Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data from VigiBase

Abstract

Purpose The aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs. Methods The WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed. Results By January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one. Conclusions Fatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

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“…Je známo, že kombinace aspirinu s některými dalšími léčivy může vést ke zdravotním potížím ale i k smrti 99 . Předávkování aspirinem je velmi vzácné, i když není vyloučeno; příznakem může být tinnitus (hučení a pískání v uších), hyperventilace, zvracení, dehydratace, horečka, dvojité vidění a pocit na omdlení.…”

Spectrophotometric resolution for quantitative analysis of aspirin and rivaroxaban combination therapy in biological fluids using simple and eco-friendly procedure

“…Furthermore, rivaroxaban is the only anticoagulant approved so far to be taken in combination with aspirin to reduce the risk of major thrombotic vascular events in peripheral artery disease (PAD) patients. It is also worth mentioning that in some cases fatal adverse effects related to rivaroxaban combined with aspirin were reported in some patients which recommends the proper monitoring of coagulation during rivaroxaban treatment along with proper attention to dosage error [ 9 , 10 ].

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