Aspirin and novel oral anticoagulants : reporting of adverse drug reactions

Abstract

The introduction of the novel oral anticoagulants (NOACs) into clinical practice provided alternative options for thromboprophylaxis. The aims of the study were to carry out a comparative analysis of adverse drug reactions (ADRs) reported for aspirin and for NOACs, to identify studies on the use of NOACs in peripheral artery disease (PAD) and to analyse patient accessibility to NOACs. The methodology was divided into five phases. (1) Pharmacovigilance (PV) reports from Eudravigilance were used to analyse ADRs for aspirin and for thee NOACs (apixaban, dabigatran and rivaroxaban). Fifteen ADRs were chosen to be analysed for the four medications. Reported ADRs between the years 2013 and 2017 for the four drugs investigated were compared. (2) A questionnaire was developed and validated to collect information from the Maltese population on ADRs encountered while patients were taking aspirin or NOACs. Fifty patients were recruited for the study (25 patients on aspirin, 25 on rivaroxaban). (3) Documented ADRs from PV reports were compared to reported ADRs from patients. (4) A literature search was carried out to identify studies on the use of NOACs in off-label use for PAD. (5) Accessibility of NOACs was evaluated by using the local hospital formulary to identify which NOACs are procured through the National Health Service. Bleeding-related ADRs (38,826/51,391 or 75.6%) were the most frequently reported ADRs in PV reports, with gastrointestinal bleeding (N=25,892) being the most commonly frequently ADR for rivaroxaban (n=12,974), aspirin (n=5,855), dabigatran (n=5,321) and apixaban (n=1,742). Rivaroxaban had the largest number of reported cases of ADRs (n=24,832). For all fifteen ADRs investigated, statistically significant differences were observed between the four medications when comparing reported cases of ADRs. Thirty-six patients recruited for the questionnaire suffered at least one ADR following administration of either aspirin (18 patients) or rivaroxaban (18 patients). Bleeding-related ADRs, were the least reported ADRs by the questionnaire respondents (11 for aspirin and 4 for rivaroxaban). Eight studies analysing the use of NOACs in PAD patients were identified. Rivaroxaban is the only NOAC which is procured through the Maltese National Health Service. Reflections on the findings of the study indicate that: (1) results from the questionnaire differ from results obtained from PV reports. Bleeding-related ADRs were highest in PV reports and were the lowest reported ADRs in patient questionnaires. The result may suggest an under-reporting of ADRs to PV databases which may be considered as minor or less serious when compared to bleeding-related ADRs. Result reflects a bias on the reporting of ADRs to PV databases. (2) The high number of reported ADRs for rivaroxaban compared to dabigatran and apixaban possibly reflect the consumption trends for rivaroxaban. From the three NOACs studied, dabigatran was the first NOAC which was approved for use. Consumption trends show that rivaroxaban is the most used NOAC. (3) Significant differences in ADRs reported for NOACs and aspirin could be due to consumption differences between medications, differences in safety profile or reporting bias. ADRs are more likely to be reported for novel medications such as NOACs which lack safety information as compared to the more conventional drugs such as aspirin. (4) Two identified studies show that when added to aspirin, NOACs have favourable efficacy outcomes compared to aspirin alone when used in PAD patients. (5) More data on the safety and efficacy of NOACs is necessary to help in determining the risk-benefit ratio of therapy.