Efficacy Of Apixaban Research Articles

Validation of the Safety and Efficacy of Apixaban as Postoperative Thromboembolism Prophylaxis for Patients with Gynecologic Malignancies.

Venous thromboembolism is a preventable complication of gynecologic cancer surgery that leads to postoperative morbidity and mortality. This study compared apixaban with enoxaparin to identify whether apixaban had the same safety and efficacy for patients undergoing gynecologic cancer surgery. The study identified patients with a gynecologic malignancy who underwent surgery and were prescribed apixaban at discharge between June 2020 and April 2023. International Classification of Diseases 10 codes were used to identify patients who had a thromboembolism within 90 days or a bleeding event within 60 days after surgery. The rates of events for patients prescribed apixaban were compared with those for a historical cohort of patients who received enoxaparin. Fisher's exact tests were used to compare categorical variables, and t tests were used to compare continuous variables. A logistic regression was performed to compare the odds of thromboembolism between the two groups. Baseline patient characteristics differed in terms of body mass index (BMI), race, route of surgery, and type of cancer. Of the 490 patients in the apixaban cohort, 12 (2.4%) had a thromboembolism compared with 3 (2.1%) of the 138 patients in the enoxaparin group (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI] 0.30-4.70; p > 0.999). The odds ratio was adjusted for BMI, age, and route of surgery. A bleeding event occurred for 1 (0.2%) of the 490 patients in the apixaban group and for 1 (0.7%) of the 138 patients in the enoxaparin group. This validation study showed that apixaban is a safe and effective method of postoperative venous thromboembolism prophylaxis. The data provide support to previous data and guideline updates recommending the use of apixaban for postoperative prophylaxis.

Efficacy and safety of Apixaban in the treatment of cerebral venous sinus thrombosis: a multi-center study.

Information regarding the safety and efficacy of specific direct oral anticoagulants (DOAC) in the treatment of cerebral sinus and venous thrombosis (CSVT) is scarce. Apixaban is one of the most frequently prescribed DOACs. Therefore, we aimed to compare the safety and efficacy of Apixaban with those of vitamin k antagonists (VKA) in patients with CSVT. Prospective CSVT databases from seven academic medical centers were retrospectively analyzed. Patients treated with Apixaban were compared to those treated with VKA. Data on demographics, clinical presentations, risk factors, radiological and outcome parameters were studied. Overall, 403 patients were included in the analysis. Of them, 48 (12%) were treated with Apixaban, and 355 (88%) were treated with VKA. Rates of coagulopathies were significantly higher in the VKA-treated patients but no other differences between the groups were found in baseline characteristics and underlying etiology. No significant differences were found between groups in efficacy or safety parameters including the rates of recanalization, favorable outcomes, one-year mortality, seizures, intracranial hemorrhage or CSVT recurrences. Our data suggests that Apixaban may be safe and effective for patients with CSVT. These results should be tested in prospective randomized clinical studies.

Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices: The DOAC LVAD Study

BackgroundPatients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described. ObjectivesThis study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non–central nervous system thromboembolism) as compared with treatment with warfarin. MethodsThe DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome. ResultsA total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources. ConclusionsAnticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978)

Safety and efficacy of apixaban vs. enoxaparin in thromboprophylaxis after spinal stenosis and degenerative spine surgery

IntroductionDegenerative spine surgeries often require postoperative immobilization or reduced mobility, predisposing patients to the formation of thrombosis and higher risk of thromboembolic complications. Despite the significance of this issue, there remains a lack of consensus on the optimal anticoagulant agent for postoperative thromboprophylaxis in spinal stenosis and degenerative spine surgeries. Low molecular weight heparins and direct Xa inhibitors represent two anticoagulant groups with high chemoprophylactic potential. MethodsThis study included a prospective cohort of patients undergoing posterior decompressive surgery with or without instrumentation for degenerative spine disease and/or spinal stenosis. Patients receiving postoperative prophylactic Enoxaparin and Apixaban were selected to evaluate the rate of complications, as assessed by Clavien-Dindo classification, thromboembolic events, and 30-day mortality, readmission, and reoperation rate between the two anticoagulants. Results130 patients were included in the analysis. 65 patients received Apixaban and Enoxaparin in each group. Mean age of the participants was 57.6±11.0. 83.1% underwent laminectomy and posterior spinal fusion, while 22 patients underwent decompressive surgery only. The incidence of venous thromboembolism (P-value=0.403), deep vein thrombosis (p-value=0.999), hematoma formation (p-value=0.403), surgical site infection (p-value=0.901), readmission (p-value=0.545), reoperation (p=0.510), mortality (p=0.648), and complications rate (p-value=0.232) were not statistically different between Enoxaparin and Apixaban. DiscussionBoth Apixaban and Enoxaparin may be viable options for postoperative thromboprophylaxis in spine surgeries with comparable efficacy and safety profile. Future research endeavors should investigate the efficacy of these agents in comparison to placebo in a randomized setting.

