Effect of gastroprotective agents on upper gastrointestinal bleeding in patients receiving direct oral anticoagulants

Scand J Gastroenterol. 2018 Dec;53(12):1490-1495. doi: 10.1080/00365521.2018.1541478. Epub 2018 Dec 3.

Abstract

Objectives: Direct oral anticoagulants (DOACs) are effective in the prevention and treatment of thromboembolism; however, they are associated with upper gastrointestinal bleeding (UGIB). In this study, we evaluated the efficacy of gastroprotective agents (GPAs) in reducing the risk of UGIB in patients receiving DOACs.

Methods: We retrospectively reviewed the medical records of 2076 patients who received DOACs for the prevention or treatment of thromboembolic events between January 2008 and July 2016. A cumulative incidence analysis using the Kaplan-Meier method was performed to determine the rate of UGIB and its association with GPAs administration.

Results: Of the 2076 patients, 360 received GPAs. Over the follow-up period (1160 person-years), one patient in the GPA group (0.7 per 100 person-years) and 29 patients in the non-GPA group (2.8 per 100 person-years) developed UGIB (p = .189). In the multivariate analysis, UGIB was associated with older age (hazard ratio (HR), 1.041; p = .048), a history of peptic ulcer or UGIB (HR, 5.931; p < .001), and concomitant use of antiplatelet agents (HR, 3.121; p = .014). GPAs administration did not reduce the risk of UGIB (p = .289). However, based on the subgroup analysis of 225 patients with concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB, the GPA group (0 per 100 person-years) showed reduced incidence of UGIB compared with the non-GPA group (11.3 per 100 person-years) (p = .065).

Conclusions: The prophylactic use of GPAs could reduce the risk of UGIB in patients receiving DOACs who have risk factors, such as concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB.

Keywords: Novel oral anticoagulants; histamine type 2 receptor antagonists; prophylaxis; proton pump inhibitors; upper gastrointestinal bleeding.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology*
  • Gastrointestinal Hemorrhage / prevention & control*
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptic Ulcer / chemically induced
  • Peptic Ulcer / complications
  • Proportional Hazards Models
  • Proton Pump Inhibitors / therapeutic use*
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Thromboembolism / drug therapy
  • Thromboembolism / prevention & control
  • Young Adult

Substances

  • Anticoagulants
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors