Major bleeding risk associated with oral anticoagulant in real clinical practice. A multicentre 3-year period population-based prospective cohort study

Abstract

Aims: The objective was to compare major bleeding risk of direct oral anticoagulants (DOACs; per type and dose) with vitamin K antagonists (VKAs), irrespective of indication, using real-world data.

Methods: A population-based prospective cohort study, using the French national health data system (SNIIRAM), identified 47 469 adults living within 5 well-defined geographical areas, who were new users of oral anticoagulants in the period 2013-2015: 20 205 VKA users, 19 579 rivaroxaban users, 4225 dabigatran users and 3460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism).

Results: Compared to VKAs, high and low-dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37-0.82 and 0.54, 0.26-1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29-0.58 and 0.41, 0.22-0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding.

Conclusion: There is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.

Trial registration: ClinicalTrials.gov NCT02886533.

Keywords: major bleeding; oral anticoagulant; real-world data.

Conflict of interest statement

There are no competing interests to declare.

© 2020 The British Pharmacological Society.

Figures

FIGURE 1

Study population

FIGURE 2

Association estimates between each major bleeding event, all‐cause mortality, and direct oral anticoagulant (DOAC) compared to vitamin K antagonist (VKA). CI, confidence interval; GI, gastrointestinal; HR, hazard ratio

FIGURE 3

Association between each major bleeding event, all‐cause mortality and direct oral anticoagulant (DOAC) compared to vitamin K antagonist (VKA) for venous thromboembolism or stroke prevention with atrial fibrillation. CI, confidence interval; GI, gastrointestinal; HR, hazard ratio