Efficacy of Apixaban vs. Low Molecular Weight Heparin in Hip Arthroplasty and their Influence on Coagulation Function and Postoperative Deep Vein Thrombosis

Efficacy of Apixaban vs. Low Molecular Weight Heparin in Hip Arthroplasty and their Influence on Coagulation Function and Postoperative Deep Vein Thrombosis

Safety of apixaban and rivaroxaban compared to warfarin after cardiac surgery

Direct oral anticoagulants (DOACs) are frequently prescribed for the management of atrial fibrillation and venous thrombosis. There is a lack of published data on the utilization of DOACs in individuals who have undergone recent cardiac surgery. The purpose of this study was to evaluate the safety and efficacy of apixaban and rivaroxaban compared to warfarin in patients postcardiac surgery. In this retrospective cohort study, patients were separated into a DOAC cohort or a warfarin cohort based on the agent they received after cardiac surgery. Patients could be included if they were ≥18 years of age and received or were discharged on either rivaroxaban, apixaban, or warfarin within 7 days after cardiac surgery. The primary outcome for the study was the rate of International Society on Thrombosis and Hemostasis (ISTH) major bleeding during hospitalization and for 30 days following discharge or until first follow-up appointment. There were a total of 194 patients included in the analysis, 97 in the DOAC cohort and 97 in the warfarin cohort. Four patients (4.1%) in the DOAC group experienced ISTH major bleeding, while 2 patients (2.1%) in the warfarin cohort experienced ISTH major bleeding (p = 0.68). No patients in the DOAC cohort experienced a thrombotic event, whereas 2 patients (2.1%) in the warfarin cohort experienced a thrombotic complication (p = 0.5). Apixaban and rivaroxaban demonstrated similar safety when compared to a matched cohort of warfarin patients. Larger prospective randomized studies are needed to confirm these findings.

Preliminary Result of a Pilot Study of Apixaban in the Treatment of Splanchnic Vein Thrombosis

Introduction: Recently, direct oral anticoagulants (DOACs) are widely used in patients with venous thromboembolism. However, there is no sufficient data of DOACs in treatment of splanchnic vein thrombosis (SVT). In this study, we aimed to investigate the safety and efficacy of apixaban in treatment of SVT. Methods: PAINT-SVT study was a prospective pilot study of the patients with newly diagnosed symptomatic acute SVT. Patients should not have contraindication to DOACs, and appropriate liver and renal function. Patients with chronic SVT, which includes evidence of cavernous formation, collateral circulation, or known SVT within 6 months were excluded. Apixaban was administered at a dose of 10mg bid for 7 days, followed by 3 months of 5mg bid for initial treatment. With physicians’ decision, patients could be treated for 3 more months with apixaban at a dose of 2.5mg bid. Primary objective of this study was major bleeding (MB) according to International Society on Thrombosis and Haemostasis criteria. Key secondary objectives included clinically relevant non-major bleeding (CRNMB) and overall response rate (ORR). Results: From Mar 2021 to Jun 2022, a total of 21 patients were enrolled in this study. Median age was 67 (range, 44 - 81) years and 12 patients (57.1%) were males. This study included 17 patients (81.0%) with liver cirrhosis (LC), and all but one patient had child-push score of A. Four patients (19.0%) had underlying malignancies (1 lymphoproliferative disease, 1 gastrointestinal stromal tumor, 1 hepatocellular carcinoma, and 1 follicular lymphoma). With median time on anticoagulation of 92 (range, 3.0 - 184.0) days, 3 patients experienced MB and 6 patients experienced CRNMB. CRNMB occurred mostly within 1 month of anticoagulation, while MB occurred more wide range of time point during anticoagulation. Although the interpretation is limited due to the small number of samples, bleeding event occurred exclusively in LC patients. Of 21 patients, 18 patients were evaluable except for 2 patients who discontinued before the completion of initial treatment due to bleeding and 1 patient who did not completed 3 months of anticoagulation at the time of analysis. Radiologically, ORR was 61.1% including 5 patients (27.8%) with complete remission (CR) and 6 patients (33.3%) with partial remission (PR). Among 17 patients with LC, 15 patients were evaluable and ORR was 66.7% (CR, 26.7% and PR, 40.0%). Among patients who completed 3 months of initial treatment, 14 patients received additional 3 months of extended treatment and 11 patients completed extended treatment. So far, 2 patients showed improvement of response (PR to CR) and 1 patient showed thrombus progression during the treatment. Conclusions: In patients with SVT, apixaban can be used effectively and safely. However, caution is warranted for bleeding complications especially in patients with underlying LC, even in the early stage. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Prospective Study of Apixaban for Central Venous Catheter Associated Upper Extremity Deep Vein Thrombosis in Cancer Patients: Catheter 3

