%, 41.9%, 48.6% and 41.5%, respectively. In multivariable analysis, the warfarin group was significantly associated with in-hospital death and unfavorable outcome (adjusted odds ratio: 1.62 [95% CI, 1.07-2.46] and 1.79 [1.23-2.6], respectively, setting the no-antithrombotic group as reference), but the antiplatelet group (1.14 [0.87-1.36], 1.11 [0.90-1.36]) or the DOAC group (1.07 [0.72-1.60], 1.27 [0.90-1.78]) was not. Conclusion: ICH patients taking warfarin at onset had higher NIHSS on admission, in-hospital death and unfavorable outcome compared to those without antithrombotic agents, but those taking DOAC did not.

Abstract 11359: Safety and Efficacy of DOACs Compared to Vitamin K Antagonist in the Treatment of Left Ventricular Thormbus

Introduction: The Safety and efficacy of DOACs is unknown in patients with left ventricular thrombus as these patients were excluded from DOAC trials. Hypothesis: The safety and efficacy of DOACs is comparable to vitamin K antagonists Methods: Databases including Medline, Scopus and Cochrane Central Registration of Controlled Trials were queried from inception to March 30 th 2022. Studies reporting efficacy and safety outcomes were selected for the analysis. Results: We included 11 studies comprising 1920 patients with left ventricular thrombus. The mean age in the DOAC group was 57.5 years (SD 12.8) and 58.6 years (SD 13.0) in the VKA group; 26.8% were females. Pooled results showed no difference in mortality (RR, 0.64 [95% CI, 0.16-2.52]) embolic events (RR, 0.94 [95% CI, 0.59-1.50]) or major bleeding (RR, 0.95[95% CI, 0.66-1.36]) in the DOACs compared to VKA groups. Event rate for DOAC group compared to VKA group was 12.7 vs 17.5 per 100 patient-years (mean follow up of 4.0 months) for mortality, 19.5 vs 26.5 per 100 patient-years (mean follow up of 8.9 months) for embolic events and 8.0 vs 10.0 per 100 patient-years (mean follow up of 9.5 months) for major bleeding. Conclusions: These data, from observational and randomized studies, demonstrate promising safety and efficacy of DOACs for treatment of left ventricular thrombus. Elevated embolic and mortality rates regardless of anticoagulant choice emphasize the need for further research to improve outcomes for patients with this complication.

168 AN EXPLORATION OF ATRIAL FIBRILLATION AND ANTICOAGULATION IN STROKE PATIENTS WHO UNDERGO THROMBECTOMY IN A TERTIARY THROMBECTOMY CENTRE

Abstract Background Atrial Fibrillation is a significant cause of ischaemic stroke. Prevalence of atrial fibrillation in patients requiring thrombectomy is approximately 33%. Embolic thrombi which develop due to Atrial fibrillation may become targets for clot removal by thrombectomy in appropriate patients. Anticoagulation is one of the mainstays of treatment for atrial fibrillation. Methods A list of patients who had thrombectomy performed for ischaemic stroke in 2021 was compiled. Charts were reviewed to establish the prevalence of atrial fibrillation and the rates of appropriate dosing of anticoagulant. Of those who were not anticoagulated, we aimed to establish if there was a clear reason for this. This was performed in a tertiary referral centre with 24/7 access to thrombectomy. Results 97 patients had thrombectomy performed for ischaemic stroke in 2021. 34/97(35%) had atrial fibrillation (21/97 pre-existing , 13/97 newly diagnosed on admission). 15/21 were anticoagulated and 6/21 were not anticoagulated at the time of their stroke. 5/6 had a clear reason documented for stopping anticoagulation. One patient had stopped anticoagulation due to cost. Of those with atrial fibrillation who were anticoagulated at the time of their stroke, 11 were anticoagulated with a Direct-Acting AntiCoagulant (DOAC) and four were anticoagulated with Warfarin. Of the Warfarin group, just one patients’ INR was therapeutic at the time of their stroke. Of the DOAC group, all were on the appropriate dose. Conclusion Stroke patients requiring thrombectomy are a group who may suffer the largest strokes. Incidence of atrial fibrillation was similar to previous studies. It was encouraging that there was a documented reason for all patients who were not anticoagulated, and that the DOAC dose was appropriate. Issues with therapeutic levels of Warfarin are further highlighted here. This study concludes that we may not be as bad at anticoagulation as we may think.

