Factors Associated With Bleeding Events in Anticoagulated Patients With Afib

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Attending to modifiable risk factors is an important treatment target in patients with atrial fibrillation treated with anticoagulants to reduce thromboembolic and bleeding events.

Risk factors associated with higher thromboembolic and major bleeding events in patients with atrial fibrillation (AF) treated with either vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs) include prior stroke or transient ischemic attack (TIA), concomitant therapy with antiplatelet or non-steroidal anti-inflammatory drugs (NSAIDs), heart failure, abnormal liver function, and older age, according to study results published in BMJ Open.

The PREvention oF thromboembolic events – European Registry in Atrial Fibrillation (PREFER in AF) registry (mean patient age, 72±10 years) was used to obtain data of patients who received a VKA (n=5310). In addition, the researchers included patients from an independent PREFER in AF Prolongation validation cohort who had received a NOAC (n=3156). Participants were from Austria, France, Germany, Italy, Spain, Switzerland, and the United Kingdom.

The investigators identified risk factors for thromboembolic events, including ischemic stroke and systemic embolism. Risk factors for major bleeding (eg, gastrointestinal bleeding, intracerebral hemorrhage, and other life-threatening bleeding) were also identified.

At 1-year follow-up, the incidence rate of thromboembolic events was 2.34% (95% CI, 1.93-2.74), whereas the incidence of major bleeding events was 2.84% (95% CI, 2.41-3.33). In the PREFER in AF cohort, there were independent associations between thromboembolic events and abnormal liver function (odds ratio [OR], 2.86; 95% CI, 1.24-6.63; P =.0141), prior stroke or TIA (OR, 2.79; 95% CI, 1.81-4.28; P <.0001), labile international normalized ratio ([INR]; OR, 2.83; 95% CI, 1.83-4.38; P <.0001), concomitant therapy with antiplatelet or NSAIDs (OR, 2.41; 95% CI, 1.58-3.69; P <.0001), heart failure (OR, 2.20; 95% CI, 1.45-3.33; P =.0002), and age ≥75 years (OR, 1.53; 95% CI, 1.00-2.33; P =.0482).

In the multivariable analysis, independent associations were also found between major bleeding events and bleeding history (OR, 3.87; 95% CI, 2.32-6.47; P <.0001), age ≥75 years (OR, 1.99; 95% CI, 1.36-2.91; P =.0004), presence of vascular disease (OR, 1.65; 95% CI, 1.11-2.43; P =.0125), abnormal renal function (OR, 1.50; 95% CI, 1.01-2.23; P =.0401), and abnormal liver function (OR, 3.24; 95% CI, 1.47-7.15; P =.0035).

The researchers were able to validate these risk factors in the cohort of patients who received NOACs. There was a 30% reduced risk for major bleeding for each single point reduction on a modifiable bleeding risk scale (OR, 0.70; 95% CI, 0.64-0.76; P <.01). For each 1-point decrease on the modifiable scale, there was also a 28% lower rate of thromboembolic events (OR, 0.72; 95% CI, 0.66-0.82; P <.01).

A limitation of the analysis was the inclusion of only patients from 7 European countries, which may reduce the ability to generalize the findings across geographic variations in care and patient demographics.

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“Our findings suggest that normalizing INR, avoiding exposure to antiplatelet agents or NSAIDs and preventing liver disease could reduce both bleeding and residual stroke risk in AF patients receiving anticoagulation,” the researchers concluded.


This study was supported by Daiichi-Sankyo Europe.


Rohla M, Weiss TW, Pecen L, et al. Risk factors for thromboembolic and bleeding events in anticoagulated patients with atrial fibrillation: the prospective, multicentre observational PREvention oF thromboembolic events – European Registry in Atrial Fibrillation (PREFER in AF). BMJ Open. 2019;9(3):e022478.