direct oral anticoagulant; novel oral anticoagulant (DOAC, NOAC)
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Introduction
A term applied collectively to newer oral anticoagulants developed to replace warfarin
Indications
- prophylaxis for venous thromboembolism
- more effective for preventing venous thromboembolism in elderly & in patients with cancer than warfarin[1]
- no more or less effective in the prevention of recurrent venous thromboembolism than warfarin[6]
- treatment of venous thromboembolism
- direct oral anticoagulants comparable to warfarin in patients with cancer-related venous thromboembolism[3]
- apixaban more effective with less major bleeding than rivaroxaban[27]
- short-term rates of recurrence of thromboembolism & major bleeding similar with rivaroxaban vs apixaban[30]
- cancer-related VTE recurrence & major bleeding are similar in apixaban, rivaroxaban, & enoxaparin[31]
- rivaroxaban is associated with higher bleeding but lower mortality compared to apixaban & enoxaparin[31]
- atrial fibrillation
- prevention of embolic stroke
- efficacy similar to warfarin[7][10]
- efficacy equal or greater than warfarin[8]
- safe & effective alternatives to warfarin in a routine care setting[1]
- reduced all-cause mortality relative to warfarin[20]
- apixaban appears to be direct oral anticoagulant of choice[20]
- apixaban with 5-fold higher risk of stroke when underdosed[15]
- apixaban 5 mg PO BID may not increase risk of hemorrhagic stroke[24]
- dabigatran & rivaroxaban not associated with higher risk of stroke when underdosed[15]
- reduces all-cause mortality relative to warfarin[2]
- risks of death, any bleeding, or major bleeding lower for apixaban & dabigatran compared with warfarin[10]
- use within 7 days of ischemic stroke appears safe[12]
- prevention of embolic stroke
- better than warfarin for preventing stroke & systemic embolism in patients with atrial fibrillation & early-stage renal failure[29]
- treatment of acute heparin-induced thrombocytopenia[16]
- ST segment elevation myocardial infarction (STEMI)[22] as add-on to antiplatelet therapy
Contraindications
- creatinine clearance < 30 ml/min, ESRD[5]
- of no benefit for NSTEMI[22]
- valvular heart disease, valvular atrial fibrillation due to rheumatic heart disease[5]
- morbid obesity (BMI >40 mg/kg)[42]
- high-risk antiphospholipid antibody syndrome
* questionable
- pregnancy
- osteoporosis (GRS11: due to increased fracture risk relative to warfarin)[42]
- ref[41] concludes decreased fracture risk relative to warfarin
- end-stage renal disease
- left ventricular thrombus, catheter-associated deep venous thrombosis, splanchnic vein thrombosis, cerebral venous thrombosis[45]
Benefit/risk
- STEMI: NNT= 63 to prevent one cardiovascular event; NNH = 96 to cause one major bleeding event[22]
- NSTEMI: NNT= 130 to prevent one cardiovascular event; NNH = 137 to cause one major bleeding event[22]
Dosage
- renal dosing underprescribed 43% of time[15]
- stop 24-36 hours prior to standard-risk surgery* & 2-4 days prior to high-risk surgery in patients with normal renal function[5]
- stop 24 hours prior to GI endoscopy & resume 24 hours after for low risk procedures & 48 hours later for high risk procedures in patients with atrial fibrillation[44]
* includes colonoscopy or other endoscopic procedure during which biopsy may occur[5] (also see perioperative anticoagulation)
Pharmacokinetics
- 1/2 life varies 7-20 hours
- betrixaban with longest 1/2 life of 20 hours
- rivaroxaban with shortest 1/2 life of 7-11 hours
- renal clearance varies from 80% for dabigatran vs 5% for betrixaban (apixaban 25%, edoxaban 35%, rivaroxaban 66%)[5]
Adverse effects
- major bleeding, including intracranial hemorrhage, & fatal hemorrhage ~40% less frequent than with warfarin[1]
