Berberine spirin monotherapy, and no treatment. Patients receiving warfarin were assumed to maintain a level of INR control consistent with that observed in RE LY, which compares favourably with that observed in routine UK practice.18 19 Therefore it can be regarded that dabigatran was compared to trial like warfarin in the UK setting. Model structure The model followed patients with AF through the natural course of disease in 3 month cycles, included all relevant clinical outcomes and incorporated health states stratified by treatment history, stroke history and disability level.16 Major clinical events included in the model were primary and recurrent strokes and haemorrhagic, SE, transient ischaemic attack, acute myocardial infarction, ICH excluding HS, major extracranial haemorrhage, minor bleeding and death. Each event was defined in accordance with clopidogrel 120202-66-6 clinical definitions from the RE LY trial.12 13 IS, HS and ICH could be disabling or non disabling, with disabling events resulting in permanent functional deficits taurine 107-35-7 characterised by modified Rankin Score for IS, and by Glasgow Outcomes Scale for ICH and HS. All haemorrhagic events could result in discontinuation of current treatment.
Patients could also discontinue for other, possibly non clinical, reasons. When patients discontinued anticoagulant therapy, they switched to aspirin. Patients who discontinued aspirin received no further antithrombotic therapy. A model structure outline is presented in figure 1. Model outcomes included number of clinical events normalised to 100 patient years, QALYs, total and disaggregated costs and incremental cost per QALY gained. QALYs are computed by multiplying the time a patient survives by a weight representing their quality of life during that time, with weights ranging from 1 to 0. Because the consequences of stroke and haemorrhage could be life long, the model assumed a fingolimod lifetime horizon in the base case. The model assumed patients not discontinuing remain adherent to antithrombotic treatment, and the relative treatment effect remained constant over time. Patients discontinuing treatment received no further clinical benefit.
Future costs and outcomes were discounted at 3.5% per annum. The intention was that all aspects of the analysis were conducted in line with the principles of the National Institute for Health and Clinical Excellence Reference Case wherever possible.20 The model implementation used Microsoft Excel.Data sources The primary source of clinical input data was the RE LY trial,12 13 and an adaptation of a published mixed treatment comparison based on a network meta analysis to synthesise efficacy and safety data of treatments frequently used in prevention of stroke and SE in patients with AF.Baseline characteristics of the patient population in the model matched those randomised to the RE LY trial. Patients were diagnosed with AF plus at least one additional risk factor for stroke or SE, as defined by the CHADS2 risk stratification scheme, or impaired left ventricular ejection fraction. Patients had CHADS2 scores ranging from 0 to 6. The mean CHADS2 score in RE LY was 2.1, with roughly two thirds of patients having a CHADS2 score of 2 or higher. At baseline, approximately 20% of patients had a history of previous stroke or TIA.