Back To Search Results

Apixaban

Editor: Biagio Manna Updated: 2/22/2024 5:20:35 PM

Indications

Apixaban is a novel oral anticoagulant (NOAC) approved by the US Food and Drug Administration (FDA) in 2012 for use in patients with nonvalvular atrial fibrillation to reduce the risk of stroke and blood clots, as mentioned below.[1][2] This medication is approved for various other indications, as described below.

FDA-Approved Indications

Apixaban is indicated for use in patients with nonvalvular atrial fibrillation to reduce the risk of stroke and systemic embolism.[3] According to the guidelines of the American Heart Association (AHA)/American College of Cardiology (ACC)/European Respiratory Society (ERS), apixaban is endorsed for use in nonvalvular atrial fibrillation (AF).[4] 

Later, in 2014, apixaban gained approval for the treatment of deep vein thrombosis (DVT),[5] pulmonary embolism (PE),[6] and prophylaxis in DVT, which may lead to PE, in patients who may have undergone knee or hip replacement surgery.[7][8] The drug is also approved for reducing the risk of recurrent DVT and PE after initial therapy.[9]

Off-Label Uses

  • Apixaban has been investigated in the context of COVID-19. Based on a thorough literature review, the current guidelines from the National Institutes of Health (NIH) state that there is insufficient evidence to recommend the use of a therapeutic dose of apixaban for prophylaxis against venous thromboembolism (VTE).
  • The American Society of Hematology (ASH) recommends selecting a direct oral anticoagulant (DOAC) such as dabigatran, rivaroxaban, or apixaban for subacute heparin-induced thrombocytopenia type A (HIT A). This recommendation is supported by a moderate level of certainty in the evidence. ASH suggests DOACs as the preferred anticoagulant for clinically stable patients. However, in emergency settings, parenteral direct thrombin inhibitors are preferred.[10]

Mechanism of Action

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Mechanism of Action

The clotting cascade of apixaban encompasses a complex process comprising multiple factors operating in 3 distinct phases—initiation, propagation, and fibrin formation.

  • Initiation: This step is initiated when the vascular endothelium and the clotting factors are disturbed.
  • Propagation: This step involves the production of large amounts of thrombin at the injury site.
  • Fibrin formation: In this step, thrombin facilitates the conversion of fibrinogen into fibrin. 

The coagulation proteins form the basic components of the coagulation system. They lead to complex reactions, converting plasma-soluble fibrinogen to insoluble fibrin strands. The clotting cascade has 2 main pathways—the intrinsic and extrinsic. External trauma activates the extrinsic pathway and causes blood loss from the vascular system, and it is faster than the intrinsic pathway and involves factor VII. Trauma within the vascular system triggers platelet activation through exposure to endothelium, chemicals, or collagen, thereby potentially initiating the intrinsic pathway, which comprises factors XII, XI, IX, and VIII. Both pathways share a common ending where they activate factor X to Xa, which activates prothrombin (II) to thrombin (IIa), forming a stable clot.

Apixaban is a highly selective direct factor Xa inhibitor that blocks the propagation phase of the coagulation cascade. This affects both free and clot-bound factor Xa. Antithrombotic activity does not need antithrombin III. Factor Xa is a catalyst for converting prothrombin to thrombin, the final step in the coagulation cascade, leading to fibrin and clot formation.[11] Other direct factor Xa inhibitors include rivaroxaban and edoxaban. Apixaban exerts no effect on platelet aggregation.

Pharmacokinetics

Apixaban exhibits dose-linear pharmacokinetics up to a dose of 10 mg.[12]

Absorption: The absolute bioavailability of apixaban is approximately 50% for doses up to 10 mg. Consumption of the drug with food does not alter its bioavailability. The peak plasma concentration of apixaban is typically achieved within 3 to 4 hours post-administration.

Distribution: Apixaban exhibits a plasma protein binding of approximately 87%, indicating high protein binding. In addition, the drug has a volume of distribution of approximately 21 L, suggesting moderate distribution into tissues.

