Evolución del consumo y análisis de la eficacia y seguridad de la anticoagulación oral en un área de salud desde la comercialización de los anticoagulantes orales de acción directa

Resumo

Oral anticoagulant (OAC)therapy, as prophylaxis of thromboembolic disease, is a frequent indication in clinical practice. Until a few years ago, only vitamin K antagonists (VKAs) were available. With the commercialization of direct-acting oral anticoagulants (DOACs), which have been shown to be at least as effective and safe as VKA in the prevention of stroke associated with non-valvular atrial fibrillation, the therapeutic arsenal has been expanded. Objective To evaluate the consumption of the OACs from 2011 to 2017 and the impact on pharmaceutical spending that has involved the incorporation of DOACs in a health area. To know the prevalence of potential drug-drug interactions (DDIs) described in the bibliography for OACs and to perform a descriptive and inferential analysis. To determine the efficacy and safety of DOACs compared to VKAs in clinical practice. Material and methods Retrospective descriptive observational study, developed in two phases. In the first phase, a study on the evolution of oral anticoagulation consumption was carried out since the authorization of the first DOAC in 2011 until the year 2017. The information was obtained through the database that manages the prescriptions dispensed in the community pharmacies, performing a calculation of the number of defined daily dose (DDD) per 1,000 inhabitants-day consumed annually. The economic impact of the incorporation of DOACs was also calculated. The second phase of the study consisted of an analysis of the efficacy and safety of the DOACs compared with the VKAs. For this, of patients on anticoagulant treatment during the year 2017, the information of both ischemic and hemorrhagic events was collected through the Minimum Basic Data Set (MBDS) of the Emergency Department and the Neurology Section.Data on concomitant drugswith potential DDIs was also collected to analyze its prevalence and evaluate its associationwith the efficacy and safety of OACs. To identify the factors associated to the presence of potential DDIs, multivariatelogistic regression was used by calculating the adjusted Odds Ratio (OR); and to identify the factors associated with the appearance of ischemicor hemorrhagic events, univariate logistic regression was used by calculating the unadjusted OR. Results In the first phase of the study, the consumption of the DOACs increased from 0.04 in 2011 to 3.35 DDD per 1000 inhabitant-days in 2017, mainly due to the consumption of rivaroxaban. VKAs increased discretely from 5.29 to 5.76 DDD per 1000 inhabitant-days, due to the increase in warfarin consumption, with acenocoumarol being the only anticoagulant that decreased its use. At the end of the study period, the DOACs accounted for 36.7% of the total anticoagulant consumption. Pharmaceutical spending experienced a marked increase, rising the cost per patient by 800%. In the second phase of the study, 4,146 patients were anticoagulated in the health area. Forty percent of them were over 80 years old and 76.3% presented at least one potential DDIs that enhances the anticoagulant effect. Patients treated with VKA had a higher risk of presenting interactions (OR= 2.16, 95% CI: 1.85-2.53). No significantdifferences were found between both groups of anticoagulants and the appearance of stroke/systemic embolism. Patients treated with DOACs had a higher risk of major bleeding (OR= 1.78, 95% CI: 1.07-2.95), finding a higher incidence in patients over 80 years of age and those with potential DDIs that enhance the anticoagulant effect.Among patients with hemorrhagic event, those who were anticoagulated with DOACs had a higher risk of hospital admission compared to those treated with VKAs. Conclusions The commercialization of DOACs has led to a change in the prescription profile of oral anticoagulants in the area studied, with a shift towards them, what has meant an abrupt increase in pharmaceutical spending. Rivaroxaban has been the most consumed DOAC. The potential DDIs that enhance the anticoagulant effect were frequent, and higher in the VKA group. Although there were no significant differences in the incidence of stroke/systemic embolism between the two groups, patients treated with DOACs had a higher risk of major bleeding, with a higher incidence in patients older than 80 years and with DDIs that potentiate the anticoagulant effect.