Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin: a sequential cohort study

Abstract

ObjectivesThe aim of this study was to compare effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin in the Australian Veteran population.DesignSequential cohort study using inverse probability of treatment weighting (IPTW) and propensity score matching. Initiators of high-strength (apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg) and low-strength DOACS (apixaban 2.5 mg, dabigatran 110 mg, rivaroxaban 15 mg) were compared with warfarin initiators.SettingAustralian Government Department of Veterans’ Affairs claims database.Participants4836 patients who initiated oral anticoagulants (45.8%, 26.0% and 28.2% on low-strength, high-strength DOACs and warfarin, respectively) between August 2013 and March 2015. Mean age was 85, 75 and 83 years for low-strength, high-strength DOACs and warfarin initiators, respectively.Main outcome measuresOne-year risk of hospitalisation for ischaemic stroke, any bleeding event or haemorrhagic stroke. Secondary outcomes were 1-year risk of hospitalisation for myocardial infarction and death.ResultsUsing the IPTW method, no difference in risk of ischaemic stroke or bleeding was found with low-strength DOACs compared with warfarin. As a class, no increased risk of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban (HR 2.25, 95% CI 1.23 to 4.13). For high-strength DOACs, no difference was found for ischaemic stroke compared with warfarin, however, there was a significant reduction in risk of bleeding events (HR 0.63, 95% CI 0.44 to 0.89) and death (HR 0.40, 95% CI 0.28 to 0.58). Propensity score matching showed no difference in risk of ischaemic stroke or bleeding.ConclusionWe found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

“…Fifteen articles probably extracted from the identical database or the same population were not applied [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Sixteen articles investigating non-Asians or not fully Asians were not enrolled [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”

“…Fifteen articles probably extracted from the identical database or the same population were not applied [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Sixteen articles investigating non-Asians or not fully Asians were not enrolled [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. Finally, six articles were included for meticulous evaluation after eliminating the references violating the inclusion criteria.…”

Generating Real-World Evidence on the Quality Use, Benefits and Safety of Medicines in Australia: History, Challenges and a Roadmap for the Future

“…The ecological studies investigated clinical outcomes, such as mortality, overdose and poisoning, and were most often generated from publicly available data. Second, studies based on person-level and linked data, which addressed medicines safety outcomes such as infections, development of other health conditions, birth defects, hospitalisations (e.g., for myocardial infarction, pneumonia, falls, and fractures, and death) [49][50][51][52][53]. Studies examining effectiveness measured mostly survival or hospitalisations for specific conditions (e.g., heart failure rehospitalisation following post-discharge beta-blocker initiation) [54].…”

Supporting anticoagulant treatment decision making to optimise stroke prevention in complex patients with atrial fibrillation: a cluster randomised trial

“…Moreover, DOACs have been preferentially prescribed to younger patients, those with lower bleeding risks, fewer comorbidities and/or with lower stroke risk [50][51][52][53]. This has also been shown to occur in Australia, where patients with lower comorbidity burden are preferentially prescribed higher dose DOACs [57]. The underuse of anticoagulation in patients over the age of 85 remains significant [43].…”