Introduction Upper extremity deep vein thrombosis (UEDVT) represents up to 10% of cases of venous thromboembolism (VTE) and is frequently associated with central venous catheter (CVC) placement in patients receiving chemotherapy for cancer. UEDVT may be treated with low molecular weight heparin (LMWH) either as monotherapy or subsequently transitioned to warfarin as we have previously shown (Kovacs 2007). In the Catheter 2 Study (Davies 2018) we showed that Rivaroxaban had efficacy but in the 70 patients that were included there were 6 major bleeds (8.6%) and 1 death due to pulmonary embolism (PE). Given these findings we decided to evaluate the safety and efficacy of Apixaban in the treatment of UEDVT secondary to CVC in patients with cancer. Methods We conducted a prospective cohort study at 3 centres in Canada between May 2017 and December 2021. We enrolled patients ≥18 years of age with active malignancy and symptomatic proximal UEDVT (axillary or more proximal) with or without PE, associated with a CVC. Exclusion criteria included dialysis catheters, active bleeding, platelet count <75 x 109/L, creatinine clearance <30 mL/min, PE with hemodynamic instability, inability to infuse through the catheter after a trial of intraluminal thrombolytic therapy (tissue plasminogen activator, tPa), patients with acute leukemia, patients with multiple myeloma awaiting bone marrow transplant within 3 months, thrombosis involving the brachial, basilic or cephalic veins only, treatment for >7 days with other anticoagulants, need for dual antiplatelet therapy (recent stent), or concomitant use of P-glycoprotein and CYP3A4 inhibitors. The primary objective was to estimate catheter survival at 3 months (defined as a catheter that did not develop infusion failure not responding to 2 mg of tPa). Secondary outcomes included recurrence of DVT, PE, major bleeding, clinically relevant non-major bleeding (CRNMB) and death. All events were independently adjudicated. Due to the fact that in the Catheter 2 Study most bleeds occurred while taking 15 mg bid of Rivaroxaban, for this study, patients were treated with dalteparin, 200 IU/kg x 7days followed by Apixaban 5 mg po bid to complete 12 weeks. tPa for management of blocked lines was allowed. Patients were followed clinically for 12 weeks to assess for clinical events including recurrent symptomatic VTE, major bleeding and CRNMB. Results We included 70 patients (41, 59% women) with a mean age of 62 years. DVTs were diagnosed by ultrasound and 2 patients (3%) also had PE at baseline. The most common veins involved were axillary (n=53, 76%) and subclavian (n=52, 74%), followed by the brachial, internal jugular, brachiocephalic and external jugular. Peripherally inserted central catheters (PICC) were the most common (n=56, 80%), followed by port-a-cath lines (n=14, 20%). Types of active malignancy included breast (n=22, 31%), colon (n=12, 17%), colorectal (n=7, 10%), lung (n=4, 6%), bladder (n=3, 4%), pancreatic (n=3, 4%) and other (n=19, 27%). Catheter survival was 57% at 12 weeks with no catheters removed due to thrombosis and all catheters were functional until removal or end of study. Reasons for CVC removal prior to the end of the study included end of therapeutic need (n=21), infection (n=3), accidentally fell out (n=3), patient preference (n=1), and death (n=2). One patient (1.4%) had a recurrent DVT in the same arm during the 3-month follow-up period. The 2 patient deaths were both due to underlying cancer. There were 7 bleeding events in 6 patients, 3 major (2.9%) and 4 CRNMB (5.7%). (1 patient had 2 major bleeds). Discussion In this study, Apixaban showed promise in treating CVC-associated UEDVT in cancer patients, resulting in high preserved CVC function.