Metabolism: Apixaban is primarily metabolized via the enzyme CYP3A4. Approximately 25% of the orally administered dose of apixaban is eliminated in urine and feces as metabolites.

Elimination: Apixaban undergoes elimination via both urine and feces and has an apparent half-life of 12 hours following oral administration. Among the DOACs, apixaban exhibits 27% renal elimination, and dabigatran demonstrates predominant renal excretion at 80%. Rivaroxaban and edoxaban also undergo renal elimination, but to a lesser extent, at approximately 35% and 50%, respectively.[13]

Administration

Available Dosage Forms and Strengths

Apixaban is available in the oral formulation as 2.5 mg and 5 mg tablets. Dosing depends on the indication for treatment, the patient's age, serum creatinine, and body weight.

Adult Dosage

  • Patients with DVT and PE are required to take 10 mg twice daily for 7 days, followed by 5 mg twice daily.
  • In the European Union (EU) and by the FDA, apixaban currently holds approval as a prophylactic agent following hip and knee replacement surgeries. The recommended dosage for DVT prophylaxis post-hip or knee replacement surgery is 2.5 mg orally twice daily. It is advised to initiate the dosage 12 to 24 hours post-surgery, with a treatment duration of 12 days for knee replacement and approximately 35 days for hip replacement.[14]
  • The recommended dosage for patients with nonvalvular atrial fibrillation is 5 mg twice daily.[13] However, for patients meeting at least 2 out of 3 criteria below, the dosage of apixaban 5 mg should be reduced to 2.5 mg daily.
    • Age 80 or older
    • Serum creatinine greater than or equal to 1.5 mg/dL
    • Body weight less than or equal to 60 kg

If the dosage is not scheduled, the patient should take the dosage as soon as possible within the same day and resume the twice-daily schedule. However, a double dose is not recommended to compensate for a missing dosage.

Other options for administration: The patients who have difficulty swallowing whole tablets may be able to crush and suspend 2.5 mg and 5 mg of apixaban tablets in water, apple juice, 5% dextrose in water (D5W), or applesauce and administer them orally immediately. These crushed tablets remain stable for up to 4 hours. Alternatively, these tablets may be crushed and suspended in 60 mL of water or D5W for prompt delivery via a nasogastric tube.

Specific Patients Population 

Hepatic impairment: The apixaban dosage instructions for patients with hepatic impairment are listed below.

  • Mild hepatic impairment (Child-Pugh class A): No dosage adjustment is required.
  • Moderate hepatic impairment (Child-Pugh class B): Limited clinical experience in patients with moderate hepatic impairment; hence, any dosing adjustment has yet to be established.
  • Severe hepatic impairment (Child-Pugh class C): Apixaban is not recommended.

Renal impairment: As mentioned above, the recommended apixaban dosage for patients with at least 2 of the following should be reduced from 5 mg to 2.5 mg twice daily.[14]

  • Age 80 or older
  • Serum creatinine greater than or equal to 1.5 mg/dL
  • Body weight less than or equal to 60 kg
  • A study examined apixaban dosing in atrial fibrillation with chronic kidney disease stage 4 or 5. Results demonstrated that 5 mg apixaban was associated with an increased bleeding risk than 2.5 mg dose. No clinically significant differences were apparent in the risk of stroke/systemic embolism or mortality between the 2 dosage groups. These findings support the dosing recommendations based on kidney function. The study underscores the imperative for further investigation in this area, emphasizing the necessity for tailored dosing strategies for patients with chronic kidney disease.[15]
  • Clinical efficacy and safety studies with apixaban did not include patients with end-stage renal disease (ESRD) on dialysis. Therefore, it is not recommended on the drug label as a proven anticoagulant of choice in patients with ESRD. An alternate anticoagulant like warfarin should be considered in patients with ESRD.

