Letters to the Editor

Abstract

LETTERS TO THE EDITOR Ximelagatran cost effectiveness for stroke prevention in atrial fibrillationTo the Editor, In their recent article Valiya et al. concluded that ximelagatran appears to be cost effective in a small group of patients at high risk of bleeding. 1 We believe that this conclusion is not justified based on the findings published in the article. The analysis was based primarily on the results of the open-label SPORTIF III study in which ximelagatran was compared to warfarin for the prevention of thromboembolic stroke associated with atrial fibrillation. 2In this study, both the rate of ischaemic stroke and major bleeding were not significantly different between the anticoagulants. In their analysis, Valiya et al. use a base-case rate of major bleeding of 1.3 events per annum for each drug. We find it baffling that the authors then suggest that ximelagatran would be superior in patients who cannot tolerate warfarin.Ximelagatran has never been studied in patients who have suffered a major bleed or who have other problems while receiving warfarin-these patients were excluded from the trials. Neither head-to-head trial comparing the drugs demonstrated a significant reduction in major bleeding. 2,3Indeed, if the closed-label SPORTIF V trial is given precedence, warfarin was nearly statistically significantly superior at preventing stroke. If the major bleeding rates are similar, it is presumptuous to suggest that ximelagatran would be safer in patients suffering a warfarin-related bleed. Indeed, the authors could have considered the opposite scenario as well. The worstcase major bleeding incidence for warfarin used in the analysis is almost double the rate noted in combined analysis of the SPORTIF trials. 4 The authors did not consider the costs attributable to adverse events associated with ximelagatran, namely monitoring of alanine transaminase (ALT), hepatic failure and cessation of treatment in those with sustained elevations of ALT. This data is available from SPORTIF III, SPORTIF V (published in abstract form in 2004) and the US FDA, published when approval for ximelagatran was not granted because of a lack of safety data and concern about hepatic adverse events. 2,3,5 This data was available prior to submission of the article by Valiya et al. (January 2005). Indeed, AstraZeneca recently removed ximelagatran from the global market due to these safety concerns. Compared to a similar analysis, the cost of each INR test in the Valiya et al. analysis is higher and the cost attributed to a major bleed significantly higher, effectively resulting in a lower estimate of the incremental cost-effectiveness ratio of ximelagatran compared to warfarin. 4 While warfarin is not a perfect drug, there is scope to improve its management. In one analysis of major bleeding in the elderly, 17 of 18 events were considered preventable by either avoiding overanticoagulation, or drugs that added to the bleeding risk. 6 We believe the following should have been the primary conclusion of the analysis: ximelagat...