Vergleich der Wirksamkeit und Sicherheit nicht-Vitamin-K-abhängiger oraler Antikoagulanzien in der primären Schlaganfallprävention bei Vorhofflimmern
Zusammenfassung der Projektergebnisse
The initial research objective of this project was to assess the comparative effectiveness (i.e., risk of stroke) and safety (i.e., risk of major bleeding) of the blood thinners non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (NVAF) in the setting of realworld clinical practice. However, given the large numbers of studies that were published in this area during the first months of this project, I decided to deviate from the initial research objective and focus instead on other, less studied aspects of NOACs such as non-bleeding safety outcomes and drug-drug interactions. The first study of this project aimed to assess the utilization of NOACs in the Canadian Province of Québec. Using the linked computerized healthcare databases from Québec, we identified predictors of initiation of oral anticoagulation with NOACs versus the older blood thinners vitamin K antagonists (VKAs). Moreover, we assessed the longer-term treatment persistence of NOACs and VKAs. The study included 62,867 patients diagnosed with NVAF in or after January 2011, when NOACs became available in Québec. It showed that an increasing number of patients newly diagnosed with NVAF in Québec receives NOACs as the initial oral anticoagulation, but advanced age and high thromboembolic risk are associated with a lower probability of initiating NOACs compared with VKAs. Finally, NVAF patients receiving NOACs show a higher long‐term treatment persistence than NVAF patients receiving VKAs, and the introduction of NOACs has doubled treatment persistence. The second study of this project aimed to assess the liver safety of NOACs. Using the linked computerized healthcare databases from Québec, we determined whether the use of NOACs was associated with an increased risk of serious liver injury compared with the use of VKAs in NVAF patients with and without prior liver disease. The study included 48,109 NVAF patients without prior liver disease and 3,778 NVAF patients with prior liver disease. It showed that compared with VKAs, NOACs are not associated with an increased risk of serious liver injury in NVAF patients with or without prior liver disease. Thus, liver status should not be a central part of physician decision making regarding the appropriate oral anticoagulation for stroke prevention in the setting of NVAF. The third study of this project aimed to assess the risk of major bleeding with the concomitant use of NOACs with antiplatelet agents, which are less potent blood thinners. Using the linked computerized healthcare databases from Québec, we compared the risk of intracranial hemorrhage, gastrointestinal bleeding, and other major bleeding between the concomitant use of NOACs with antiplatelet agents and the concomitant use of VKAs with antiplatelet agents in NVAF patients. The study included 5,301 NVAF patients initiating concomitant NOAC-antiplatelet use and 9,106 NVAF patients initiating concomitant VKA-antiplatelet use. It showed that compared with concomitant VKA-antiplatelet use, concomitant NOAC-antiplatelet use is associated with a similar risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage and other major bleeding. These findings could help physician decision-making in patients requiring concomitant treatment with oral anticoagulants and antiplatelets.
Projektbezogene Publikationen (Auswahl)
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“Patterns of long-term use of new anticoagulants for non-valvular atrial fibrillation: Quebec observational study” Pharmacoepidemiol Drug Saf. 2017 Dec;26(12):1546-1554
Douros A, Renoux C, Coulombe J, Suissa S
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“Non-vitamin K antagonist oral anticoagulants and risk of serious liver injury” J Am Coll Cardiol. 2018 Mar;71(10):1105-1113
Douros A, Azoulay L, Yin H, Suissa S, Renoux C
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“Concomitant use of direct oral anticoagulants with antiplatelet agents and the risk of major bleeding in patients with non-valvular atrial fibrillation” Am J Med. 2019 Feb;132(2);191-199.e12
Douros A, Renoux C, Yin H, Filion KB, Suissa S, Azoulay L