The utilization and safety of apixaban for therapeutic anticoagulation in heart transplant population requiring routine endomyocardial biopsies.

Routine endomyocardial (EM) biopsies pose a challenge in the management of heart transplant recipients requiring anticoagulation. Apixaban is a direct-acting oral anticoagulant (DOAC) with a short half-life allowing for brief interruptions of anticoagulation for procedures. The study objective was to determine the safety and efficacy of apixaban in heart transplant patients undergoing EM biopsies. This retrospective case series evaluated patients with a heart transplant from April 1, 2017 to July 30, 2020 who were treated with apixaban within 90 days post-transplant. The primary outcome was the occurrence of a bleeding or thrombotic event. A total of 12 patients with >100 biopsies were included. The median age was 54 years (IQR 37-59) with a mean weight of 91±20 kg. There were no bleeding or thrombotic events. During therapy, patients underwent an average of eight biopsies. The median time from transplant to initiation of apixaban was 39.5 days (range 9-77). Therapy was maintained without any need for reversal for a median of 276 days (IQR 45-245). Apixaban is safe to use for anticoagulation of heart transplant recipients undergoing routine biopsies. Using apixaban allows for a short interruption of therapeutic anticoagulation to accommodate a biopsy without increased risk of bleeding.

OC-11: Safety and efficacy of apixaban as thromboprophylaxis in multiple myeloma patients receiving chemotherapy: a prospective cohort study

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

The Safety and Efficacy of Apixaban (Eliquis) in 5017 Post-bariatric Patients with 95.3% Follow-up: a Multicenter Study.

Thromboprophylaxis in bariatric surgery is widely debated; however, few large articles evaluate treatment plans and their efficacy. Herein, we make the first large-scale report of the safety and efficacy of apixaban (Eliquis) for thrombus prevention following bariatric surgery. To evaluate the safety and efficacy of apixaban following bariatric surgery. Three private institutes, USA. Data from 5017 consecutive bariatric patients that were placed on postoperative apixaban for thromboprophylaxis were used for retrospective analysis. The dose prescribed to patients was 2.5mg PO BID for a total of 30days starting on day 3 postoperatively. In total, of the 5017 patients, 59.7%, 31.2%, 4.4%, 2.5%, 1.8%, and 0.1% of the patients had undergone sleeve gastrectomy (SG), single-anastomosis duodeno-ileal bypass with SG (SADI-S), Roux-en-Y gastric bypass (RYGB), conversion from SG to SADI, small bowel reconstruction, and RYGB reversal, respectively. The 30-day follow-up rate was 95.3%. In total, 1.7% of patients experienced apixaban-related side effects. The most common side effects were menorrhagia and rash. Two (0.03%) side effects developed into Clavien-Dindo grade II complications. Overall, 10 (0.1%) patients experienced thromboembolic complications (five (0.09%) PVTs and five (0.09%) PEs). In each case, the protocol was not followed for extenuating circumstances. There were no deaths or thromboembolic events in cases where the protocol was able to be fully followed. In conclusion, 30days of postoperative apixaban appears to be safe and effective with minimal side effects while preventing thromboembolic events.

Safety and efficacy of apixaban as thromboprophylaxis in myeloma patients receiving chemotherapy: A prospective cohort study

•We report an amended thromboprophylactic strategy using apixaban rather than low-molecular-weight heparin for high thrombotic risk myeloma patients. •No thrombotic events are reported in patients receiving prophylactic apixaban. •Major bleeding occurred in 1.2% patients on prophylactic apixaban. •Apixaban appears to be an effective and safe alternative to low-molecular-weight-heparin as thromboprophylaxis in myeloma.