Pregnancy considerations: A limited amount of data is available on the use of apixaban tablets in pregnant women and the associated risk of major congenital disabilities, adverse outcomes, or miscarriage. The treatment with the drug may lead to an increased risk of bleeding during pregnancy and delivery. As per the American College of Obstetricians and Gynecologists (ACOG), the use of dabigatran and anti-Xa Inhibitors (such as rivaroxaban, apixaban, and edoxaban) is not recommended during pregnancy due to the limited availability of safety data about the well-being of the mother, fetus, and breastfeeding neonate. Research involving human placental studies has indicated the passage of these inhibitors across the placenta, warranting caution regarding potential indirect effects on fetal blood coagulation.[16]

Breastfeeding considerations: Limited clinical data is available regarding apixaban or its metabolites in human milk. However, studies have shown that apixaban and its metabolites were detected in rat milk. The observed levels of apixaban in breast milk, ranging from 0.2 to 0.25 mg/L, correspond to a relative infant dose of 10% to 21% of the maternal weight-adjusted dosage. Given this significant transfer, it is advisable to consider alternative anticoagulants with lower excretion into breast milk, especially when nursing newborns or preterm infants.[17]

Pediatric patients: The safety and efficacy of apixaban tablets have not been established in pediatric patients. 

Older patients: No clinically significant difference is detected in the safety and efficacy of apixaban when comparing different age groups. The prior American Geriatrics Society (AGS) recommendation emphasized the importance of prudence when considering the use of apixaban in creatinine clearance (CrCl) below 25 mL/min. However, the 2023 AGS update now indicates that emerging evidence and clinical experience support its safe use at lower levels of renal function.[18]

Adverse Effects

As an anticoagulant, apixaban's most common adverse effect is bleeding (1% to 10%). The risk of major bleeding is 3% or less, and clinically relevant nonmajor bleeding is 2% to 4%. Other less common adverse effects include nausea (3%), gingival hemorrhage (1% or less), hematuria (2% or less), hypermenorrhea (1%), anemia (3%), bruise (1% to 2%), hematoma (1% to 2%), postprocedural hemorrhage (1% or less), rectal hemorrhage (1% or less), increased serum transaminases (1% or less), aspartate aminotransferase increased (1% or less), gamma-glutamyltransferase increased (1% or less), epistaxis (4% or less), and hemoptysis (1% or less). In rare instances (less than 1%), it can cause a hypersensitivity reaction.

According to the FDA, apixaban is not recommended for patients with prosthetic heart valves.[19]

Drug-Drug Interactions

Most apixaban drug interactions are associated with CYP3A4 and permeability glycoprotein (P-gp), as apixaban is a substrate for both. The drugs that inhibit CYP3A4 and P-gp may increase the exposure of apixaban and the associated risk of bleeding. On the contrary, drugs that induce CYP3A4 and P-gp may decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events.[20][21]

Coadministration of apixaban and P-gp strong CYP3A4 inhibitors: Suppose patients receive apixaban 5 or 10 mg twice daily. In that case, it is recommended to decrease the dose of apixaban by 50% for patients who are also receiving P-gp and potent CYP3A4-inhibiting drugs such as ritonavir, ketoconazole, and itraconazole. However, if patients receive apixaban 2.5 mg twice daily, it is recommended to avoid coadministration for patients who also receive P-gp and potent CYP3A4 inhibitors. 

Coadministration of apixaban and P-gp strong CYP3A4 inducers: Coadministration of apixaban with other P-gp and strong CYP3A4-inducing drugs, such as phenytoin, carbamazepine, and rifampin, should be avoided, as these drugs may decrease the exposure to apixaban.

Coadministration of apixaban with other anticoagulants and antiplatelet agents: When apixaban is coadministered with other anticoagulants and antiplatelet agents, such as heparin, aspirin, and chronic nonsteroidal anti-inflammatory drugs (NSAIDs), it may increase the risk of bleeding.

Contraindications

Per the manufacturer's label, active pathological bleeding and severe hypersensitivity reaction to apixaban, for example, an anaphylactic reaction, are the contraindications to using apixaban.[22]

Box Warnings

Thrombotic events: Premature discontinuation of oral anticoagulant medicines, including apixaban, can increase the risk of thrombotic adverse events. In cases where discontinuation of apixaban is necessary, it is advisable to provide alternative anticoagulant coverage.

