Reduced Dose Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation
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Purpose of Review
Doses of direct oral anticoagulants (DOACs) are often reduced in older adults based on age, renal function, and bleeding risk. This review assesses recent evidence for safety and efficacy of reduced dose DOAC regimens in older adults.
Dabigatran 110 mg twice daily shows similar efficacy and similar or lower bleeding risk compared to 150 mg twice daily in several studies. Dabigatran 110 mg is approved outside the USA and can be considered in ages > 75–80, or in patients with a propensity for higher dabigatran blood levels. Rivaroxaban 15 mg, apixaban 2.5 mg, and edoxaban 30 mg are safe and effective when used appropriately in patients who qualify based on labeled dosing. Limited evidence suggests inappropriately dose-reduced DOACs may increase risk for thromboembolic events.
Besides dabigatran, dose reduction of apixaban, rivaroxaban, and edoxaban should be limited to patients who qualify based on FDA-approved parameters. The risk of stroke and bleeding should be carefully considered and discussed with each patient when deciding whether to reduce a DOAC dose off-label.
KeywordsDirect oral anticoagulant Elderly Low dose Reduced dose
Compliance with Ethical Standards
Conflict of Interest
Silu Zuo, Billy Chen, Akash Kataruka, and Sean Bell declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370–5.CrossRefGoogle Scholar
- 7.• Steinberg BA, Shrader P, Pieper K, et al (2018) Frequency and outcomes of reduced dose non-vitamin K antagonist anticoagulants: results from ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II). J Am Heart Assoc. doi: https://doi.org/10.1161/JAHA.117.007633. This study assesses the factors leading why DOACs are dose-reduced, and suggests reasons for dose reduction are not always expected (lower doses seen more in younger patients with lower bleed risk).
- 8.• Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GYH, Larsen TB (2017) Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 356:j510. This is the only study to date to assess the effectiveness and safety of common reduced-dose regimens of DOACs.Google Scholar
- 10.Pradaxa® package insert. Accessed Oct 13 2018. https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf.
- 11.Pradaxa Canada Monograph. Accessed 13 Oct 2018. https://www.boehringer-ingelheim.ca/sites/ca/files/documents/pradaxapmen.pdf.
- 18.Šinigoj P, Malmström RE, Vene N, Rönquist-Nii Y, Božič-Mijovski M, Pohanka A, et al. Dabigatran concentration: variability and potential bleeding prediction in “real-life” patients with atrial fibrillation. Basic Clin Pharmacol Toxicol. 2015;117:323–9.Google Scholar
- 20.Halperin JL, Hankey GJ, Wojdyla DM, Piccini JP, Lokhnygina Y, Patel MR, et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation. 2014;130(2):138–46.CrossRefGoogle Scholar
- 25.Alexander JH, Andersson U, Lopes RD, Hijazi Z, Hohnloser SH, Ezekowitz JA, et al. Apixaban 5 mg twice daily and clinical outcomes in patients with atrial fibrillation and advanced age, low body weight, or high creatinine: a secondary analysis of a randomized clinical trial. JAMA Cardiol. 2016;1:673–81.CrossRefGoogle Scholar
- 27.Kato ET, Giugliano RP, Ruff CT, et al (2016) Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 20;5(5)Google Scholar
- 35.Sharma M, Cornelius VR, Patel JP, Davies JG, Molokhia M. Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: systematic review and meta-analysis. Circulation. 2015;132:194–204.CrossRefGoogle Scholar