Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study.

OBJECTIVES: For 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 METHODS: In 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). RESULTS: The 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. CONCLUSIONS: A 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 NUMBER: NCT01431456.

Criteria for drug selection in frail elderly persons.

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.