Apixaban in Japanese patients with cancer-associated venous thromboembolism: a multi-center phase II trial

Recent pivotal phase III trials involving direct oral anticoagulant (DOAC) versus low molecular weight heparin have demonstrated the utility of DOACs in Western patients with cancer-associated venous thromboembolism (VTE). However, these trials did not include Japanese patients. This phase II trial evaluated the safety and efficacy of apixaban in Japanese patients with cancer-associated VTE (UMIN000028447). Apixaban was initiated at 10mg twice daily for 7days, followed by 5mg twice daily for 23weeks. The primary endpoint was the incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. The study was terminated due to safety concerns after enrolling 27 patients. Median age was 71years; median body weight was 51.3kg; and major primary tumor sites were the gastrointestinal tract (26%) and lung (19%). During the median follow-up period of 5.4months, major or CRNM bleeding occurred in in 26% of patients (major, n = 5; CRNM, n = 2; 95% confidence interval, 11-46%). No recurrent VTE or VTE-related death occurred. Estimated overall survival at 6months was 68%. This study demonstrated the excessive bleeding risk of apixaban at the standard dose in Japanese patients with cancer-associated VTE.

Abstract 12512: Antithrombotic Strategies According to Age in Patients With Atrial Fibrillation and a Recent Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the Augustus Trial

Background: In AUGUSTUS, apixaban led to lower rates of bleeding and hospitalization than VKA, and aspirin caused more bleeding than placebo, in patients with AF and ACS and/or PCI treated with a P2Y12 inhibitor. We evaluated the safety and efficacy of different antithrombotic strategies by age in this population. Methods: Patients were stratified into 3 age groups: &lt;65, 65-74, and ≥75 years. Outcomes of interest were adjudicated ISTH major or clinically relevant nonmajor (CRNM) bleeding, ISTH major bleeding, death or rehospitalization, and death or ischemic events. The treatment effects of apixaban vs. VKA and aspirin vs. placebo were assessed across age categories using Cox models. Results: Of 4614 patients, 1267 (27.5%) were &lt;65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. All events, including bleeding, rehospitalization, and ischemic events, were more common with older age. Compared with VKA, apixaban was associated with lower rates of ISTH major or CRNM bleeding, ISTH major bleeding, and death or hospitalization, regardless of age (Fig). Apixaban was associated with greater absolute reduction in ISTH major bleeding than VKA in the older age groups, reflecting the higher bleeding risk in these groups. No differences were observed in rates of death or ischemic events between apixaban and VKA according to age. Patients who received aspirin had higher rates of bleeding than those receiving placebo in all age groups. Rates of death or rehospitalization and death or ischemic events were similar among patients receiving aspirin or placebo in different age categories. Conclusions: The safety and efficacy of apixaban compared with VKA was consistent with the overall trial findings, irrespective of age. Aspirin compared with placebo increased ISTH major or CRNM bleeding in all age groups. Our findings support the use of apixaban plus a P2Y12 inhibitor without aspirin as the standard therapy for this patient population, regardless of age. Figure: Outcomes by Age

Comparing rivaroxaban and apixaban in GARFIELD-AF according to ROCKET AF and ARISTOTLE trial selection criteria

Abstract Introduction There is debate on the extent to which differences in selection criteria and outcome definitions used for ARISTOTLE and ROCKET AF – the trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular atrial fibrillation – influenced their differences in outcomes relative to vitamin K antagonists (VKAs). In absence of randomized trials comparing the two non-vitamin K oral antagonists (NOACs) directly, this question can be addressed using data from the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) registry, a large, high-quality prospective observational study of newly diagnosed AF patients. Purpose To assess the influence of the ARISTOTLE and ROCKET AF inclusion and exclusion criteria on results for safety and efficacy of apixaban and rivaroxaban versus VKA using uniform endpoints in GARFIELD-AF. Methods We selected patients treated with apixaban, rivaroxaban or VKA from GARFIELD-AF who were eligible for ARISTOTLE or ROCKET AF as per the original trial criteria. We replicated the inclusion criteria in the GARFIELD-AF population and derived those eligible for each trial. We calculated the adjusted hazard ratios (HRs) for stroke or systemic embolism, major bleeding and all-cause mortality within 2 years of enrolment for apixaban as well as rivaroxaban versus VKA (reference) in those eligible for each trial. We used a propensity score overlap weighted Cox model to emulate trial randomization between NOAC and VKA. Results Among patients on apixaban, rivaroxaban and VKA, 2570/3615 (71%), 3560/4914 (72%) and 8005/11734 (71%) were eligible for ARISTOTLE, respectively, and 1612/3615 (45%), 2005/4914 (41%) and 4368/11734 (37%), respectively, were eligible for ROCKET AF. Cardiovascular co-morbidity was greater in those eligible for ROCKET AF than in those eligible for ARISTOTLE. In patients selected using the more restrictive ROCKET AF criteria, apixaban and rivaroxaban users showed similar results when compared with VKA (see Figure). The two sets of comparisons remained non-significant in difference when applying the less restrictive ARISTOTLE criteria, but there were trends for less similarity. Conclusion Apixaban showed similar results to rivaroxaban when selecting for higher-risk patients using the ROCKET AF criteria. In patients selected using ARISTOTLE criteria the similarity was less pronounced. Our results underline the problems faced in comparing treatments across rather than within clinical trials. For instance, co-morbidities were substantially different for patients recruited into the original ARISTOTLE and ROCKET AF trials. The current work points to the need for high-quality observational data for assessment of relative drug performance in absence of direct drug comparisons through randomized trials. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the GARFIELD-AF registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Safety and efficacy of apixaban and rivaroxaban versus warfarin in real-world atrial fibrillation patients are similar to their randomized trials: insights from GARFIELD-AF registry