- no more or less major bleeding than warfarin[6][19]
- 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][9][21][23]
- 15-20 mg QD of rivaroxaban associated with increased risk of intracranial hemorrhage; smaller daily doses of rivaroxaban or apixaban are not[24]
- risk of bleeding similar to warfarin[6][7][8]
- risk of GI bleeding less than warfarin (RR=0.25)[14]
- apixaban with lowest risk of GI bleed [13,23, 43]
- lowest risk of GI bleed in patients > 75 years
- risk < 1/2 that with rivaroxaban (highest risk)[37]
- rates of ischemic stroke, systemic embolism, intracranial hemorrhage & all-cause mortality similar for apixaban, dabigatran, edoxaban, & rivaroxaban for patients with atrial fibrillationincluding for patients >= 80 years & those with chronic kidney disease[43]
- among Medicare recipients with atrial fibrillation >= 65 years, apixaban is associated with lower risk of major ischemic events & major hemorrhage than rivaroxaban[39]
- coadministration of proton pump inhibitor
- may decrease risk of upper GI bleed[26]
- does not decrease risk of upper GI bleed[32]
- decreases risk of subtherapeutic DOAC levels in frail elderly*
- no bleeding complications with joint aspiration or joint injection[17]
- risk of new-onset osteoporosis less than that of warfarin[40]
- risk of bone fracture less than warfarin[41]
- risk of death in nursing home residents less than warfarin
- increased risk of bleeding with untreated respiratory tract infections[38]
- 55% of frail elderly have either subtherapeutic or supratherapeutic levels*[46]
- 40% with supratherapeutic levels, 14% with subtherapeutic levels
- rivaroxaban associated with higher risk of supratherapeutic levels (RR=1.8)
- chronic renal failure stage 4 associated with higher risk of supratherapeutic levels (RR=2.4)
- proton pump inhibitor use associated with lower risk of subtherapeutic levels (RR=0.09)
* frail elderly admitted with acute illness[46]
Drug interactions
- may interact with amiodarone, fluconazole, rifampin, & phenytoin in Haan Chinese[18]
- concurrent uses of DOAC & aspirin associated with increased bleeding & hospitalizations but similar rate of thrombosis[35]
- concurrent use of macrolides may increase risk of bleeding[38]
- drug interaction(s) of oral anticoagulants with selective serotonin reuptake inhibitor (SSRI)
- drug interaction(s) of aspirin, P2Y12 inhibitors & anticoagulants
Notes
- recommened checklist for patients on direct oral anticoagulants[4]
- idarucizumab for dabigatran reversal[28]
- andexanet alfa for apixaban & rivaroxaban reversal[28]
- non-specific prohemostatic agents such as prothrombin complex concentrate have also been used for DOAC reversal[28]
* DOAC reversal agents associated with an effective hemostasis rate of 78.5%[36]
* failure to achieve hemostasis with reversal agent(s) predicts mortality after severe DOAC-relating bleeds (RR=3.63)[36]
More general terms
More specific terms
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 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 Vedovati MC et al. Direct oral anticoagulants in patients with VTE and cancer: A systematic review and meta-analysis. Chest 2015 Feb; 147:475. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25211264
- ↑ 4.0 4.1 Gladstone DJ, Geerts WH, Douketis J et al How to Monitor Patients Receiving Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Practice Tool Endorsed by Thrombosis Canada, the Canadian Stroke Consortium, the Canadian Cardiovascular Pharmacists Network, and the Canadian Cardiovascular Society. Ann Intern Med. 2015 Jun 30. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26121536 <Internet> http://annals.org/article.aspx?articleid=2362311
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19. American College of Physicians, Philadelphia 2015, 2018, 2021.
