Antithrombotic stewardship: A multidisciplinary team approach towards improving antithrombotic therapy outcomes during and after hospitalisation

_Introduction:_ Antithrombotic therapy carries high risks for patient safety. Antithrombotics belong to the top 5 medications involved in potentially preventable hospital admissions related to medication. To provide a standard for antithrombotic therapy and stress the importance of providing optimal care to patients on antithrombotic therapy, the Landelijke Standaard Ketenzorg Antistolling (LSKA; Dutch guideline on integrated antithrombotic care) was drafted. However, the mere publication of this guideline does not guarantee its implementation. This may require a multidisciplinary team effort. Therefore, we designed a study aiming to determine the influence of hospital-based antithrombotic stewardship on the effect and safety of antithrombotic therapy outcomes during and after hospitalisation. _Methods and analysis:_ In this study, the effect of the implementation of a multidisciplinary antithrombotic team is compared with usual care using a pre-post study design. The study is performed at the Erasmus University Medical Center Rotterdam and the Reinier de Graaf Hospital Delft. Patients who are or will be treated with antithrombotics are included in the study. We aim to include 1900 patients, 950 in each hospital. Primary outcome is the proportion of patients with a composite end point consisting of ≥1 bleeding or ≥1 thrombotic event from the beginning of antithrombotic therapy (or hospitalisation) until 3 months after hospitalisation. Bleeding is defined according to the International Society of Thrombosis and Haemostasis (ISTH) classification. A thrombotic event is defined as any objectively confirmed arterial or venous thrombosis, including acute myocardial infarction or stroke for arterial thrombosis and deep venous thrombosis or pulmonary embolism or venous thrombosis. An economic evaluation is performed to determine whether the implementation of the multidisciplinary antithrombotic team will be cost-effective. _Ethics and dissemination:_ This protocol was approved by the Medical Ethical Committee of the Erasmus University Medical Center. The findings of the study will be disseminated through peer-reviewed journals and presented at relevant conferences

Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation w

Effect of antithrombotic stewardship on the efficacy and safety of antithrombotic therapy during and after hospitalization

BACKGROUND: Although the benefits of antithrombotic drugs are indisputable to reduce thrombotic events, they carry a high risk of compromising patient safety. No previous studies investigated the implementation and (cost-) effectiveness of a hospital-based multidisciplinary antithrombotic team on bleeding and thrombotic outcomes. The primary aim of this study was to compare the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. METHODS AND FINDINGS: A prospective, multicenter before-after intervention study was conducted in two Dutch hospitals. Adult patients hospitalized between October 2015 and December 2017 treated with anticoagulant therapy were included. The primary aim was to estimate the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. The intervention was the implementation of a multidisciplinary antithrombotic team focusing on education, medication reviews by pharmacists, implementing of local anticoagulant therapy guidelines based on national guidelines, patient counselling and medication reconciliation at admission and discharge. The primary endpoint was analysed using segmented linear regression. We obtained data for 1,886 patients: 941 patients were included in the usual care period and 945 patients in the intervention period. The S-team study showed that implementation of a multidisciplinary antithrombotic team over time significantly reduced the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs (-1.83% (-2.58% to -1.08%) per 2 month period). CONCLUSIONS: This study shows that implementation of a multidisciplinary antithrombotic team over time significantly reduces the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs. TRIAL REGISTRATION: Trialregister.nl NTR4887