ALBERT

Description: Introduction: Current guidelines recommend low-molecular-weight heparins (LMWH) over Vitamin K Antagonists (VKA) or Non-Vitamin K Antagonist Oral Anticoagulants (NOAC) for the treatment of cancer-associated venous thromboembolism (CAT), but also highlight that ultimately the choice of anticoagulant depends on patient-specific factors such as patient preferences, which is important for the acceptance of the treatment and, thus, for adherence and persistence. So far, little is known about the specific preferences of patients with CAT with respect to anticoagulation therapy. More specifically, the impact of dosing regimen, convenience and costs on patient preferences in CAT is poorly understood. Therefore, the objective of this discrete choice experiment (DCE) was to elucidate patient preferences regarding anticoagulation convenience attributes. Methods: Adult patients with active cancer who experienced a CAT event and for whom the decision was made to start a treatment with rivaroxaban after being treated with the standard of care anticoagulation (LMWH/VKA) for at least four weeks were included in a multinational, observational, single-arm study (COSIMO). As part of this study, a DCE was presented to the participants, who were asked to decide between complete hypothetical treatment options based on a combination of different attributes, regardless of efficacy or safety. The following attributes were preselected in a face-to-face discussion with three focus patients and in-depth interviews with four additional patients: route of administration (injection / tablet),frequency of intake (once / twice daily),need of regular controls of the International Normalized Ratio (INR) at least every 3-4 weeks (yes/no),interactions with food/alcohol (yes/no). Additionally, distance to treating physician (1 km vs. 20 km) was included as neutral comparator to express patients' overall utility in terms of a comprehensible unit. The relative importance of treatment attributes in terms of distances were calculated based on ratios between the utility estimates for each attribute. A fractional factorial design was generated resulting in nine hypothetical choice sets, supplemented by a test choice set to assess the consistency of a patient's responses. DCE data was collected by semi-structured telephone interviews, performed between week 4 and week 12 after enrollment of patients in the study and start of rivaroxaban. For each patient participating in the DCE interview, a written informed consent was obtained. Patient preferences were analyzed based on a conditional logit regression model. Results: Overall, 163 patients were included (Europe: 119; Canada: 41; Australia: 3), mean age 63.7 years, 49.1% were females and diagnosed with cancer for on average 22.4 months. Most patients in the COSIMO study changed to rivaroxaban from LMWH (〉 95.0 %). The median time from diagnosis of index CAT event to conduct of DCE was 150 days (IQR 88-229). Patients strongly preferred oral administration compared to self-injections and drugs that can be taken irrespective of type of food or alcohol consumption (Figure 1). Furthermore, patients indicated slight preference for a shorter distance to the treating physician and a once daily dosing regimen compared to a twice-daily intake. The attribute "INR controls" showed no significant impact on the treatment decision. In order of patients' preference for their choice of treatment, the route of administration was by far the most important attribute for a patient's choice (73.8% of the overall decision), followed by food interactions (11.8%), the distance to treating physician (7.2%) and the intake frequency (6.5%). Accordingly, the expected utility of patients receiving an oral anticoagulation can be expressed as willingness to travel an additional distance of 192 km to the treating physician in order to avoid an injection. Conclusions Treatment related decision-making of patients with CAT, assuming equal effectiveness and safety of treatments, is predominantly driven by "route of administration", indicating a strong preference for oral intake. Disclosures Picker: Ingress-Health: Employment. Cohen:Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ACI Clinical: Consultancy; GLG: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy; Boston Scientific: Consultancy; AbbVie: Consultancy; Boehringer-Ingelheim: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Aspen: Consultancy, Speakers Bureau; Guidepoint Global: Consultancy; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Leo Pharma: Consultancy; Medscape: Consultancy, Speakers Bureau; McKinsey: Consultancy; Navigant: Consultancy; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy; Temasek Capital: Consultancy; TRN: Consultancy; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism. Maraveyas:Bayer AG: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding. Lee:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Mantovani:Fondazione Charta: Consultancy; Bayer AG: Honoraria; Boehringer Ingelheim: Honoraria, Research Funding; Pfizer: Honoraria; Daiichi Sankyo: Research Funding. De Sanctis:Bayer US LLC: Employment, Equity Ownership. Abdelgawwad:Bayer AG: Employment. Fatoba:Bayer AG: Employment. Bach:Bayer AG: Employment. Wilke:Astra Zeneca: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Pharmerit: Consultancy, Honoraria; Bayer AG: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria.

Description: Background: Heparin-induced thrombocytopenia (HIT) is an immune mediated, pro-thrombotic disorder associated with exposure to heparin and a substantial number of patients develop thrombosis (HITT) in the venous, arterial, or microvascular system. Treatment includes cessation of heparin and starting a non-heparin anticoagulant. Patients with cancer are already at high risk of venous thromboembolism (VTE) as well as recurrent VTE despite anticoagulant therapy and are also at higher risk of bleeding compared with patients without cancer. Consequently, cancer patients may not share similar outcomes as patients without cancer in the setting of HIT. We conducted a single-centre, retrospective study to evaluate baseline characteristics, treatments and outcomes in HIT patients with and without cancer. Methods: Medical records of all patients seen at our tertiary centre between November 1, 2006 and December 31, 2016 who tested positive for HIT antibodies and had a 4T score of 4 or higher were reviewed. Patients with cancer were defined as those who had any evidence of cancer, including myeloproliferative neoplasm (MPN), and/or receiving cancer treatment within 6 months prior to HIT diagnosis. Details of treatments and outcomes were captured up to 6 months after start of HIT treatment. Comparative statistics was performed between the cancer and non-cancer cohorts. Results: We identified 95 patients with confirmed HIT, of whom 39 (41%) had cancer and 41 (43%) had HITT as the index event. The mean age was 65 years (standard deviation 16) and 59% were female. Thirty (77%) cancer patients had at least 3 months of available records and 26 (67%) had at least 6 months, while 37 (66%) non-cancer patients had at least 3 months of available records and 27 (48%) had at least 6 months. Baseline demographics including cancer types are summarized in Table 1. The most common malignancy was polycythemia vera (PV), with those with MPN (7 PV, 2 essential thrombocythemia) representing 23% of the patients with cancer. Cancer patients were more likely to have a history of thromboembolic events prior to index heparin exposure and HIT diagnosis (79.5% vs. 53.6%, p=0.02) than those without cancer. Among patients with HITT, the two groups had similar incidences of pulmonary embolism and/or deep vein thrombosis, although a higher proportion of the non-cancer group had clots in other non-classic locations (32.1% vs. 10.3%, p=0.01) such as splanchnic thrombosis. A variety of non-heparin agents were used, including direct oral anticoagulants (Table 2), with most patients receiving either fondaparinux or argatroban followed by warfarin. The cancer group received fondaparinux more often than the non-cancer group (87.2% vs. 64.3%, p=0.02). In those alive with at least 6 months of follow-up, the median duration of non-heparin anticoagulation was 180 days for both cancer patients and non-cancer patients. During follow-up, 16 (17%) patients had a thrombotic event, 15 (16%) had major bleeding and 11 (12%) died among the 95 patients with HIT. The rates of subsequent thrombosis, bleeding events, and death were similar between the two cohorts over the 6-month follow-up period (Table 3). None of the deaths were from thrombotic or bleeding events but the cause of death for one patient with cancer was unknown. Conclusion: Patient outcomes following a diagnosis of HIT appear similar between patients with and without cancer, with high rates of subsequent thrombosis and major bleeding. Patients with MPN might have a higher risk of HIT. Further studies are warranted to confirm these findings and determine if direct oral anticoagulants might be efficacious and safe in patients with HIT. Disclosures Lee: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. OffLabel Disclosure: Direct oral anticoagulants and fondaparinux were used as non-heparin anticoagulants for the treatment of heparin induced thrombocytopenia.

Description: Background: Patients living with cancer who develop venous thromboembolism (VTE) have a high risk of VTE recurrence, and traditional anticoagulants (low molecular weight heparin [LMWH] or vitamin K antagonists [VKAs]) are associated with significant treatment burdens. Rivaroxaban is a direct oral anticoagulant (DOAC) that may provide a more convenient treatment option for these patients. Methods: The COSIMO study was a multinational, prospective, non-interventional, single-arm cohort study designed to collect real-world data on patient treatment satisfaction and outcomes associated with rivaroxaban treatment following ≥4 weeks of LMWH/VKA therapy for the treatment of acute VTE in patients with active cancer. Here, we report on the secondary objectives, which were to provide descriptive analyses of clinical characteristics and patterns of use of anticoagulant treatment, and to assess the safety and effectiveness of rivaroxaban in this patient population. Results: Overall, 505 patients were enrolled, and the qualifying venous thromboembolic event was deep vein thrombosis (DVT) only in 45.3% of patients, pulmonary embolism (PE) only in 37.2% of patients, DVT with PE in 9.7% of patients, and catheter-associated DVT in 7.5% of patients (Table). The majority of patients had solid tumors (n=449, 88.9%); 56 patients had hematological malignancies. The most common reasons to switch to rivaroxaban were patient preference/quality of life (n=310, 61.4%) and physician decision (n=174, 34.5%). A total of 150 (29.7%) patients were treated with concomitant chemotherapy and 79 (15.6%) received concomitant radiotherapy. Overall, 117 (23.2%) patients discontinued the study: 59 (11.7%) died, 21 (4.2%) withdrew consent, and 17 (3.4%) were lost to follow-up. 80.2% of patients were treated with rivaroxaban for at least 3 months, and most patients (78.6%) received rivaroxaban 20 mg once daily on study entry. Treatment-emergent adverse events (AEs) were reported: 312 (61.8%) patients had an AE (148 [29.3%] serious AEs), and 95 (18.8%) patients had a bleeding event reported, of which 18 (3.6%) patients had an adjudicated major bleeding event. Adjudicated symptomatic and incidental VTE recurrence occurred in 15 (3.0%) and 3 (0.6%) patients, respectively. Adjudicated other site thromboembolic events such as splanchnic or cerebral vein thromboses were symptomatic in 1 (0.2%) patient and incidental in 1 (0.2%) patient. Conclusions: Observed incidence rates of VTE and bleeding events in COSIMO were similar to previous studies of DOACs for VTE treatment in patients with active cancer (Young AM et al. J Clin Oncol 2018;36:2017; Raskob GE et al. N Engl J Med 2018;378:615). Study governance Bayer AG Funding The COSIMO study is funded by Bayer AG and Janssen Pharmaceuticals. Trial protocol number NCT02742623. Registered 19 April 2016. Documented approval from appropriate independent ethics committees/institutional review boards will be obtained for all participating centers prior to study start. Patients were asked to provide signed informed consent forms before joining the study. Few patients have yet completed the study, and so no data are available to share. Acknowledgements Editorial assistance was provided by Kate Weatherall of Chameleon Communications Int. Ltd. with funding from Bayer AG and Janssen Scientific Affairs, LLC. Disclosures Maraveyas: Bristol-Myers Squibb: Honoraria; Bayer AG: Honoraria, Research Funding; Pfizer: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding. Lee:Pfizer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Mantovani:Daiichi Sankyo: Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bayer AG: Honoraria; Fondazione Charta: Consultancy; Pfizer: Honoraria. De Sanctis:Bayer US LLC: Employment, Equity Ownership. Abdelgawwad:Bayer AG: Employment. Fatoba:Bayer AG: Employment. Bach:Bayer AG: Employment. Cohen:Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ACI Clinical: Consultancy; CSL Behring: Consultancy; Aspen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Consultancy, Speakers Bureau; TRN: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Temasek Capital: Consultancy; Boston Scientific: Consultancy; Guidepoint Global: Consultancy; Medscape: Consultancy, Speakers Bureau; McKinsey: Consultancy; Navigant: Consultancy; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Leo Pharma: Consultancy; GLG: Consultancy; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Background Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. Despite therapeutic anticoagulation, the risks of recurrent VTE and major bleeding are approximately 10% and 5%, respectively, during the first 6 months of treatment. Overall mortality ranges from 25% to 40%, depending on the study population. Knowing the case fatality rates of these outcomes is also important for weighing the relative risks and benefits of anticoagulation in patients with cancer-associated VTE but these rates have not been reported previously. Objective To determine the incidence of recurrent VTE and major bleeding events and to calculate the case fatality rates of these outcomes in patients undergoing anticoagulation for cancer-associated VTE. Methods An electronic search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials from January 1980 to May 2018 was performed. English language publications (observational studies and randomized controlled trials [RCTs]) that reported on patients with active cancer and VTE who received anticoagulation with low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC) for at least 3 months were retrieved for review. In addition, a hand search of references of review articles was done to complement the electronic literature search. Studies that provided information on recurrent VTE, major bleeding events, mortality, and causes of death were included in analyses. Retrospective studies and prospective cohorts with fewer than 50 patients were excluded. Two reviewers independently screened for study eligibility and extracted data onto standardized forms. Study outcomes were recurrent VTE, major bleeding and death. Pooled proportions with 95% confidence intervals (CI) were calculated according to anticoagulant treatment and study design. Results The search identified 7327 studies of which 29 studies (15 prospective cohort studies and 14 randomized controlled trials) were included. Data from 8000 cancer patients followed for a total of 4786 patient-years (range 3 to 36 months) were summarized. The rate of recurrent VTE and fatal recurrent VTE were 15.7% (95% CI, 14.4% to 17.1%) and 2.5% (95% CI, 2.0% to 3.0%) per patient-year of follow-up, respectively, with a case fatality rate of 15.8% (95% CI, 12.7% to 18.8%). A sub-analysis revealed case fatality rates for recurrent VTE to be 16.3% (95% CI, 12.2% to 20.4%) for LMWH, 20.4% (95% CI, 14.0% to 26.8%) for VKA, and 10.8% (95% CI, 3.2% to 18.3%) for DOAC therapies. The rate of major bleeding and fatal major bleeding events were 6.4% (95% CI, 5.5% to 7.3%) and 1.2% (95% CI, 0.8% to 1.6%) per patient-year of follow-up, respectively, with a case fatality rate of 12.3% (95% CI, 8.7% to 15.9%). A sub-analysis revealed case fatality rates for major bleeding events to be 14.9% (95% CI, 9.6% to 20.2%), 27.9% (95% CI, 14.5% to 41.3%), and 1.9% (95% CI, 0% to 5.5%) for LMWH, VKA, and DOAC therapies, respectively. Among RCTs, case fatality for recurrent VTE was 17.3% (95% CI, 13.5% to 21.2%) and for major bleeding was 10.8% (95% CI, 3.2% to 18.3%). Among prospective cohort studies, respective case fatality rates were 12.8% (95% CI, 8.0% to 17.5%) and 15.3% (95% CI, 8.6% to 22.0%). Studies were heterogeneous in the duration of follow up and their reporting of the causes of death and definition of fatal PE. Conclusion The incidences of recurrent VTE and major bleed events are high in patients with cancer-associated VTE on anticoagulant therapy. Case fatality from recurrent thrombosis is higher than the case fatality from major bleeding. Differences among various anticoagulants likely reflect patient selection bias and heterogeneity of studies. Disclosures Lee: BMS: Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Servier: Honoraria.

Description: Introduction: The perioperative management of patients who are taking a direct oral anticoagulant (DOAC) for atrial fibrillation (AF) and require an elective surgery/procedure is uncertain. No studies have addressed the timing of perioperative DOAC interruption and resumption, and if perioperative heparin bridging and coagulation function testing are needed. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study hypothesized that a simple, standardized perioperative management strategy, based on DOAC-specific interruption and resumption intervals, that foregoes perioperative heparin bridging and coagulation function testing, is safe for patient care, with associated low rates of major bleeding (1%) and arterial thromboembolism (0.5%). We postulated that this management yields a high proportion of patients (〉90%) with a minimal to no DOAC level at surgery/procedure. Methods: PAUSE is a prospective study with 3 parallel DOAC cohorts of patients with AF taking apixaban, dabigatran or rivaroxaban and requiring anticoagulant interruption for an elective surgery/procedure. Patients were managed using a standardized protocol based on DOAC pharmacokinetic properties, procedure-associated bleeding risk (Appendix 1) and creatinine clearance (CrCl). DOACs were interrupted for 1 day before and after surgery for a low bleed risk surgery and 2 days before and after a high bleed surgery; longer interruption was done in patients on dabigatran with a CrCl