Abstract Introduction Generalisability of patient selection in the landmark trials for the approval of apixaban (ARISTOTLE) and rivaroxaban (ROCKET AF) for use in non-valvular atrial fibrillation (AF) is limited. Although observational data have confirmed the safety and efficacy of these non-vitamin K oral anticoagulants (NOACs) in unselected AF populations, robust replication of randomized trials in observational studies is warranted. Purpose To investigate the proportion of real-world AF patients who would have been eligible for the landmark trials for ARISTOTLE and ROCKET AF, and to assess reproducibility of these landmark trials in the largest, worldwide, prospective registry of newly diagnosed AF patients. Methods We analysed data from the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) registry. We assessed the eligibility of AF patients treated with apixaban or vitamin K antagonist (VKA) for ARISTOTLE, and those treated with rivaroxaban or VKA for ROCKET AF, using the selection criteria of the original trials. We replicated the inclusion and exclusion criteria of ARISTOTLE and ROCKET AF by deriving the set of patients eligible for each trial and calculating the adjusted hazard ratios (HRs) for stroke or systemic embolism, major bleeding, and all-cause mortality within 2 years of enrolment, using a propensity score overlap weighted Cox model. We compared the results from observational data with those reported in the original ARISTOTLE and ROCKET AF publications. Results Among all patients enrolled in GARFIELD-AF, 67% were eligible for recruitment in ARISTOTLE and 37% in ROCKET AF. The corresponding proportions among anticoagulated patients were 70% and 39%, respectively. Among patients on apixaban and VKA, 2570/3615 (71%) and 8005/11718 (68%), respectively, were eligible for ARISTOTLE. Of patients using rivaroxaban and VKA, 2005/4914 (41%) and 4368/11721 (37%), respectively, were eligible for ROCKET AF. Annual eligibility rates among real-world NOAC users were stable over time (Figure 1). Registry participants on rivaroxaban or VKA eligible for ROCKET AF had a higher burden of cardiovascular co-morbidity than those on apixaban or VKA eligible for ARISTOTLE. The adjusted HRs in observational data were compatible with results of the original trials in all selected outcomes (Figure 2). Conclusion Representativeness of ARISTOTLE and ROCKET AF for real-world AF populations was limited, with ROCKET AF's criteria being more restrictive. Despite inclusion of only incident AF cases in GARFIELD-AF versus mostly prevalent AF cases in the original trials, the results were similar. Our work indicates that the results from ARISTOTLE and ROCKET AF appear robust and reproducible in real-world patients with newly diagnosed AF. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the GARFIELD-AF registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Cost-utility analysis of apixaban compared with usual care for primary thromboprophylaxis in ambulatory patients with cancer.

Background:Apixaban (2.5 mg) taken twice daily has been shown to substantially reduce the risk of venous thromboembolism (VTE) compared with placebo for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE. We aimed to compare the health system costs and health benefits associated with primary thromboprophylaxis using apixaban with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada’s publicly funded health care system in this subpopulation of patients with cancer over a lifetime horizon.Methods:We performed a cost–utility analysis to estimate the incremental cost per quality-adjusted life-year (QALY) gained with primary thromboprophylaxis using apixaban. We obtained baseline event rates and the efficacy of apixaban from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial on apixaban prophylaxis. We estimated relative risk for bleeding, risk of complications associated with VTE treatment, mortality rates, costs and utilities from other published sources.Results:Over a lifetime horizon, apixaban resulted in lower costs to the health system (Can$7902.98 v. Can$14 875.82) and an improvement in QALYs (9.089 v. 9.006). The key driver of cost–effectiveness results was the relative risk of VTE as a result of apixaban. Results from the probabilistic analysis showed that at a willingness to pay of Can$50 000 per QALY, the strategy with the highest probability of being most cost-effective was apixaban, with a probability of 99.87%.Interpretation:We found that apixaban is a cost-saving option for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE.

