Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study.
OBJECTIVE
To determine the real world safety of dabigatran or rivaroxaban compared with warfarin in terms of gastrointestinal bleeding.


METHODS
Retrospective cohort study.


METHODS
Large administrative database of commercially insured people in United States from 1 October 2010 through 31 March 2012.


METHODS
Enrollees with a prescription of warfarin, dabigatran, or rivaroxaban between 1 October 2010 and 31 March 2012, who were aged 18 years or older, had continuous enrollment and no oral anticoagulant use during the six months before the entry date, with known age and sex, and with no gastrointestinal bleeding for at least six months before the cohort entry date. The final study sample of 46,163 patients included 4907 using dabigatran, 1649 using rivaroxaban, and 39,607 using warfarin.


METHODS
Time to gastrointestinal bleeding. Hazard ratios were derived from Cox proportional hazard models with propensity score weighting and robust estimates of errors.


RESULTS
Dabigatran users tended to be older (dabigatran v rivaroxaban v warfarin: 62.0 v 57.6 v 57.4 years) and more likely to be male (69% v 49% v 53%). The rate of gastrointestinal bleeding was highest among dabigatran users and lowest among rivaroxaban users (dabigatran v rivaroxaban v warfarin: 9.01 v 3.41 v 7.02 cases per 100 person years). After adjustment for potentially confounding covariates, there was no evidence of a statistically significant difference in the risk of gastrointestinal bleeding between dabigatran and warfarin users (adjusted hazard ratio 1.21, 95% confidence interval 0.96 to 1.53) or between rivaroxaban and warfarin users (0.98, 0.36 to 2.69).


CONCLUSIONS
Although rates of gastrointestinal bleeding seem to be similar in this commercially insured sample of adults in the United States, we cannot rule out as much as a 50% increase in the risk of gastrointestinal bleeding with dabigatran compared with warfarin or a more than twofold higher risk of bleeding with rivaroxaban compared with warfarin.
Department of Health Policy and Management, Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA hchang24@jhmi.edu.
Hsien-Yen
HY
Chang
Department of Epidemiology, Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Meijia
M
Zhou
Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
Wenze
W
Tang
Department of Epidemiology, Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, MD 21205, USA.
G Caleb
GC
Alexander
Department of Epidemiology, Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, MD 21205, USA.
Sonal
S
Singh
D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000453:epidemiology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D000069604:Dabigatran; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects*; D064887:Observational Studies as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D013876:Thiophenes; D015091:beta-Alanine; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran