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drug adverse effects of direct oral anticoagulants

Adverse effects: - major bleeding, including intracranial hemoorhage, & fatal hemorrhage ~40% less frequent than with warfarin [1,2,3] - major bleeding less frequent in elderly & in patients with renal insufficiency than with warfarin [1] - risk of intracranial hemorrhage less than warfarin (RR=0.42) [1,2,3,8,9] - 15-20 mg QD of rivaroxaban associated with increased risk of intracranial hemorrhage; smaller daily doses of rivaroxaban or apixaban are not [10] - risk of GI bleeding less than warfarin (RR=0.25) [6] - apixaban with lowest risk of GI bleed [5,9] - lowest risk of GI bleed in patients > 75 years - risk < 1/2 that with rivaroxaban (highest risk) [15] - among Medicare recipients with atrial fibrillation >= 65 years, apixaban is associated with lower risk of major ischemic events & major hemorrhage than rivaroxaban [17] - coadministration of proton pump inhibitor - may decrease risk of upper GI bleed [11] - does not decrease risk of upper GI bleed [12] - stop 24-36 hours prior to standard-risk surgery* & 2-4 days prior to high-risk surgery in patients with normal renal function [4] - risk of bleeding similar to warfarin [7] - risk of new-onset osteoporosis less than that of warfarin [18] - risk of bone factures less than warfarin [13,19] - risk of death in nursing home residents less than warfarin - increased risk of bleeding with untreated respiratory tract infections [16] * includes colonoscopy or other endoscopic procedure during which biopsy may occur [4] (also see perioperative anticoagulation)

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DRUGS: direct oral anticoagulant FORM: drug adverse effects direct oral anticoagulant

References

  1. Van Es N et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: Evidence from phase 3 trials. Blood 2014 Sep 18; 124:1968 PMID: 24963045 http://www.bloodjournal.org/content/124/12/1968?sso-checked=true
  2. Liew A et al. Comparing mortality in patients with atrial fibrillation who are receiving a direct-acting oral anticoagulant or warfarin: A meta-analysis of randomized trials. J Thromb Haemost 2014 Sep; 12:1419 PMID: 24986568 http://onlinelibrary.wiley.com/doi/10.1111/jth.12651/abstract
  3. Wilson D, Charidimou A, Shakeshaft C et al. Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type. Neurology 2016 Jan 26; 86:360 PMID: 26718576 http://www.neurology.org/content/86/4/360
  4. Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19. American College of Physicians, Philadelphia 2015, 2018, 2021.
  5. Abraham NS et al. Gastrointestinal safety of direct oral anticoagulants: A large population-based study. Gastroenterology 2016 Dec 31 PMID: 28043907
  6. Cangemi DJ, Krill T, Weideman R et al. A comparison of the rate of gastrointestinal bleeding in patients taking non-vitamin K antagonist oral anticoagulants or warfarin. Am J Gastroenterol 2017 Feb 28 PMID: 28244496 http://www.nature.com/ajg/journal/vaop/ncurrent/full/ajg201739a.html
  7. Jun M, Lix LM, Durand M et al Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study. BMJ. 2017 Oct 17;359:j4323 PMID: 29042362, Free full text http://www.bmj.com/content/359/bmj.j4323
  8. Inohara T, Xian Y, Liang L et al Association of Intracerebral Hemorrhage Among Patients Taking Non-Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality. JAMA. Published online January 25, 2018 PMID: 29372247 https://jamanetwork.com/journals/jama/fullarticle/2670103
  9. Vinogradova Y, Coupland C, Hill T, Hippisley-Cox J Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ 2018;362:k2505 PMID: 29973392 https://www.bmj.com/content/362/bmj.k2505
  10. Huang WY, Singer DE, Wu YL et al Association of Intracranial Hemorrhage Risk With Non-Vitamin K Antagonist Oral Anticoagulant Use vs Aspirin Use. A Systematic Review and Meta-Analysis. JAMA Neurol. Published online August 13, 2018 PMID: 30105396 https://jamanetwork.com/journals/jamaneurology/fullarticle/2696416
  11. Ray WA, Chung CP, Murray KT et al Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA. 2018;320(21):2221-2230 PMID: 30512099 https://jamanetwork.com/journals/jama/fullarticle/2717474
  12. Moayyedi P, Eikelboom JW, Bosch J et al. Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, double-blind, placebo-controlled trial. Gastroenterology 2019 Aug; 157:403 PMID: 31054846 https://www.gastrojournal.org/article/S0016-5085(19)36764-2/fulltext
  13. Binding C, Bjerring Olesen J et al. Osteoporotic fractures in patients with atrial fibrillation treated with conventional versus direct anticoagulants. J Am Coll Cardiol 2019 Oct 29; 74:2150. PMID: 31648707 https://www.sciencedirect.com/science/article/pii/S0735109719374613 - Gage BF. Warfarin-induced fractures in atrial fibrillation? J Am Coll Cardiol 2019 Oct 29; 74:2159. PMID: 31648708 https://www.sciencedirect.com/science/article/pii/S0735109719374625
  14. Alcusky M et al. Comparative safety and effectiveness of direct-acting oral anticoagulants versus warfarin: A national cohort study of nursing home residents. J Gen Intern Med 2020 Aug; 35:2329. PMID: 32291717 PMCID: PMC7403286 https://link.springer.com/article/10.1007/s11606-020-05777-3
  15. Ingason AB, Hreinsson JP, Agustsson AS et al. Rivaroxaban is associated with higher rates of gastrointestinal bleeding than other direct oral anticoagulants: A nationwide propensity score-weighted study. Ann Intern Med 2021 Oct 12; [e-pub]. PMID: 34633836 https://www.acpjournals.org/doi/10.7326/M21-1474
  16. Ahmed H, Whitaker H, Farewell D et al. Respiratory tract infection and risk of bleeding in oral anticoagulant users: Self-controlled case series. BMJ 2021 Dec 21; 375:e068037 PMID: 34933893 PMCID: PMC8689396 Free PMC article
  17. Ray WA, Chung CP, Stein CM et al. Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation. JAMA 2021 Dec 21; 326:2395-2404. PMID: 34932078 PMCID: PMC8693217 (available on 2022-06-21) https://jamanetwork.com/journals/jama/fullarticle/2787319
  18. Patil T, Hobson T. Risk of new-onset osteoporosis in single-center veteran population receiving direct oral anticoagulants versus warfarin Thromb Res. 2021 Apr;200:56-63 PMID: 33540293
  19. Sugiyama T An update on hip fracture risk associated with anticoagulant therapy: warfarin versus direct oral anticoagulants. Expert Opinion on Durg Safety. 2020 19(10):1219-1220 PMID: 32795203