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

Nicole L. Pratt, Emmae Ramsay, Lisa M. Kalisch Ellett, Katherine Duszynski, Sepehr Shakib, Mhairi Kerr, Gillian Caughey, Elizabeth Ellen Roughead

Research output: Contribution to journalArticle

Abstract

Objectives The 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. Design Sequential 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. Setting Australian Government Department of Veterans' Affairs claims database. Participants 4836 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 measures One-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. Results Using 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. Conclusion We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

LanguageEnglish
Article numbere026486
JournalBMJ open
Volume9
Issue number5
DOIs
Publication statusPublished - 1 May 2019
Externally publishedYes

Keywords

  • atrial fibrillation
  • bleeding
  • medication safety
  • oral anticoagulants
  • warfarin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pratt, N. L., Ramsay, E., Kalisch Ellett, L. M., Duszynski, K., Shakib, S., Kerr, M., ... Roughead, E. E. (2019). Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin: A sequential cohort study. BMJ open, 9(5), [e026486]. https://doi.org/10.1136/bmjopen-2018-026486
Pratt, Nicole L. ; Ramsay, Emmae ; Kalisch Ellett, Lisa M. ; Duszynski, Katherine ; Shakib, Sepehr ; Kerr, Mhairi ; Caughey, Gillian ; Roughead, Elizabeth Ellen. / Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin : A sequential cohort study. In: BMJ open. 2019 ; Vol. 9, No. 5.
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Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin : A sequential cohort study. / Pratt, Nicole L.; Ramsay, Emmae; Kalisch Ellett, Lisa M.; Duszynski, Katherine; Shakib, Sepehr; Kerr, Mhairi; Caughey, Gillian; Roughead, Elizabeth Ellen.

In: BMJ open, Vol. 9, No. 5, e026486, 01.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin

T2 - BMJ Open

AU - Pratt, Nicole L.

AU - Ramsay, Emmae

AU - Kalisch Ellett, Lisa M.

AU - Duszynski, Katherine

AU - Shakib, Sepehr

AU - Kerr, Mhairi

AU - Caughey, Gillian

AU - Roughead, Elizabeth Ellen

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Objectives The 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. Design Sequential 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. Setting Australian Government Department of Veterans' Affairs claims database. Participants 4836 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 measures One-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. Results Using 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. Conclusion We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

AB - Objectives The 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. Design Sequential 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. Setting Australian Government Department of Veterans' Affairs claims database. Participants 4836 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 measures One-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. Results Using 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. Conclusion We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

KW - atrial fibrillation

KW - bleeding

KW - medication safety

KW - oral anticoagulants

KW - warfarin

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