- ↑ 6.0 6.1 6.2 6.3 Robertson L, Kesteven P, McCaslin JE. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism. Cochrane Database Syst Rev. 2015 Dec 4;12:CD010957 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26636644
- ↑ 7.0 7.1 7.2 Salazar CA, del Aguila D, Cordova EG. Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non- valvular atrial fibrillation. Cochrane Database Syst Rev. 2014 Mar 27;3:CD009893. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24677203
- ↑ 8.0 8.1 8.2 Sardar P, Chatterjee S, Chaudhari S, Lip GYH. New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc. 2014;62(5):857-864 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24786913
- ↑ 9.0 9.1 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
- ↑ 10.0 10.1 10.2 Larsen TB et al Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 2016;353:i3189 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27312796 Free full text <Internet> http://www.bmj.com/content/353/bmj.i3189
- ↑ Tran H, Joseph J, Young L, McRae S et al New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Australasian Society of Thrombosis and Haemostasis. Intern Med J. 2014 Jun;44(6):525-36. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24946813
- ↑ 12.0 12.1 Seiffge DJ et al. Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events. Neurology 2016 Sep 30 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27694266
- ↑ Noseworthy PA, Yao X, Abraham NS et al. Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in nonvalvular atrial fibrillation. Chest 2016 Dec; 150:1302. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27938741
Abraham NS, Noseworthy PA, Yao X, 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 - ↑ 14.0 14.1 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
- ↑ 15.0 15.1 15.2 15.3 Yao X, Shah ND, Sangaralingham LR et al Non-Vitamin K Antagonist Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Renal Dysfunction. J Am Coll Cardiol. 2017 Jun 13;69(23):2779-2790. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28595692
Pokorney SD, Peterson ED, Piccini JP. When Less Is Not More. J Am Coll Cardiol. 2017 Jun 13;69(23):2791-2793. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28595693 - ↑ 16.0 16.1 Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: Update of Hamilton experience and literature review. Blood 2017 Jun 23; blood-2017-04-778993 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28646118 <Internet> http://www.bloodjournal.org/content/early/2017/06/23/blood-2017-04-778993
- ↑ 17.0 17.1 Yui JC, Preskill C, Greenlund LS. Arthrocentesis and joint injection in patients receiving direct oral anticoagulants. Mayo Clin Proc 2017 Aug; 92:1223 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28778256 <Internet> http://www.mayoclinicproceedings.org/article/S0025-6196(17)30310-5/fulltext
- ↑ 18.0 18.1 Chang SH, Chou IJ, Yeh SH Association Between Use of Non-Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation. JAMA. 2017;318(13):1250-1259 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28973247 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2656168
- ↑ 19.0 19.1 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
- ↑ 20.0 20.1 20.2 Lopez-Lopez JA, Sterne JAC, Thom HHZ et al Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ 2017;359:j5058 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29183961 Free full text <Internet> http://www.bmj.com/content/359/bmj.j5058
Ball J. Which anticoagulant for stroke prevention in atrial fibrillation? BMJ 2017;359:j5399 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29183874 <Internet> http://www.bmj.com/content/359/bmj.j5399 - ↑ 21.0 21.1 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
- ↑ 22.0 22.1 22.2 22.3 22.4 Chiarito M, Cao D, Cannata F et al Direct Oral Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention After Acute Coronary Syndromes. A Systematic Review and Meta-analysis. JAMA Cardiol. Published online February 7, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29417147 https://jamanetwork.com/journals/jamacardiology/article-abstract/2672050
- ↑ 23.0 23.1 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
- ↑ 24.0 24.1 24.2 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
- ↑ Lowenstern A, Al-Khatib SM, Sharan L et al. Interventions for preventing thromboembolic events in patients with atrial fibrillation: A systematic review. Ann Intern Med 2018 Oct 30; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30383133
- ↑ 26.0 26.1 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
- ↑ 27.0 27.1 Dawwas GK, Brown J, Dietrich E, Park H. Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: A retrospective population-based cohort analysis. Lancet Haematol 2019 Jan; 6:e20 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30558988 https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30191-1/fulltext