P-157: The safety and efficacy of Apixaban in patients with Multiple Myeloma on immunomodulatory therapy: real-world, single centre experience

<h3>Background</h3> Multiple myeloma (MM) is an incurable haematological malignancy associated with a high risk of venous thromboembolism (VTE). Studies have shown a significantly higher risk of VTE in MM patients compared to the general population. Moreover, it was shown that VTE in MM patients is an independent risk factor for increased mortality. Immunomodulatory agents (IMiDs) form an integral part in the treatment of MM but can be associated with a further increased risk of thrombosis especially with the addition of steroids. The incidence of VTE was quoted to be as high as 26% in one study with lenalidomide and dexamethasone combination. The IMWG recommends risk stratifying VTE thromboprophylaxis for patient treated with IMiDs to receive aspirin, low molecular weight heparin or warfarin. However, data from myeloma XI trial showed patients receiving VTE prophylaxis based on IMWG recommendations still experienced high rates of thrombosis. Since the publication of IMWG criteria, direct oral anticoagulants (DOACs) have been used as safe and effective alternatives to enoxaparin and warfarin for the treatment and prevention of VTE. Their use for VTE prophylaxis in myeloma lacks randomised comparisons with conventional approaches. <h3>Methods</h3> We present our experience on the use of apixaban for VTE prophylaxis in MM patients treated with IMiDs as an alternative to standard thromboprophylaxis. We conducted a retrospective observational analysis of VTE prophylaxis for all myeloma patients treated with IMiDs at the Royal Derby Hospital between October 2019-October 2020. Data were collected from electronic patient records. We analysed 115 episodes of IMiDs use in 109 patients (72 males and 44 females). The median age was 73 (range 42-89). Apixaban was used in 63 patients (54.8%). The remainder received enoxaparin (4,3.4%), antiplatelets (40, 34.8%), enoxaparin and antiplatelets (7, 6%) or warfarin (1, 0.8%). 44 (42%) patients were treated with IMiDs at 1st line whilst 72 (68%) were treated at relapse. The median number of lines of therapy was 2 (range 1-6). <h3>Results</h3> The number of thrombotic events on treatment was 6 (5.2%); 4 VTEs (2 PEs and 2 DVTs) and 2 arterial events (1 stroke and 1 NSTEMI) with one patient in each group on apixaban. The incidence of thrombotic events with apixaban was 1.7% vs. 3.4% with non-DOAC prophylaxis. Patients developed venous and arterial thrombotic events after a median of 2 (range 1-3) and 2.5 (range 1-4) lines of therapy respectively. VTE occurred on VTD and on lenaldiomide and dexamethasone chemotherapy in 1 and 3 patients respectively. Both arterial events occurred on lenalidomide and dexamethasone. There were no major haemorrhagic events. <h3>Conclusion</h3> Although this is a retrospective comparison of apixaban against a heterogenous non-DOAC prophylaxis arm, apixaban showed lower rates of thrombosis with no increased bleeding. Our analysis supports apixaban as a safe and effective alternative to conventional thromboprophylaxis.

Successful Use of Apixaban for Paget-Schroetter Syndrome in a Pediatric Patient.

Paget-Schroetter syndrome (PSS) is a rare syndrome that typically develops in young, healthy males subjected to repetitive overhead motions resulting in compression and thrombosis of the subclavian vein. This "effort thrombosis" typically occurs acutely in patients with specific anatomic variations within the thoracic outlet and is treated by a combination of surgical and pharmacologic interventions. There is a paucity of literature regarding this syndrome, particularly surrounding pharmacotherapy, and in the treatment of pediatric patients. This case report documents the pharmacologic treatment of a 17-year-old, male, baseball player with confirmed PSS. Apixaban was selected as the anticoagulant therapy of choice following the determination of its safety and anticipated efficacy for this pediatric patient. Upon admission, anticoagulation was initiated with intravenous heparin and transitioned to warfarin for 1 dose. On day 2, the patient was discharged with apixaban 10 mg twice daily for 7 days, followed by 5 mg twice daily. One week later, he underwent catheter-directed thrombectomy, followed by thoracic outlet decompression with resection of the first rib. Apixaban therapy was continued for 10 weeks after the procedure to diminish the risk of any further thrombotic events. This pediatric patient with PSS was successfully treated with apixaban in conjunction with surgical management. Treatment with apixaban resulted in continued resolution of thrombus after follow-up, with no complications reported thereafter. Further research is needed to definitively determine the safety and efficacy of apixaban for the use of pediatric anticoagulation, particularly in upper extremity deep vein thrombosis.

