Impact of new oral anticoagulants on gastrointestinal bleeding in atrial fibrillation: A meta-analysis of interventional trials.
BACKGROUND
New oral anticoagulants represent an alternative to standard therapy with vitamin K antagonists but data regarding gastrointestinal bleeding are still unclear.


OBJECTIVE
To investigate if new oral anticoagulants are associated with an enhanced risk of gastrointestinal bleeding vs warfarin in patients with atrial fibrillation.


METHODS
Meta-analysis of phase three randomized controlled trials to compare the incidence of gastrointestinal bleeding in atrial fibrillation patients treated with new oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) vs warfarin.


RESULTS
Four studies including 71,302 patients were selected. Compared with warfarin, new oral anticoagulants significantly increased gastrointestinal bleeding (RR: 1.23; 95% CI 1.03-1.46; p=0.01). Rivaroxaban (RR: 1.46; 95% CI 1.2-1.8; p<0.001) and high dosages of edoxaban (RR: 1.22; 95% CI 1.01-1.47; p=0.038) and dabigatran (RR: 1.50; 95% CI 1.20-1.88; p<0.001) significantly increased gastrointestinal bleeding while a null effect was detected with apixaban.


CONCLUSIONS
This meta-analysis suggests that rivaroxaban and high dosages of dabigatran and edoxaban should be avoided in patients at high risk of gastrointestinal bleeding.
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: lorenzo.loffredo@uniroma1.it.
Lorenzo
L
Loffredo
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
Ludovica
L
Perri
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
Francesco
F
Violi
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban
Anticoagulants; Atrial fibrillation; Gastrointestinal haemorrhage; Haemorrhage