Spinal/epidural hematoma: Clinicians should monitor patients frequently for signs and symptoms of neurological impairment. Urgent treatment is necessary if neurological compromise is noted. When considering the utilization of apixaban, it is essential to evaluate potential interactions with other drugs that impact hemostasis, such as NSAIDs and alternative anticoagulants.

During neuraxial anesthesia or spinal puncture, careful scheduling and risk assessment are imperative due to the potential for hematomas. Therefore, a thorough assessment of the patient's medical history is crucial, particularly focusing on any prior instances of traumatic or repeated epidural or spinal punctures. Furthermore, special attention should be given to individuals with a history of spinal deformity or previous spinal surgery. The optimal timing for administering apixaban during neuraxial procedures remains uncertain.

The American Society of Regional Anesthesia & Pain Medicine (ASRA) issues specific recommendations to mitigate the potential risk of spinal hematoma due to apixaban during pain procedures. ASRA advises a precautionary waiting period equivalent to 5 half-lives, or approximately 3 days, between discontinuation of apixaban and medium- or high-risk pain procedures. For low-risk procedures, a collaborative assessment, risk stratification, and decision-making process involving the attending physicians should determine whether discontinuing apixaban is warranted. In such situations, a shorter interval of 2 half-lives may be considered. ASRA recommends a 24-hour interval after interventional pain procedures before resuming apixaban. In cases where the risk of VTE remains notably high, administering half the standard dose may be a viable option 12 hours after the pain intervention.[23]

Monitoring

Unlike warfarin, apixaban does not need monitoring of the patient's international normalized ratio (INR), offering an advantage.[24] Patients on warfarin must get their INR checked every week, 2 weeks, or 4 weeks, depending on the control, whereas patients using apixaban do not need any blood draws; this improves patient adherence.[25][26]

The most significant adverse effect is bleeding. Therefore, concomitant use of drugs affecting hemostasis, including antiplatelets, other anticoagulants, thrombolytic agents, NSAIDs, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs), should be reasonable. The elimination half-life is about 12 hours (8 to 15 hours). Before a patient undergoes elective surgery or an invasive procedure, the drug should be held for 48 hours if the procedure is a moderate-high risk with clinically significant bleeding. For procedures with a low risk of bleeding, it should be held 24 hours before the procedure. Bridging anticoagulation 24 to 48 hours after is not usually recommended.[27] Furthermore, the drug must be restarted following surgical or other procedures after establishing adequate hemostasis.

Toxicity

In May 2018, the FDA approved the first antidote for reversing factor Xa inhibitors called andexanet alfa. Andexanet alfa is a biological agent—a modified recombinant derivative of factor Xa that acts as a decoy receptor. It has a higher affinity for factor Xa inhibitor than natural Xa; consequently, the inhibitor binds to the drug rather than to natural Xa itself. It received the US Orphan Drug and FDA Breakthrough Therapy designations. Due to its recent approval, limited real-world data is available on the use of this antidote. Further research will determine its efficacy and safety profile in the future.[28] 

Prothrombin complex concentrates (PCCs) are a mixture of factors II, IX, and X. Some PCCs include factor VII. Since the 1960s, it has been known to reverse laboratory measures and bleeding from factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban in healthy volunteers, animal models, and in vitro studies of healthy donor blood. One institution instituted a protocol of administering 4-factor PCC for patients with rivaroxaban-associated or apixaban-associated bleeding requiring immediate reversal. However, whether this strategy results in clinical improvements for such patients has yet to be determined.[28]

Ciraparantag, an investigational therapy, demonstrates a dose-dependent reversal of anticoagulation from steady-state apixaban or rivaroxaban treatment. However, it is important to emphasize that ciraparantag is not yet FDA-approved, stressing the necessity for further research and evaluation, particularly in toxicity.[29]

