Cost-effectiveness modelling of novel oral anticoagulants incorporating real-world elderly patients with atrial fibrillation.

BACKGROUND: Novel oral anticoagulants (NOACs) expand the treatment options for patients with atrial fibrillation (AF). Their benefits need to be weighed against the risk-benefit ratio in real-world elderly patients, prompting this cost-effectiveness study of NOACs (apixaban, dabigatran, edoxaban and rivaroxaban), warfarin and aspirin for stroke prevention in AF. METHODS: Applying effectiveness estimates from a network meta-analysis involving over 800,000 patients from randomised controlled trials and observation studies, our Markov model projected cost and health outcomes for a cohort of 65-year-old AF patients over a life-time. We performed subgroup analysis stratified by age (65-74 and ≥75years), with further analysis limited to observational studies involving dabigatran and rivaroxaban. RESULTS: Compared to warfarin, NOACs (except dabigatran 110) were associated with incremental cost-effectiveness ratios ranging from USD 24,476 to USD 41,448 that were within cost-effectiveness threshold of USD 49,700 (one gross domestic product per capita in Singapore in 2015). Aspirin regimens were dominated. In elderly aged ≥75years, cost effectiveness of NOACs (except apixaban) decreased, owing to worsened performance in safety profile. Analysis limited to observational studies revealed that dabigatran 150 and rivaroxaban were not cost-effective, reflecting increased bleeding risks in non-controlled settings. Threshold analyses revealed that apixaban was no longer cost-effective at two to three times higher bleeding risk. CONCLUSIONS: Whilst NOACs are cost-effective in the younger elderly compared to warfarin, their benefits appear to be offset by worsened risk profile in older elderly, especially in non-controlled settings. Decisions on appropriate AF treatment should balance treatment-related benefits, risks, and patient preference.

Clinical and Safety Outcomes of Oral Antithrombotics for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Novel oral anticoagulants (NOACs) expanded the options for stroke prevention in atrial fibrillation (AF). Earlier studies comparing their relative effectiveness and safety typically do not incorporate age-related differences or postmarketing studies. This study aimed to summarize and compare clinical and safety outcomes of oral antithrombotics for stroke prevention in AF in younger (65-74 years) and older (≥75 years) elderly. METHODS: We searched PubMed, Embase, and The Cochrane Library from inception through May 1, 2015, for randomized and nonrandomized studies comparing NOACs, warfarin, and aspirin in elderly with AF. Stroke and systemic embolism (SSE) and major bleeding (MB) are the main outcomes. We also studied secondary outcomes of ischemic stroke, all-cause mortality, intracranial bleeding, and gastrointestinal bleeding. RESULTS: Of 5255 publications identified, 25 randomized controlled trials and 24 nonrandomized studies of 897,748 patients were included. NOACs reduced the risk of SSE compared with warfarin (rate ratios [RRs] range from 0.78-0.82). Relative to SSE, NOACs demonstrated a smaller benefit for ischemic stroke (dabigatran 110 mg, RR 1.08; edoxaban, 1.00; apixaban, 0.99). On the contrary, aspirin was associated with a significantly higher risk of SSE, ischemic stroke, and mortality than warfarin or NOACs (RR > 1), particularly in older elderly. Regarding safety, medium-dose aspirin (100-300 mg daily) and aspirin/clopidogrel combination showed an increased risk of MB compared with warfarin (RR 1.17 and 1.15, respectively), as per dabigatran 150 mg and rivaroxaban in older elderly (RR 1.17 and 1.12, respectively). Among the NOACs, dabigatran 150 mg conferred greater gastrointestinal bleeding risk compared with warfarin (RR 1.51), whereas rivaroxaban (RR 0.73) demonstrated less benefit of reduced intracranial bleeding than other NOACs (RRs range 0.39-0.46). CONCLUSIONS: Lower rates of SSE and intracranial bleeding were observed with the NOACs compared with warfarin. Dabigatran 150 mg and rivaroxaban were associated with higher rates of MB in older elderly.