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Published: March 2013

Dabigatran - New Contraindication

Prescriber Update 34(1):2
March 2013

Pradaxa (dabigatran etexilate) is now contraindicated in patients with prosthetic heart valves.

The safety and efficacy of Pradaxa in patients with prosthetic heart valves were evaluated in the European RE-ALIGN trial1. This phase II study was terminated early as patients taking Pradaxa experienced significantly more thromboembolic events (valve thrombosis, stroke, and myocardial infarction) and major bleeding events than patients taking warfarin (Table 1). In this study, 160 patients were treated with Pradaxa (dose range: 150mg twice daily to 300mg twice daily) and 89 were treated with warfarin (dose adjusted to therapeutic effect).

Table 1: Patients in the RE-ALIGN study with thromboembolic and/or bleeding events, as of 10 December 20122
  Pradaxa (n=160) Warfarin (n=89)
Death 1 (0.6%) 2 (2.2%)
Stroke 8 (5.0%) 0 (0%)
Systemic embolism event (SEE) 0 0
Transient ischemic attack (TIA) 2 (1.3%) 2 (2.2%)
Valve thrombosis (VT) 4 (2.5%) 0
Myocardial infarction (MI) 3 (1.9%) 0
Composite of events:
16 (10.0%) 4 (4.5%)
Major bleeding 6 (3.8%) 1 (1.1%)
Major bleeding in pericardial location 5 (3.1%) 0
Any bleeding 36 (22.5%) 12 (13.5%)

To date, CARM have received five adverse reaction reports of dabigatran use in patients with prosthetic heart valves. Of the five reports, there were three thromboembolic events, one possible bleed and one unrelated event.

The New Zealand data sheet has been updated to include this new contraindication3. There have been no changes to the approved indications (that is, for use to prevent thrombosis after major orthopaedic surgery and for patients with non-valvular atrial fibrillation).

  1. Van de Werf F, Brueckmann M, Connolly SJ, et al. 2012. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). American Heart Journal 163: 931-7 e1.
  2. Food and Drug Administration. 2012. Pradaxa (dabigatran etexilate mesylate) should not be used in patients with mechanical prosthetic heart valves. FDA Drug Safety Communication 19 December 2012 (accessed 7 February 2013).
  3. Boehringer Ingelheim (NZ) Limited. 2012. Pradaxa data sheet 21 December 2012. URL: (accessed 14 February 2013).


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