Apixaban Is Safe and Effective Thromboprophylaxis in Myeloma Patients Treated with Immunomodulatory Therapy

IntroductionPatients with myeloma are at increased risk of venous thromboembolism (VTE) and arterial thrombosis, particularly when treated with immunomodulatory drugs (IMiDs) such as thalidomide or lenalidomide. The optimal approach to prevent such potentially fatal complications has not been determined. Despite routine thromboprophylaxis with aspirin, low molecular weight heparin (LMWH) or warfarin, thrombosis rates of thrombosis of 2-8% are reported in the literature. Current agents have limited efficacy with significant associated burdens such as repeated INR monitoring or subcutaneous administration. Direct oral anticoagulants are promising due to their convenience and effectiveness in preventing VTE in other settings. They have not been extensively studied in myeloma therapy.Our baseline audit of 82 consecutive myeloma patients treated with IMiD-containing regimens and receiving thromboprohylaxis with aspirin had VTE rates of 11%. Of 31 patients treated with heparins 6.5% had VTE. These rates are consistent with data in the literature. Apixaban is cheaper than LMWH therapy in our centre.In November 2014 our policy was changed such that apixaban became standard thromboprophylaxis; the effect of this change is reported here.AimAssess the safety and efficacy of apixaban as thromboprophylaxis in patients with multiple myeloma undergoing first line therapy with IMID-containing regimens.MethodConsecutively presenting patients between 1st November 2014 and 31st December 2016 with multiple myeloma undergoing first-line therapy with IMiD-containing regimens were included in this retrospective study. All patients received apixaban 2.5mg twice daily for the first 4 months of therapy or until treatment cessation. Patients with severe renal failure (CrCl <15ml/min) or thrombocytopenia <50x10^9/L received alternative anticoagulants and were excluded from this audit. Patients already on warfarin continued on warfarin and were excluded. The primary outcome was the occurrence of arterial or venous thromboembolism. We also recorded incidence of clinically significant bleeding episodes.Results70patients were identified. 45 (64%) were male, the median age was 66 years, range 43-86. Previous thrombosis: 2 PE, 1 stroke, 1 TIA, 3 myocardial infarction. Treatment (n): Cyclophosphamide-Thalidomide-Dexamethasone (19), Bortezomib-Thalidomide-Dexamethasone (27), Lenalidomide-Dexamethasone (3), Carfilzomib-Cyclophosphamide-Lenalidomide-Dexamethasone (8), Melphalan-Prednisolone-Thalidomide (n=9), Lenalidomide-Cyclophosphamide-Dexamethasone (4).There were no DVTs or PEs within 6 months of treatment initiation. Two patients (2.9%) had arterial thrombosis. One patient had a non-haemorrhagic stroke at day 19 with no identified embolic source and she had no cardiovascular comorbidities. One patient had a non-ST elevation myocardial infarction at day 23 with no previous diagnosis of ischaemic heart disease. He had stopped both thalidomide and apixaban 21 days previously due to drug-induced rash. One patient (1.4%) had major bleeding. He had melaena during his 4th cycle of MPT that resolved on apixaban cessation. His platelet count had dropped to 21x10^9/L during this episode. He required hospital admission for blood transfusion, but no bleeding point was identified at endoscopy.Conclusion - We studied the use of apixaban for preventing IMiD-induced thrombosis in front line myeloma therapy. Rates of thrombosis appear to be very low with no cases of VTE identified and only 2 cases of arterial thrombosis. There was one episode of major bleeding in a patient with coexistent thrombocytopenia. These toxicity rates compare favourably to historical and published data with other anticoagulants. The drug is suitable for ambulatory treatment even in frail patients, and avoids the logistical and acceptability problems of subcutaneous injection of LMWH. Apixaban appears to be an attractive and safe option for thromboprophylaxis in this setting. DisclosuresNo relevant conflicts of interest to declare.