drug adverse effects of direct oral anticoagulants
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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 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)
More general terms
References
- ↑ 1.0 1.1 1.2 1.3 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24963045 <Internet> http://www.bloodjournal.org/content/124/12/1968?sso-checked=true
- ↑ 2.0 2.1 2.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24986568 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/jth.12651/abstract
- ↑ 3.0 3.1 3.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26718576 <Internet> http://www.neurology.org/content/86/4/360
- ↑ 4.0 4.1 4.2 Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19. American College of Physicians, Philadelphia 2015, 2018, 2021.
- ↑ 5.0 5.1 Abraham NS et al. Gastrointestinal safety of direct oral anticoagulants: A large population-based study. Gastroenterology 2016 Dec 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28043907
- ↑ 6.0 6.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28244496 <Internet> http://www.nature.com/ajg/journal/vaop/ncurrent/full/ajg201739a.html
- ↑ 7.0 7.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29042362, Free full text <Internet> http://www.bmj.com/content/359/bmj.j4323
- ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/29372247 https://jamanetwork.com/journals/jama/fullarticle/2670103
- ↑ 9.0 9.1 9.2 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: https://www.ncbi.nlm.nih.gov/pubmed/29973392 https://www.bmj.com/content/362/bmj.k2505
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/30105396 https://jamanetwork.com/journals/jamaneurology/fullarticle/2696416
- ↑ 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/30512099 https://jamanetwork.com/journals/jama/fullarticle/2717474
- ↑ 12.0 12.1 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: https://www.ncbi.nlm.nih.gov/pubmed/31054846 https://www.gastrojournal.org/article/S0016-5085(19)36764-2/fulltext
- ↑ 13.0 13.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/31648708 https://www.sciencedirect.com/science/article/pii/S0735109719374625 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/32291717 PMCID: PMC7403286 https://link.springer.com/article/10.1007/s11606-020-05777-3
- ↑ 15.0 15.1 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: https://www.ncbi.nlm.nih.gov/pubmed/34633836 https://www.acpjournals.org/doi/10.7326/M21-1474
- ↑ 16.0 16.1 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: https://www.ncbi.nlm.nih.gov/pubmed/34933893 PMCID: PMC8689396 Free PMC article
- ↑ 17.0 17.1 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: https://www.ncbi.nlm.nih.gov/pubmed/34932078 PMCID: PMC8693217 (available on 2022-06-21) https://jamanetwork.com/journals/jama/fullarticle/2787319
- ↑ 18.0 18.1 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: https://www.ncbi.nlm.nih.gov/pubmed/33540293
- ↑ 19.0 19.1 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: https://www.ncbi.nlm.nih.gov/pubmed/32795203