Dawwas GK, Leonard CE, Lewis JD et al. Risk for recurrent venous thromboembolism and bleeding with apixaban compared with rivaroxaban: An analysis of real-world data. Ann Intern Med 2021 Dec 7; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34871048 https://www.acpjournals.org/doi/10.7326/M21-0717 - ↑ 28.0 28.1 28.2 28.3 Cuker A, Burnett A, Triller D et al. Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum. Am J Hematol 2019 Jun; 94:697. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30916798 https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25475
- ↑ 29.0 29.1 Ha JT, Neuen BL, Cheng LP et al Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med. 2019. July 16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31307056 https://annals.org/aim/article-abstract/2738158/benefits-harms-oral-anticoagulant-therapy-chronic-kidney-disease-systematic-review
Hildebrand A, Ribic C, Zimmerman D. Balancing the Benefits and Harms of Oral Anticoagulation in Chronic Kidney Disease: What Does Available Evidence Tell Us? Ann Intern Med. 2019. July 16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31307054 https://annals.org/aim/article-abstract/2738159/balancing-benefits-harms-oral-anticoagulation-chronic-kidney-disease-what-does - ↑ 30.0 30.1 Bott-Kitslaar DM, Bott-Kitslaar DM et al. Apixaban and rivaroxaban in patients with acute venous thromboembolism. Mayo Clin Proc 2019 Jul; 94:1242 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30737059 https://www.mayoclinicproceedings.org/article/S0025-6196(18)30895-4/fulltext
- ↑ 31.0 31.1 31.2 Wysokinski WE, Houghton DE, Casanegra AI et al Comparison of Apixaban to Rivaroxaban and Enoxaparin in Acute Cancer-Associated Venous Thromboembolism. Am J Hematol. 2019 Aug 4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31378995
- ↑ 32.0 32.1 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
Moayyedi P, Eikelboom JW, Bosch J et al et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019 Sept. 157(3):682-691. epub May 29. https://www.gastrojournal.org/article/S0016-5085(19)40974-8/fulltext - ↑ 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
- ↑ 35.0 35.1 Schaefer JK, Errickson J, Li Y et al Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication. JAMA Intern Med. Published online April 19, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33871544 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2778963
- ↑ 36.0 36.1 36.2 Lou N DOAC Antidotes No Panacea for Fatal Bleeds. Aim for effective hemostasis by any means necessary, meta-analysis suggests, MedPage Today June 14, 2021 https://www.medpagetoday.com/cardiology/prevention/93096
Gomez-Outes A, Alcubilla P, Calvo-Rojas G et al Meta-Analysis of Reversal Agents for Severe Bleeding Associated With Direct Oral Anticoagulants. J Am Coll Cardiol. 2021 Jun, 77 (24) 2987-3001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34140101 https://www.jacc.org/doi/10.1016/j.jacc.2021.04.061 - ↑ 37.0 37.1 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
- ↑ 38.0 38.1 38.2 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
- ↑ 39.0 39.1 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
- ↑ 40.0 40.1 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
- ↑ 41.0 41.1 41.2 Sugiyama T An update on hip fracture risk associated with anticoagulant therapy: warfarin versus direct oral anticoagulants. Expert Opinion on Drug Safety. 2020 19(10):1219-1220 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32795203
- ↑ 42.0 42.1 42.2 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ 43.0 43.1 Lau WCY, Torre CO et al Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation. A Multinational Population-Based Cohort Study. Annals of Internal Medicine. 2022. Nov 1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36315950 https://www.acpjournals.org/doi/10.7326/M22-0511
- ↑ 44.0 44.1 Hansen-Barkun C et al. Periprocedural management of patients with atrial fibrillation receiving a direct oral anticoagulant undergoing a digestive endoscopy. Am J Gastroenterol 2023 May; 118:812. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36434811 https://journals.lww.com/ajg/Abstract/2023/05000/Periprocedural_Management_of_Patients_With_Atrial.17.aspx
- ↑ 45.0 45.1 Bejjani A, Khairani CD, Assi A et al When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review. J Am Coll Cardiol. 2024 Jan 23;83(3):444-465 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38233019 Review. https://www.sciencedirect.com/science/article/abs/pii/S073510972308052X
- ↑ 46.0 46.1 46.2 de Jong MJ, Saadan H, Hellenbrand DLS et al The DOAC-FRAIL study, evaluation of direct oral anticoagulant-levels in acutely admitted frail older patients: An exploratory study. J Am Geriatr Soc. 2024 Mar 29 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38553825 No abstract available. https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.18894