Enhancing Healthcare Team Outcomes

All interprofessional healthcare team members, including clinicians, specialists (cardiologists, internists, hospitalists, hematologists, and others), nursing staff, and pharmacists who treat patients with atrial fibrillation should be well informed regarding pharmacotherapy with apixaban. The FDA approved this NOAC for use in patients with nonvalvular atrial fibrillation to reduce the risk of stroke and blood clots, and it was later approved to treat DVT and PE. In 2014, the drug was also FDA-approved to reduce the risk of blood clots (DVT and PE) in patients following knee and hip replacement surgery.[30] A study examined the role of pharmacists within the interprofessional healthcare team. Implementing a pharmacist-driven DOAC protocol (pre-intervention and post-intervention) reduced the percentage of inappropriately administered DOACs, including apixaban, highlighting the vital contribution of pharmacists in optimizing anticoagulant therapy and preventing potential adverse events.[31]

Unlike warfarin, the drug is relatively safe and does not need INR monitoring. However, ongoing close monitoring of patients taking apixaban is necessary to prevent bleeding; to this end, all clinicians, nurses, and pharmacists should counsel the patient so they are aware of the early signs of potential bleeding that could lead to more severe events. If an overdose occurs, immediate action is necessary, including consultation with a hematologist. A critical care physician should supervise appropriate medical management in the medical intensive care unit. If any healthcare team member detects signs of bleeding, it is imperative to promptly communicate this to the prescriber to facilitate timely therapeutic intervention. Collaboratively, the interprofessional team must operate as a cohesive unit to ensure the safety and efficacy of apixaban treatment for their patients, ultimately aiming for optimal patient outcomes while minimizing adverse events.

References


[1]

Skelley JW, Thomason AR, Hammond LN. Extended-Duration Use of Direct Oral Anticoagulants to Prevent VTE in Acutely III Medical Patients. The Senior care pharmacist. 2019 Feb 1:34(2):99-108. doi: 10.4140/TCP.n.2019.99. Epub     [PubMed PMID: 30821668]


[2]

Powell J, Taylor J, Garland SG. Andexanet alfa: A Novel Factor Xa Inhibitor Reversal Agent. The Annals of pharmacotherapy. 2019 Sep:53(9):940-946. doi: 10.1177/1060028019835209. Epub 2019 Feb 27     [PubMed PMID: 30813754]


[3]

Knotts TL, Mousa SA. Anticoagulation in Venous Thromboembolism Prophylaxis in Medically Ill Patients: Potential Impact of NOACs. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2019 Aug:19(4):365-376. doi: 10.1007/s40256-019-00329-5. Epub     [PubMed PMID: 30809772]


[4]

January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019 Jul 9:140(2):e125-e151. doi: 10.1161/CIR.0000000000000665. Epub 2019 Jan 28     [PubMed PMID: 30686041]

Level 1 (high-level) evidence

[5]

Barrett YC, Wang J, Knabb R, Mohan P. Apixaban decreases coagulation activity in patients with acute deep-vein thrombosis. Thrombosis and haemostasis. 2011 Jan:105(1):181-9. doi: 10.1160/TH10-06-0393. Epub 2010 Oct 12     [PubMed PMID: 20941459]

Level 1 (high-level) evidence

[6]

Lai J, Feng S, Xu S, Liu X. Effects of oral anticoagulant therapy in patients with pulmonary diseases. Frontiers in cardiovascular medicine. 2022:9():987652. doi: 10.3389/fcvm.2022.987652. Epub 2022 Aug 10     [PubMed PMID: 36035947]


[7]

Weitz JI, Chan NC. Long-Term Management of Venous Thromboembolism: Lessons from EINSTEIN CHOICE and Other Extension Trials. Thrombosis and haemostasis. 2019 May:119(5):689-694. doi: 10.1055/s-0039-1679906. Epub 2019 Feb 26     [PubMed PMID: 30808045]


[8]

Young M. Atrial Fibrillation. Critical care nursing clinics of North America. 2019 Mar:31(1):77-90. doi: 10.1016/j.cnc.2018.11.005. Epub     [PubMed PMID: 30736937]


[9]

