RHEDAR study: Determination of the risk of gastrointestinal hemorrhage in treatment with dabigatran, acenocoumarol and rivaroxaban

Abstract

Background and Aim: Atrial fibrillation is a major cause of death and disability due to stroke. Vitamin K antagonist drugs are effective for prevention, but they have a narrow therapeutic range and multiple pharmacological interactions. In recent years, new therapeutic alternatives have been searched to minimize complications. The main objective is to evaluate the risk of gastrointestinal bleeding in anticoagulated patients and compare the classic treatment with new anticoagulants. Methods: We conducted a retrospective cohort study to determine the risk of gastrointestinal bleeding in patients treated with acenocoumarol/dabigatran/rivaroxaban, between 2012 and 2016. We compared the classic with the new anticoagulant group, and a multivariate logistic regression analysis was used to determinate the risk factors of gastrointestinal bleeding. Results: A total of 1213 patients were selected, 52.7% male patients, a mean age of 72.6 years old (± 14.563). 73.6% had atrial fibrilation. 14.5% of patients used acetylsalicylic acid, and 4% clopidogrel. 67.2% had a high-risk CHADS-2 Score, and 36.9% a high-risk HAS-BLED Score. We determined a 5.6% (68) of gastrointestinal bleeding, without differences according to anticoagulant used. The multivariate model showed a greater risk for digestive hemorrhage in patients with a previous hemorrhagic event (odds ratio [OR] = 2.422 95% confidence interval [CI]: 1.101-5.327) and the concomitant therapy with clopidogrel (OR = 2.373 95% CI: 0.996-5.652). Conclusions: No differences were found in the risk of gastrointestinal bleeding between the different anticoagulants. A previous gastrointestinal bleeding were considered independent risk factor. The HAS-BLED score should be taken into account to make clinical decisions about to prescribe anticoagulant treatment.

Risk factors for anticoagulant-associated gastrointestinal hemorrhage: a systematic review and meta-analysis

“…Supplementary Table 1 describes the characteristics of the included studies reporting on the outcomes of GIB. Thirty-three studies were risk factor studies [ 19 – 50 , 51 ]. One study was a prediction model development study [ 52 ].…”

“…One study was a prediction model development study [ 52 ]. Twnety-seven studies were cohorts [ 19 – 21 , 23 – 25 , 27 – 29 , 31 , 34 , 36 – 49 , 51 , 52 ]: 1 of which was prospective cohort [ 40 ], 26 of which were retrospective cohorts [ 19 – 21 , 23 – 25 , 27 – 29 , 31 , 34 , 36 – 39 , 41 – 49 , 51 , 52 ]. Two studies were case-control studies [ 26 , 32 ], 5 were randomized controlled trials (RCTs) [ 22 , 30 , 33 , 35 , 50 ].…”

“…Two studies were case-control studies [ 26 , 32 ], 5 were randomized controlled trials (RCTs) [ 22 , 30 , 33 , 35 , 50 ]. Among the 34 studies, the populations of 23 studies were only stroke patients [ 19 – 22 , 25 , 27 – 37 , 39 – 41 , 43 , 44 , 47 , 50 ], the composition of the population indications in the remaining 11 studies included atrial fibrillation, venous thromboembolism, pulmonary embolism, deep vein embolism, and stroke [ 23 , 24 , 26 , 38 , 42 , 45 , 46 , 48 , 49 ]. Most patients were between 50 and 80 years old, and most were male.…”

“…The risk of bias was serious across all identified studies, each presenting risk of bias in at least 1 domain or item ( Supplementary Table 2 ). Among the 34 included studies, 26 were retrospective, which may have introduced classification bias [ 19 – 21 , 23 – 25 , 27 – 29 , 31 , 34 , 36 – 49 , 51 , 52 ]. We detected evidence of publication bias through visual assessment of asymmetry of the funnel plot for each pooled predictor in those that included at least 10 studies ( Supplementary Table 2 ).…”

“…We found moderate-certainty evidence that there is probably an association between risk of GIB and older age (OR, 1.95; 95% CI, 1.36–2.79) [ 19 , 23 , 24 , 28 , 33 , 36 , 45 , 47 ], age growth (age per year increase; OR, 1.03; 95% CI, 1.01–1.06; age increase per five years; OR, 1.11; 95% CI, 1.06–1.17) [ 40 , 50 , 51 ], and obesity (weight > 120 kg; OR, 1.44; 95% CI, 1.01–2.05) [ 25 ]. We found low-certainty evidence that there may be little to no association between risk of GIB and sex (male vs. female; OR, 0.95; 95% CI, 0.72–1.26) [ 20 , 26 , 28 , 36 , 39 , 40 , 47 ].…”