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ObjectivesFor the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA.Patients and methodsIn 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS).ResultsThe primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed.ConclusionsA multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding.Trial registration numberNCT01431456.

Background: Elderly patients with multiple morbidities and polypharmacy are at an increased risk of adverse drug events (ADEs). Appropriate prescribing, preserving the balance between drug effectiveness and safety, and treatment adherence may prevent these ADEs. In this study, we investigated which drug properties, such as effectiveness, safety, clinical experience and convenience, are relevant to the choice of medicine most appropriate for frail elderly patients. Objectives: The primary aim of this study was to develop a set of criteria to assist in the selection of the most appropriate drug within a drug class for the treatment of frail elderly patients. A secondary goal was to test the usefulness of the set of criteria in the prescription of antipsychotics for delirium and behavioural and psychological symptoms of dementia (BPSD). Methods: Thirty-one criteria potentially relevant to the choice of appropriate drugs for frail elderly patients were selected on the basis of a literature search in MEDLINE (1966–2008), EMBASE (1947–2008) and the Cochrane Library (1993–2008). This list was reviewed by 46 experts (24 physicians, 22 pharmacists), who scored each item for relevance in clinical practice on a scale from 1 to 10 (where 1 is not important and 10 is very important). By consensus, the authors selected the most relevant criteria for the final set of criteria. The usefulness of the final set of criteria was assessed with regard to the prescription of antipsychotics for delirium and BPSD. Results: The final set of 23 items consisted of 3 items on effectiveness, 14 on safety, including pharmacokinetic and pharmacodynamic criteria, 3 on clinical experience and 3 on convenience. Assessment using these criteria of the appropriateness of antipsychotics prescribed for delirium and BPSD revealed that certain drugs should be prescribed with caution to patients with Parkinson’s disease and Lewy body dementia. Conclusions: The criteria identified in this study, selected on the basis of a literature review and clinical expert opinion, represent a promising approach for determining the appropriateness of a drug for use in frail elderly individuals relative to alternative drugs for the same indication or from the same class.

Introduction Two novel agents, dabigatran and rivaroxaban, recently gained market authorisation for prevention of venous thromboembolism (VTE) after hip and knee arthroplasty. However, safety data of the new oral anticoagulants with a long-term use of 42 days are not available for total knee arthroplasty (TKA). Furthermore, there are no clinical trials comparing dabigatran and/or rivaroxaban with nadroparin, which is used in most Dutch departments of orthopaedic surgery. Our aim is to compare the 42-day use of dabigatran and rivaroxaban versus nadroparin after TKA in a clinical explorative pilot study by assessing the incidence of major bleeding and clinically relevant non-major bleeding using a standardised model of bleeding definitions. Methods and analysis A randomised open-label pilot study was conducted. Patients ≥18 years and weighing more than 40 kg who were scheduled for a primary elective TKA were included. Patients were randomly assigned to three groups. Patients took either a daily oral dose of dabigatran etexilate 220 mg (n=50), 10 mg of oral rivaroxaban (n=50) or subcutaneous nadroparin 0.3 ml (n=50) for 42 days. The primary safety outcome measure was the incidence of bleeding events. Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines. The secondary measures of this study were the occurrence of VTE, time until the bleeding event, compliance, duration of hospital stay, rehospitalisation, outpatient clinic visits and interventions following complications. Additionally, coagulation monitoring, knee flexion range of motion and Knee injury and Osteoarthritis Outcome Score were evaluated. Dissemination The results of this trial provided insight into the validity of design for an adequately powered multicentre study investigating the safety of the new oral anticoagulants compared with nadroparin, an anticoagulant applied for prevention of VTE after knee arthroplasty in the Dutch situation. Trial registration number ClinicalTrials.gov: NCT01431456.