Many anticoagulants are indicated as prophylaxis and treatment for conditions that may lead to thromboembolisms or atrial fibrillation. Among those, apixaban, a reversible direct inhibitor of factor Xa, is one of the most popular. Apixaban is known to cause a variety of side effects; however, for this paper, the focus is on hypersensitivity reactions. Although several cases will be referenced from the literature, we present a case with a history of a dermatological disease before the use of a direct oral anticoagulant. A 74-year-old female patient with a history of pemphigus vulgaris and a diagnosis of pulmonary embolism and right distal vein thrombosis managed with apixaban presented with a pruritic coalescent erythematous dermatitis throughout her torso, back, and lower extremities three days post-apixaban treatment. In accordance with her physical examination, the apixaban regimen was withdrawn, and oral dabigatran, a direct thrombin inhibitor, was initiated. At the patient's five-day follow-up, clinical improvement was noted.

The following day, apixaban was replaced with rivaroxaban, while the rash continued to worsen and spread further around his back. After 3 days of DOAC therapy, the patient was reverted back to warfarin and within 24 hours the rash subsided. This case report indicates a potential rare adverse drug reaction that may become more prominent given the increasing utilization of DOACs in clinical practice. Future research is needed to further investigate this adverse event and ensure that providers and patients are aware of it. Additionally, this report documents to our knowledge, the first report of an immediate hypersensitivity reaction to DOACs. There is limited clinical data evaluating anticoagulation with the direct oral anticoagulants (DOACs) in morbidly obese patients. We sought to examine the efficacy in preventing stroke or other systemic embolic events and safety of apixaban, dabigatran, and rivaroxaban, in comparison to warfarin in patients with either a body-mass index (BMI) over 40 kg/m2 and/or a weight over 120 kg.

The final analysis included 90 patients in both arms. Fifty-two percent (n = 41) of patients in the DOAC group were on apixaban therapy, 12% (n = 11) on dabigatran, and 37% (n = 33) on rivaroxaban. The average BMI and weight in the DOAC group were 46.7 kg/m2 and 139.3 kg, respectively. In the warfarin group, average BMI and weight were 45.8 kg/m2 and 135.9 kg, respectively. There were 11 patients who developed a stroke or thromboembolic event in the DOAC group and 10 in the warfarin group (OR 1.11, 95% confidence interval [CI] 0.45-2.78; p = 0.82). The events in the DOAC group consisted of three patients who developed ischemic stroke, three patients who developed DVTs, one who developed a PE, and four patients who developed MIs. There were two major bleeding events in the DOAC group and three events in the warfarin group (p = 0.65).

Frailty status was determined using the Johns Hopkins Claims-based Frailty Indicator score (≥0.20 indicating frailty). Users of apixaban, dabigatran, or rivaroxaban were separately 1:1 matched to warfarin users via propensity-scores, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed for up to 2 years or until an event, insurance disenrollment or end of follow-up. Rates of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In total, 2700, 2784, and 5270 patients were included in the apixaban, dabigatran, and rivaroxaban 1:1 matched analyses to warfarin. At 2 years, neither apixaban nor dabigatran were associated with differences in the hazard of stroke or systemic embolism (HR=0.78; 95% CI=0.46-1.35 and HR=0.94; 0.60-1.45) or major bleeding (HR=0.72; 95% CI=0.49-1.06 and HR=0.87; 95% CI=0.63-1.19) versus warfarin.

In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, there were 5843, 20 079, 27 777, and 19 375 nonvalvular atrial fibrillation patients taking apixaban, dabigatran, rivaroxaban and warfarin, respectively, from June 1, 2012 to December 31, 2016. Propensity-score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any efficacy or safety outcome or the end date of study. Hazard ratios (95% confidence intervals) comparing apixaban, dabigatran, and rivaroxaban with warfarin were: ischemic stroke/systemic embolism (IS/SE), 0.55 (0.43-0.69), 0.82 (0.68-0.98), and 0.81 (0.67-0.97); major bleeding, 0.41 (0.31-0.53), 0.65 (0.53-0.80), and 0.58 (0.46-0.72); and all-cause mortality, 0.58 (0.51-0.66), 0.61 (0.54-0.68), and 0.57 (0.51-0.65). A total of 3623 (62%), 17 760 (88%), and 26 000 (94%) patients were taking low-dose apixaban (2.5 mg twice daily), dabigatran (110 mg twice daily), and rivaroxaban (10-15 mg once daily), respectively. Similar to all-dose NOACs, all low-dose NOACs had lower risk of IS/SE, major bleeding, and mortality when compared with warfarin. In contrast to other standard-dose NOACs, apixaban was associated with lower risks of IS/SE (0.45 [0.31-0.65]), major bleeding (0.29 [0.18-0.46]), and mortality (0.23 [0.17-0.31]) than warfarin.

Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46-0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76-1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72-1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34-0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67-0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90-1.20], P=0.60). All non-vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding.

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What are therapeutic alternatives for Eliquis?

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