092P Queen Elizabeth II Conference Centre London
Pharmacology 2014

 

 

Prevention of Dabigatran Related Gastrointestinal Bleeding With Acid Suppressive Agents

ICK Wong1, EWY Chan1, WCY Lau1, WK Leung1, MTC Mok2, Y He1, TSM Tong1. 1The University of Hong Kong, Hong Kong, Hong Kong, 2Geelong Hospital and Deakin University, Victoria, Australia

Dabigatran, a direct thrombin inhibitor, is the first new oral anticoagulant approved for use as an alternative to warfarin. Despite its convenience and superiority over warfarin, an increased risk of gastrointestinal bleeding (GIB) of dabigatran has been continually reported in randomized controlled trials. A number of case reports revealed early onsets of GIB occurring within the first month of starting dabigatran. The aim of this study was to determine the actual risk of early GIB, risk factors and the effect of acid-suppressive agents, including proton pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), in the prevention of dabigatran-associated GIB in the real-world practice.

Patients newly prescribed dabigatran between 2010 and 2013 were identified in the Hong Kong Clinical Data Analysis and Reporting System (CDARS), a population-wide database managed by the Hong Kong Hospital Authority whose services are accessible to over seven million people. Poisson regression was used to assess the risk of GIB within 30 days after the first dose of dabigatran in terms of incidence rate ratio (IRR), controlled for patient characteristics and concurrent medications.

Among the 5041 patients newly prescribed dabigatran, 56 (1.1%) developed GIB during the 30-day follow-up. A higher risk of GIB was observed in patients aged ≥75 years or with a history of peptic ulcers/GIB (Table 1). Concomitant use of acid-suppressive agents was associated with a reduced risk of GIB (IRR, 0.39; 95% CI, 0.22-0.68). The findings were consistent in both new oral anticoagulation starters and switchers. The risk reduction by acid-suppressive agents was significant only in patients with prior history of peptic ulcers or GIB. In conclusion, this study showed that concomitant use of acid-suppressive agents was associated with reduced risk of GIB in patients on dabigatran.

Table 1 Results of Poisson regression on GIB within the first 30 days of starting dabigatran

n Incidence rate ratios (95% CI)
No. of GIB / Total no. of patients 56/5041 -
Total no. of patient years 409 -
Age ≥75 2368 3.89 (2.06, 7.35)*
Sex (Male) 2412 1.06 (0.62, 1.81)
Baseline conditions
Prior ischemic stroke/transient ischemic attack/systemic embolism 1413 1.13 (0.64, 2.00)
Renal disease 215 0.73 (0.18, 3.01)
History of peptic ulcer/GIB 700 3.08 (1.73, 5.48)*
Concurrent Medication
Aspirin 1294 1.51 (0.83, 2.76)
Clopidogrel 127 -
Acid-suppressive agents 3064 0.39 (0.22, 0.68)*
Non-steroidal anti-inflammatory drugs 285 1.90 (0.57, 6.27)
Selective serotonin reuptake inhibitors 135 0.66 (0.09, 4.82)

*p<0.05.