Incidence Rates of Bleeding and Emergency Surgery Due to Trauma or Fracture Among Japanese Patients with Non-valvular Atrial Fibrillation Receiving Oral Anticoagulation Therapy

Introduction In patients with nonvalvular atrial fibrillation (NVAF) receiving oral anticoagulants (OACs), reversal of coagulopathy can be achieved with specific reversal drugs such as idarucizumab, which is indicated for use in patients treated with dabigatran for cases of life-threatening or uncontrolled bleeding or during emergency procedures that may cause serious bleeding. This study examined the incidence rate (IR) of emergency surgeries and major bleeding episodes associated with fractures and trauma in Japanese patients with NVAF receiving OACs. Methods This retrospective, non-interventional analysis of health insurance claims was conducted using data from 62,888 OAC-naive adult patients with NVAF who initiated dabigatran, warfarin, apixaban, rivaroxaban, or edoxaban between March 2011 and June 2016. The primary endpoint was overall IR of emergency surgery or major bleeding due to fracture or trauma. Results Overall IR of emergency surgery or major bleeding due to fracture or trauma considering outcomes until OAC discontinuation was 0.489 per 100 patient-years (PY) (95% confidence interval [CI] 0.406-0.572). Considering first OAC exposure only, the IR was 0.483 per 100 PY (95% CI 0.394-0.573). Emergency surgery/major bleeding events due to fracture or trauma was highest in those aged >= 75 years (0.611 per 100 PY [95% CI 0.481-0.741]). Conclusions Fewer than one in 200 patients per year with NVAF receiving OACs experience emergency surgeries and major bleeding episodes associated with fractures and trauma; however, the IR of these events is markedly higher in patients of advanced age. Plain Language Summary Patients with an abnormal heart rhythm (nonvalvular atrial fibrillation [NVAF]) have a higher risk of blood clots and stroke (which is when the blood supply to part of the brain is blocked). To reduce these risks, patients can take anticoagulants that slow or prevent the formation of blood clots. However, if the patient needs major emergency surgery or has a severe injury, the anticoagulants can increase their risk of bleeding, which can sometimes be life-threatening. There are drugs (e.g., idarucizumab) that can be used to reverse the effects of anticoagulants in this type of emergency. What we don't know is how many NVAF patients in Japan who are on anticoagulants have emergency surgeries or major bleeding after an injury, and therefore may require a reversal drug. The authors looked at Japanese health insurance claim data from 62,888 adult patients with NVAF who started taking an anticoagulant. They found that, annually, approximately 0.5% of the patients had emergency surgery or a major bleed associated with a fracture or injury. In very elderly patients (aged at least 75 years), the annual percentage was approximately 0.6%, which was almost double the annual percentage in patients aged less than 65 years. The authors concluded that, even though the number of people requiring a reversal agent are quite small, it is important to have an effective reversal agent for patients on anticoagulants, particularly older patients.