Use of Direct Oral Anticoagulant and Associated Bleeding and Thrombotic Complication after Lower Extremity Bypass.

Therapeutic anticoagulation with either a vitamin K antagonist (VKA) or direct anticoagulant (DOAC) is often newly prescribed to patients undergoing lower extremity bypass (LEB) to aid in graft patency when risk factors for thrombosis are present or to treat postoperative venous thromboembolism or atrial fibrillation. There is a gap in knowledge as to how DOAC usage impacts postoperative outcomes compared with the standard-of-care VKAs. To determine temporal trends in DOAC prescription after infrainguinal LEB, impact on length of stay (LOS), and associated bleeding and thrombotic complications, patients undergoing elective LEB were identified from the Vascular Quality Initiative between January 2013 and May 2019. Postoperative bleeding, LOS, and graft occlusion for patients receiving VKA compared with DOAC were evaluated. A total of 24,459 LEBs were performed during the study period. Among 2,656 patients newly prescribed an anticoagulant, 78.0% (n = 2,072) received VKA and 22.0% (n = 584) received a DOAC, with DOAC use increasing throughout the study period. There was no significant difference in postoperative bleeding (VKA 2.3%, DOAC 1.7%, p = 0.413) or graft occlusion (VKA 1.2%, DOAC 1.4%, p = 0.762) between the anticoagulant classes. LOS was shorter in the DOAC group than in the VKA group (5.7 vs 6.8 days; p < 0.001). This analysis demonstrates that DOAC use is increasing with time in Vascular Quality Initiative centers. DOACs are a safe and comparable alternative to VKAs in the postoperative setting with similar rates of bleeding complications and early graft patency and are associated with a reduced postoperative LOS.

Direct oral anticoagulants compared to vitamin K-antagonists in patients with left ventricular thrombus

Abstract Background/Introduction In the setting of left ventricular thrombus (LVT), direct oral anticoagulants (DAOC) are poorly studied. Current European guidelines recommend treatment with Vitamin K antagonists (VKA) for 6 months. So far, several observational studies reported similar efficacity and safety of DOACs, compared to VKAs. Controversial findings were found in one big cohort, where higher stroke rates were reported among patients treated with DOAC compared to VKA, what raised concerns about the efficiency and safety to use DOACS in the setting of LVT. Purpose This retrospective multicenter study compared thrombus resolution and clinical outcomes of patients with LVT treated with DOACs or VKAs. Methods From an echocardiography database of three teaching hospitals in Switzerland, patients diagnosed with LVT between 2015 and 2021 were identified. All echocardiograms and outcomes were reviewed by independent physicians. Thrombus resolution rate and clinical outcomes were compared according to the underlying anticoagulation regimen. Results Overall, 101 patients (17.8% females, mean age 63.3±13.2 years) were included. Among those, 50.5% had a recent myocardial infarction, 38.6% chronic ischemic heart disease and 10.9% suffered from non-ischemic cardiomyopathy. At hospital discharge, 48 (47.5%) were treated with DOACs and 53 (52.5%) with VKAs. Initial left ventricular ejection fraction was 38±13%. 93.1% patients presented with apical wall motion abnormalities, mean wall motion score index was 1.91±0.39. Initial thrombus size was comparable in both groups (table 1). Median follow-up was 799 (354; 1236) days and the clinical composite endpoint combining stroke, systemic embolism, bleedings, myocardial infarction and death was comparable in the VKA (22.6%) and DOAC (27.1%) group, respectively. There was no difference in major (4% vs. 6.3%) and minor (13.5% vs. 4.3%) bleeding events, neither for stroke and systemic thromboembolism (14.3% vs 14.9%) or death (11.3% vs 8.5%). Thrombus resolution rate after 1 year was similar in the VKA and DOAC group (75.5% vs. 76.7%), but early thrombus dissolution within the first month was faster in the VKA arm (p=0.049). In each group, 3 subjects had thrombus recurrence after cessation of anticoagulation. Conclusion Among patients with LVT, DOACs appear to be a safe and effective alternative to vitamin K antagonists, but thrombus seems to dissolve slower in the first month. An adequately powered randomized trial is needed to confirm these findings. Funding Acknowledgement Type of funding sources: None.

Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors.

IntroductionCardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting.MethodsTo investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period.ResultsWhile no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = −3.33 (0.60), P < 0.001 and dipyridamole: B = −3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = −2.69 (0.74), P < 0.001 and dipyridamole: B = −17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B−3.12 (1.42), P = 0.012] and stroke [B = −3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = −17.05 (1.01), P < 0.001].ConclusionLate cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.

Survival outcomes with warfarin compared with direct oral anticoagulants in cancer-associated venous thromboembolism in the United States: A population-based cohort study.

BackgroundDirect oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established.Methods and findingsUtilizing the United States’ Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied.ConclusionsIn this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE.

PO-718-05 PRESCRIBING PATTERNS OF DIRECT ANTICOAGULANTS VERSUS VITAMIN K ANTAGONISTS IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION AND EXTREME OBESITY

Anticoagulation is an effective treatment in prevention of stroke in patients with atrial fibrillation (AF). Direct anticoagulants (DOACs) have been favored over vitamin K dependent antagonists (VKAs) given their safety and efficacy. However, there is limited real-world data on DOAC use among patients with extreme obesity. Describe the prescribing patterns of DOACs versus VKAs in patient with non-valvular AF (NVAF) and extreme obesity and the efficacy and safety of DOACs. Using a retrospective cohort study design, patients with NVAF, receiving oral anticoagulants (DOACs versus VKA), and extreme obesity (BMI ≥ 40 kg/m2 and/or weight ≥ 120 kg) during 2014 to 2020 at large healthcare system are included. Primary efficacy outcome is ischemic stroke and primary safety outcome is major bleeding. Sociodemographic and clinical characteristics were compared between DOAC and VKA groups using chi-square test for categorical variables and student’s t-test for continuous variables. Cox proportional hazards model is used to compare the primary efficacy and safety outcomes between the groups. Of the 6,930 patients, about two-third (63%) were prescribed DOACs. Patients receiving VKA were significantly older in age compared to DOAC group (66.1 (±10.2) vs 62.9 (±10.7); P=0.0321). There were no statistically significant differences in DOAC prescription by gender, race, and BMI. Even among patients with a BMI >=50, DOAC prescription rate was 61%. Across three categories of CHA2DS2VASc score (i.e., < 2, 2-4 and ≥ 5), the rate of DOAC prescription ranged from 80% to 65% and 52% respectively. Patients with higher CHA2DS2VASc score were significantly more likely to receive a VKA prescription than DOACs (P < 0.001). A third of this study patients were on concomitant antiplatelet agents with a trend towards DOACS prescribing pattern (59% vs 41%, 0.0361). In Cox regression, DOACs were associated with a significantly lower risk of ischemic stroke (hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.42, 0.65) and major bleeding (HR: 0.55; 95% CI: 0.59, 0.90) compared to VKA. Despite lack of safety and efficacy data from clinical trials, in this extreme obese group of NVAF patients, DOACs were preferred over VKAs without an increase in stroke or major bleeding events.

Increased relative risk of delayed hemorrhage in patients taking anticoagulant/antiplatelet medications with concurrent aspirin therapy: implications for clinical practice based on 3-year retrospective analysis in a large health system.

