Novel anticoagulants for stroke prevention in atrial fibrillation: a systematic review of cost-effectiveness models

Abstract

Objective: To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF).

Patients and methods: We searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF.

Results: Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results.

Conclusions: Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.

Conflict of interest statement

Competing Interests: This study received funding from Janssen Pharmaceuticals. Dr. Coleman is a member of the Janssen Pharmaceuticals advisory board and speaker’s bureau for Xarelto®. Rivaroxaban is a Janssen Pharmaceuticals product. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Results of Literature Search.

Figure 2. Proportion of Reported Incremental Cost-Effectiveness Ratios Below Reported Willingness-to-Pay Threshold.

*Includes results of dabigatran compared to “real-world prescribing”, “trial-like” warfarin control and genotype-guided warfarin †Includes results of dabigatran compared to “trial-like” warfarin control and genotype-guided warfarin.