Bikdeli B, Hogan H, Morrison RB, Fanikos J, Campia U, Barns BM, Pfeferman MB, Snyder JE, Khairani CD, Goldhaber SZ, Piazza G. Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in Patients with Provoked Venous Thromboembolism and Enduring Risk Factors: Rationale and Design of the HI-PRO Trial. Thrombosis and haemostasis. 2022 Jun:122(6):1061-1070. doi: 10.1055/a-1646-2244. Epub 2021 Oct 31     [PubMed PMID: 34530470]


[10]

Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, Linkins LA, Rodner SB, Selleng S, Warkentin TE, Wex A, Mustafa RA, Morgan RL, Santesso N. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood advances. 2018 Nov 27:2(22):3360-3392. doi: 10.1182/bloodadvances.2018024489. Epub     [PubMed PMID: 30482768]

Level 3 (low-level) evidence

[11]

Frost C, Wang J, Nepal S, Schuster A, Barrett YC, Mosqueda-Garcia R, Reeves RA, LaCreta F. Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. British journal of clinical pharmacology. 2013 Feb:75(2):476-87. doi: 10.1111/j.1365-2125.2012.04369.x. Epub     [PubMed PMID: 22759198]

Level 1 (high-level) evidence

[12]

Byon W, Garonzik S, Boyd RA, Frost CE. Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review. Clinical pharmacokinetics. 2019 Oct:58(10):1265-1279. doi: 10.1007/s40262-019-00775-z. Epub     [PubMed PMID: 31089975]


[13]

Yao X, Inselman JW, Ross JS, Izem R, Graham DJ, Martin DB, Thompson AM, Ross Southworth M, Siontis KC, Ngufor CG, Nath KA, Desai NR, Nallamothu BK, Saran R, Shah ND, Noseworthy PA. Comparative Effectiveness and Safety of Oral Anticoagulants Across Kidney Function in Patients With Atrial Fibrillation. Circulation. Cardiovascular quality and outcomes. 2020 Oct:13(10):e006515. doi: 10.1161/CIRCOUTCOMES.120.006515. Epub 2020 Oct 5     [PubMed PMID: 33012172]

Level 2 (mid-level) evidence

[14]

Rooney T, Barrack RL, Clohisy JC, Nunley RM, Lawrie CM. Is Apixaban Safe and Effective for Venous Thromboembolism Prophylaxis After Primary Total Hip and Total Knee Arthroplasties? The Journal of arthroplasty. 2021 Jul:36(7S):S328-S331. doi: 10.1016/j.arth.2021.03.030. Epub 2021 Mar 23     [PubMed PMID: 33888386]


[15]

Xu Y, Chang AR, Inker LA, McAdams-DeMarco M, Grams ME, Shin JI. Associations of Apixaban Dose With Safety and Effectiveness Outcomes in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease. Circulation. 2023 Nov 7:148(19):1445-1454. doi: 10.1161/CIRCULATIONAHA.123.065614. Epub 2023 Sep 8     [PubMed PMID: 37681341]


[16]

American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy. Obstetrics and gynecology. 2018 Jul:132(1):e1-e17. doi: 10.1097/AOG.0000000000002706. Epub     [PubMed PMID: 29939938]


[17]

. Apixaban. Drugs and Lactation Database (LactMed®). 2006:():     [PubMed PMID: 29999800]


[18]

By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023 Jul:71(7):2052-2081. doi: 10.1111/jgs.18372. Epub 2023 May 4     [PubMed PMID: 37139824]


[19]

Langenaeken T, Vanoppen A, Janssens F, Tanghe L, Verbrugghe P, Rega F, Meuris B. DOACs in the Anticoagulation of Mechanical Valves: A Systematic Review and Future Perspectives. Journal of clinical medicine. 2023 Jul 28:12(15):. doi: 10.3390/jcm12154984. Epub 2023 Jul 28     [PubMed PMID: 37568386]

Level 1 (high-level) evidence

[20]

Kubisz P, Stanciakova L, Dobrotova M, Samos M, Mokan M, Stasko J. Apixaban - Metabolism, Pharmacologic Properties and Drug Interactions. Current drug metabolism. 2017:18(7):609-621. doi: 10.2174/1389200218666170424151551. Epub     [PubMed PMID: 28440204]