The incidence of delayed posttraumatic intracranial hemorrhage (DH) in patients on anticoagulant (AC) and antiplatelet (AP) medications, especially with concurrent aspirin therapy, is not well established, with studies reporting disparate results with between 1-10% risk of DH and 0-3% mortality. The purpose of this 3-year retrospective study is to evaluate the true risk of DH in patients on AP/AC medications with or without concurrent aspirin therapy. One thousand forty-six patients taking AP and AC medications presenting to network emergency departments with head trauma who had repeat CT to evaluate for DH were included in the study. Repeat examinations were typically performed within 24h (average follow-up time was 21h and 99% were within 3days). Mean time to DH was 20h. All positive studies were reviewed by two board-certified neuroradiologists. Patients were excluded from the study if hemorrhage was retrospectively identified on the initial examination. Cases were reclassified as negative if hemorrhage on the follow-up examination was thought to be not present or artifactual. Cases were considered positive if the initial examination was negative and the follow-up examination demonstrated new hemorrhage. Overall, there was 1.91% incidence (20 patients) of DH and 0.3% overall mortality (3 patients). The group of patients taking warfarin or AP agents demonstrated a significantly higher rate of DH (3.2% compared to 0.9%) and higher mortality (0.9% compared to 0.0%) compared to the DOAC group (p < 0.01). The risk of DH in patients taking AC or AP agents with aspirin (13/20 cases) was significantly higher (RR 3.8, p < 0.01) than that of patients taking AC or AP alone (7/20 cases). The risk of DH was significantly higher in patients taking aspirin in addition to AC/AP medications. Repeat imaging should be obtained for trauma patients taking AC/AP agents with concurrent aspirin. The rate of DH was also significantly higher in patients taking warfarin or AP agents when compared to patients taking DOACs. Repeat examination should be strongly considered on patients taking warfarin or AP agents without aspirin. Given the relatively low risk of DH in patients taking DOACs alone, repeat imaging could be reserved for patients with external signs of trauma or dangerous mechanism of injury.

Incidence of Device-Related Thrombosisin WatchmanPatients Undergoing a Genotype-Guided Antithrombotic Strategy.

This study sought to report the incidence of device-related thrombosis (DRT) and thromboembolic (TE) events when an alternative to clopidogrel is prescribed in loss-of-function (LOF) allele carriers of the cytochrome P450 2C19 (CYP2C19) gene. LOF polymorphisms of the CYP2C19 gene are associated with reduced hepatic bioactivation of clopidogrel. A total of 1,002 Watchman patients were included. Six hundred forty-five patients underwent CYP2C19 genetic testing; among patients with clopidogrel resistance, clopidogrel was replaced by either prasugrel (pilot cohort) or half dose direct oral anticoagulant ([DOAC]/Group 1), both in combination with aspirin. We compared the incidence of DRT/TE events among genotyped patients and a control group which received standard dual antiplatelet therapy (DAPT) (Group 2; n=357). All reported events occurred during a timeframe between 45- and 180-day follow-up transesophageal echocardiograms, when the 2 different antithrombotic strategies (genotype-guided vs standard DAPT) were adopted. In the pilot cohort (n=244), bleeding events occurred in 10.2% of patients who received aspirin plus prasugrel, leading to early discontinuation of the prasugrel-based protocol. DOAC Group 1 patients (n=401), 25.7% were reduced metabolizers, and clopidogrel was replaced by half dose direct oral anticoagulant. DRT was documented in 1 (0.2%) patient of Group 1 and 7 (1.96%) patients of Group 2 (log-rank P =0.021). The composite endpoint of DRT/TE events was significantly loweramong patients receiving a genotype-guided antithrombotic strategy (0.75% vs 3.10%; log-rank P =0.017). In Watchman patients, a genotype-based antithrombotic strategy with aspirin plus half dose DOAC in reduced clopidogrel metabolizers was superior to standard DAPT with respect to DRT/TE events.

Abstract 10243: Meta-Analysis of Direct Oral Anticoagulants versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Valves

