A Prospective, Randomized, Open-Label Study to Evaluate Two Management Strategies for Gastrointestinal Symptoms in Patients Newly on Treatment with Dabigatran

Daniel O'Dea, Jacqueline Whetteckey, Naitee Ting, Daniel O'Dea, Jacqueline Whetteckey, Naitee Ting

Abstract

Introduction: In the pivotal RE-LY trial, dabigatran etexilate (DE) at the dose of 150-mg twice daily (BID), significantly reduced total stroke and ischemic stroke compared with warfarin in patients with non-valvular atrial fibrillation (NVAF), while the 110-mg BID dose had efficacy equivalent to warfarin, and major bleeds were significantly reduced. Both DE regimens were generally well tolerated; however, approximately 4% of the patients discontinued treatment with DE due to gastrointestinal (GI) discomfort.

Methods: Clinical trial NCT01493557 was a multicenter, randomized, active control, open-label study to assess the efficacy of two simple GI symptom (GIS) management strategies in DE-treated patients who developed GIS: (1) concurrent treatment with the proton pump inhibitor pantoprazole (DE-P), or (2) ingestion of DE after a meal (DE-M). Patients were initially randomized to either GIS management strategy. If the first did not resolve their GIS, patients had the option to "add on" the alternative strategy.

Results: A total of 1067 patients with NVAF received DE therapy BID for 3 months (United States, 150-mg or 75-mg; Canada, 150-mg or 110-mg). Of these, 117 (11%) patients reported GIS and were randomized to one of two GIS management strategies. At 4 weeks, a significantly higher rate of complete or partial effectiveness was observed in patients on DE-P than in those receiving DE-M, [50/58 (86.2%) versus 40/59 (67.8%), respectively; p = 0.0273]. Patients with ongoing GIS were asked to "add on" the alternate strategy for an additional 4 weeks. Overall, 92/117 (78.6%) of randomized patients experienced complete or partial effectiveness using either the initial strategy or a combination of the two strategies: DE-P, 47 (81.0%); and DE-M, 45 (76.3%, no significant difference) (by initial strategy).

Conclusion: The majority of patients enrolled either did not experience GIS at all, or their GIS resolved using either one individually, or a combination of the two strategies described.

Trial registration: http://www.ClinicalTrials.gov identifier: NCT01493557.

Keywords: Dabigatran; Dyspepsia; Gastrointestinal symptoms; Pantoprazole.

Figures

Fig. 1
Fig. 1
GIS trial design
Fig. 2
Fig. 2
Patient outflow

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