[21]

Ammar H, Govindu RR. A Dangerous and Unrecognized Interaction of Apixaban. Cureus. 2021 Nov:13(11):e19688. doi: 10.7759/cureus.19688. Epub 2021 Nov 18     [PubMed PMID: 34934565]


[22]

Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management. World journal of gastroenterology. 2017 Mar 21:23(11):1954-1963. doi: 10.3748/wjg.v23.i11.1954. Epub     [PubMed PMID: 28373761]


[23]

Narouze S, Benzon HT, Provenzano D, Buvanendran A, De Andres J, Deer T, Rauck R, Huntoon MA. Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications (Second Edition): Guidelines From the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain. Regional anesthesia and pain medicine. 2018 Apr:43(3):225-262. doi: 10.1097/AAP.0000000000000700. Epub     [PubMed PMID: 29278603]


[24]

Conway SE, Hwang AY, Ponte CD, Gums JG. Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know. Pharmacotherapy. 2017 Feb:37(2):236-248. doi: 10.1002/phar.1884. Epub 2017 Feb 3     [PubMed PMID: 27983747]


[25]

Kajy M, Shokr M, Ramappa P. Use of Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombus: Systematic Review of Current Literature. American journal of therapeutics. 2020 Nov/Dec:27(6):e584-e590. doi: 10.1097/MJT.0000000000000937. Epub     [PubMed PMID: 30730331]

Level 1 (high-level) evidence

[26]

Gressenberger P. Reversal strategies in patients treated with direct oral anticoagulants. VASA. Zeitschrift fur Gefasskrankheiten. 2019 Aug:48(5):389-392. doi: 10.1024/0301-1526/a000777. Epub 2019 Feb 5     [PubMed PMID: 30719950]


[27]

Kaye AD, Manchikanti L, Novitch MB, Mungrue IN, Anwar M, Jones MR, Helander EM, Cornett EM, Eng MR, Grider JS, Harned ME, Benyamin RM, Swicegood JR, Simopoulos TT, Abdi S, Urman RD, Deer TR, Bakhit C, Sanapati M, Atluri S, Pasupuleti R, Soin A, Diwan S, Vallejo R, Candido KD, Knezevic NN, Beall D, Albers SL, Latchaw RE, Prabhakar H, Hirsch JA. Responsible, Safe, and Effective Use of Antithrombotics and Anticoagulants in Patients Undergoing Interventional Techniques: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Pain physician. 2019 Jan:22(1S):S75-S128     [PubMed PMID: 30717501]


[28]

Liss DB, Mullins ME. Antithrombotic and Antiplatelet Drug Toxicity. Critical care clinics. 2021 Jul:37(3):591-604. doi: 10.1016/j.ccc.2021.03.012. Epub     [PubMed PMID: 34053708]


[29]

Ansell J, Bakhru S, Laulicht BE, Tracey G, Villano S, Freedman D. Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects. European heart journal. 2022 Mar 7:43(10):985-992. doi: 10.1093/eurheartj/ehab637. Epub     [PubMed PMID: 34534272]


[30]

Coleman CI, Briere JB, Fauchier L, Levy P, Bowrin K, Toumi M, Millier A, Taieb V, Wu O. Meta-analysis of real-world evidence comparing non-vitamin K antagonist oral anticoagulants with vitamin K antagonists for the treatment of patients with non-valvular atrial fibrillation. Journal of market access & health policy. 2019:7(1):1574541. doi: 10.1080/20016689.2019.1574541. Epub 2019 Feb 4     [PubMed PMID: 30774786]

Level 1 (high-level) evidence

[31]

Miele C, Taylor M, Shah A. Assessment of Direct Oral Anticoagulant Prescribing and Monitoring Pre- and Post-Implementation of a Pharmacy Protocol at a Community Teaching Hospital. Hospital pharmacy. 2017 Mar:52(3):207-213. doi: 10.1310/hpj5203-207. Epub     [PubMed PMID: 28439135]