Objective: The optimal anticoagulation strategy for patients with bioprosthetic valves and atrial fibrillation remain uncertain. Thus, we conducted a meta-analysis using updated evidence comparing direct anticoagulants (DOAC) and vitamin K antagonist (VKA) in patients with bioprosthetic valves and atrial fibrillation. Methods: MEDLINE and EMBASE were searched through March, 2021 to identify randomized control trials (RCT) and observational studies that investigated the outcomes of DOAC and VKA in patients with bioprosthetic valves and atrial fibrillation. The outcomes of interest were all-cause death, major bleeding, and stroke or systemic embolism. Results: Our analysis included 4 RCTs and 6 observational studies which enrolled a total of 6,405 patients with bioprosthetic valves and atrial fibrillation assigned to the DOAC group (n =2,142) and VKA (n =4,263). Pooled analysis demonstrated the similar rates of all-cause death (HR [95% confidence interval [CI]] =0.90 [0.77-1.05]; P =0.18; I 2 =0%)between the DOAC and VKA groups. However, the rates of major bleeding were significantly lower in the DOAC group compared to the VKA group (HR [95% CI] =0.66 [0.48-0.89]; P =0.006; I 2 =0%) (Figure), while the rates of stroke or systemic embolism were similar (HR [95% CI] =0.72 [0.44-1.17]; P =0.18; I 2 =39%). Conclusion: DOAC was associated with lower rates of major bleeding without increasing the risk of stroke or systemic embolism or all-cause death compared to VKA in patients with bioprosthetic valves and atrial fibrillation.

Direct oral anticoagulants or low-molecular-weight heparins for venous thromboembolism in patients with brain tumors

IntroductionPatients with central nervous system malignancies have limited representation in studies evaluating DOACs for VTE treatment. This study evaluated the safety and efficacy of DOACs in comparison with LMWH for cancer-associated VTE in patients with primary brain tumors or secondary brain metastases. Materials & methodsIn 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 treatment of cancer-associated VTE were evaluated. The primary outcome was the cumulative incidence of any intracranial hemorrhage within a 6-month period following the initiation of anticoagulation. Secondary outcomes included the cumulative incidence of any bleeding event, and recurrent VTE events. ResultsBetween January 1, 2012 and October 9, 2019, one-hundred eleven patients met inclusion criteria. The 6-month cumulative incidence of intracranial hemorrhage was 4.3% (95% CI, 0.74–13.2%) in the DOAC group, compared to 5.9% (95% CI, 1.5–14.9%) in the LMWH group (p = 0.61). The 6-month cumulative incidence of bleeding events was 14.3% (95% CI, 6.2–25.8%) in the DOAC group, compared to 27.8% (95% CI, 15.5–41.6%) in the LMWH group (p = 0.10). The 6-month cumulative incidence of recurrent VTE events was 5.6% in the DOAC group (95% CI, 1.5–14.2%), compared to 6.6% in the LMWH group (95% CI, 1.7–16.5%) (p = 0.96). No differences were found with respect to other secondary outcomes. ConclusionThere were no significant differences in bleeding or recurrent VTE events between DOACs and LMWH. These findings suggest DOACs may be safe and effective for VTE treatment in this patient population.

Left atrial appendage closure: a new strategy for cardioembolic events despite oral anticoagulation.

Patients with non-valvular atrial fibrillation (nvAF) who experienced a cardioembolic (CE) event despite adequate oral anticoagulation (OAC) are at high risk of recurrence, and further prevention strategies are deemed necessary. The present study aimed to evaluate the safety and efficacy of off-label use of left atrial appendage closure (LAAC) in this subset of patients. Seventy-five consecutive patients with nvAF who experienced a CE event despite adequate OAC therapy were retrospectively enrolled from two Italian centers. Patients were divided according to the treatment strategy following the index event: DOAC group (49 patients who continued OAC therapy with DOACs) and LAAC group (26 patients who underwent LAAC procedure). 1:1 propensity-score matching between the two groups was performed. LAAC group was made up of two subgroups according to the post-procedural pharmacological regimen: 1) dual antiplatelet therapy (DAPT) for 3 months followed by indefinite single antiplatelet therapy (LAAC+SAPT); or 2) aspirin plus DOAC for 3 months followed by indefinite DOAC therapy (LAAC+DOAC). The primary endpoint was a composite of CE event, major bleeding, or procedure-related major complication. During a median follow-up of 3.4 years (IQR: 2.0-5.3), LAAC was a predictor of primary endpoint-free survival (HR=0.28, 95% CI: 0.08-0.97; P=0.044); within LAAC group, no procedure-related major complication occurred. Moreover, a trend toward a lower rate of both CE events and major bleedings was observed in LAAC group, particularly in the subgroup LAAC+DOAC. LAAC is a reasonable therapeutic option in nvAF patients who suffered a CE event despite adequate OAC therapy.