Dabigatran Etexilate for the Prevention of Venous Thromboembolism in Patients Undergoing Elective Hip or Knee Surgery

The National Institute for Health and Clinical Excellence (NICE) invited Boehringer Ingelheim GmbH, the manufacturer of dabigatran etexilate (DBG), to submit evidence on the clinical and cost effectiveness of this drug for the primary prevention of venous thromboembolism (VTE) in adult patients who have undergone total hip replacement (THR) or total knee replacement (TKR) surgery, as part of NICE’s single technology appraisal process. The comparators were enoxaparin and fondaparinux, as identified in the scope issued by NICE. The School of Health and Related Research at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions.

Clinical-effectiveness evidence for DBG versus enoxaparin was derived from two randomized, double-blind, noninferiority trials, one for THR and the other for TKR. Clinical-effectiveness evidence for DBG versus fondaparinux was taken from a mixed treatment comparison (MTC) and from one study. The results presented show that DBG at the licensed dose of 220mg and 150mg once daily was noninferior to enoxaparin (40mg once daily) in terms of the primary efficacy outcome of total VTE and all-cause mortality. In the MTC, fondaparinux was found to be more effective than DBG; the level of statistical significance was not reported.

The manufacturer’s cost-effectiveness model estimated that at a dose of 220mg once a day, DBG dominated enoxaparin in both THR and TKR. At a dose of 150mg daily, DBG dominated enoxaparin in THR, while enoxaparin dominated DBG in TKR. At a dose of 220mg daily, DBG was less cost effective than fondaparinux in THR. The cost per QALY gained for fondaparinux versus DBG was £11111 (year 2008 values). At a dose of 150mg daily, DBG was less cost effective than fondaparinux in THR. The cost per QALY gained for fondaparinux versus DBG was £6857 (year 2008 values). In TKR, both DBG doses were dominated by fondaparinux.

There was some evidence that DBG was more cost effective than enoxaparin; however, these results were based on only one trial each in THR and TKR. Fondaparinux appeared to be more cost effective than DBG; however, this was based on indirect comparisons. NICE concluded that although there was uncertainty in the evidence base, DBG was very likely to be of equivalent clinical and cost effectiveness to enoxaparin or fondaparinux in the prevention of VTE. The NICE Appraisal Committee (AC) acknowledged that oral administration of DBG, without the need for monitoring, would reduce administration costs and that it may support adherence to treatment. Therefore, the AC concluded that DBG should be recommended as an option in the circumstances in which enoxaparin (or fondaparinux as an alternative) may be offered.