INDICATION

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ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF).

ELIQUIS is indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and to reduce the risk of recurrent DVT and PE following initial therapy.

ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery.

This site is intended for U.S. formulary decision-makers

ELIQUIS Evidence

ELIQUIS was studied in 7 registrational RCTs, including 18,201 patients in ARISTOTLE and 5598 patients in AVERROES. ELIQUIS has clinical information from registrational trials as well as real-world data that provide additional information using a national sample of Medicare and commercial claims data.1-4 A few of these are included below. For more information, use the Request More Information form.

Select Randomized Clinical Trials

Stroke/Systemic Embolism
Risk Reduction in NVAF

ARISTOTLE (18,201 patients) and
AVERROES (5598 patients)

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U.S. FULL PRESCRIBING INFORMATION

Treatment of VTE and Reduction of Risk of Recurrence Following Initial Treatment

AMPLIFY (5400 patients) and
AMPLIFY-EXT (1671 patients)

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U.S. FULL PRESCRIBING INFORMATION

Select Real-World Evidence

Effectiveness and Safety: NVAF Analyses (with RCT data)

CMS analysis† (77,480 patients)
(Medicare Advantage)

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U.S. FULL PRESCRIBING INFORMATION

American Journal of Managed
Care article†
(Pooled Medicare Advantage
and Commercial)
This article was developed and
paid for by
BMS and Pfizer.

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U.S. FULL PRESCRIBING INFORMATION

Effectiveness and Safety: VTE Analyses (with RCT data)

Pooled analysis† (35,756 patients)
(Medicare Advantage and Commercial)

DOWNLOAD
U.S. FULL PRESCRIBING INFORMATION

†Real-world analysis was sponsored by Bristol Myers Squibb and Pfizer Inc.

CMS=Centers for Medicare & Medicaid Services; NVAF=nonvalvular atrial fibrillation; RCTs=randomized controlled trials; VTE=venous thromboembolism.

SELECT IMPORTANT SAFETY INFORMATION

WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA

(A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

(B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

  • use of indwelling epidural catheters
  • concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
  • a history of traumatic or repeated epidural or spinal punctures
  • a history of spinal deformity or spinal surgery
  • optimal timing between the administration of ELIQUIS and neuraxial procedures is not known

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.

CONTRAINDICATIONS

  • Active pathological bleeding
  • Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)
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To learn about additional ELIQUIS RCT and RWE data, please reach out to an Account Director

Request more information

Frequently Asked
Questions

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  • Examples of databases used in some select manufacturer-sponsored real-world effectiveness and safety analyses include the Centers for Medicare & Medicaid Services (CMS) database and the OptumLabs® Data Warehouse2,4*
    • These databases are large-scale, third-party databases, and they provide a diverse geographic representation of claims from health plans and government organizations4-6

    • *Optum® is a registered trademark of Optum, Inc.

  • Baseline covariates in ELIQUIS manufacturer-sponsored real-world effectiveness and safety analyses are adjusted for using PS matching and/or IPTW3,4,7,8

    • IPTW=inverse probability treatment weighting; PS=propensity score.

  • Regression analysis is a common methodology used to describe the relationship between a set of independent variables (eg, the treatment being used) and a dependent variable (eg, clinical outcomes such as rate of bleeds or frequency of adverse events)9
    • A Cox proportional hazards regression model is a regression method that uses time-to-event data to generate hazard ratios by analyzing the association between a specified event and 1 or more predictor variables10,11

    • DVT/PE=deep vein thrombosis/pulmonary embolism.

  • Examples of outcomes from ELIQUIS manufacturer-sponsored real-world effectiveness and safety analyses include:
    • The rate of stroke/systemic embolism and major bleeding outcomes associated with select direct oral anticoagulants (including ELIQUIS) compared with warfarin in patients with nonvalvular atrial fibrillation (NVAF) and oral anticoagulant treatment-naïve patients with NVAF12
    • The effectiveness (recurrent VTE) and bleeding (major and CRNM) outcomes associated with ELIQUIS vs warfarin for acute or outpatient treatment of venous thromboembolism7

    • ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding.1

    CRNM=clinically relevant non-major; RWD=real-world data; VTE=venous thromboembolism.

  • Examples of peer-reviewed comparative effectiveness research guidance used in ELIQUIS manufacturer-sponsored real-world effectiveness and safety analyses include:
    • International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Good Research Practices for Retrospective Database Analysis Task Force Report—Parts I, II, and III13-15
    • Journal of Managed Care & Specialty Pharmacy (JMCP) “Ten Commandments” for Conducting Comparative Effectiveness Research Using “Real-World Data”16

    • RWD=real-world data.

IMPORTANT SAFETY INFORMATION

WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS,
(B) SPINAL/EPIDURAL HEMATOMA

(A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

(B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

  • use of indwelling epidural catheters
  • concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
  • a history of traumatic or repeated epidural or spinal punctures
  • a history of spinal deformity or spinal surgery
  • optimal timing between the administration of ELIQUIS and neuraxial procedures is not known

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.

CONTRAINDICATIONS

  • Active pathological bleeding
  • Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)

WARNINGS AND PRECAUTIONS

  • Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including ELIQUIS, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
  • Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding.
    • Concomitant use of drugs affecting hemostasis increases the risk of bleeding, including aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs.
    • Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
    • The anticoagulant effect of apixaban can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). An agent to reverse the anti-factor Xa activity of apixaban is available. Please visit www.andexxa.comwww.andexxa.com for more information on availability of a reversal agent.
  • Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis.
    The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours.
    Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in ELIQUIS patients.
  • Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients.
  • Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.
  • Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome (APS): Direct-acting oral anticoagulants (DOACs), including ELIQUIS, are not recommended for use in patients with triple-positive APS. For patients with APS (especially those who are triple positive [positive for lupus anticoagulant, anticardiolipin, and anti–beta 2-glycoprotein I antibodies]), treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.

ADVERSE REACTIONS

  • The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding.

TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS

  • ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established.

DRUG INTERACTIONS

  • Combined P-gp and Strong CYP3A4 Inhibitors: Inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when ELIQUIS is coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or ritonavir). In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors.
    Clarithromycin
    Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS.
  • Combined P-gp and Strong CYP3A4 Inducers: Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban.
  • Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.

PREGNANCY

  • The limited available data on ELIQUIS use in pregnant women are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse developmental outcomes. Treatment may increase the risk of bleeding during pregnancy and delivery, and in the fetus and neonate.
    • Labor or delivery : ELIQUIS use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. Consider use of a shorter acting anticoagulant as delivery approaches.

LACTATION

  • Breastfeeding is not recommended during treatment with ELIQUIS.

FEMALES AND MALES OF REPRODUCTIVE POTENTIAL

  • Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including ELIQUIS should be assessed in these patients and those with abnormal uterine bleeding.

INDICATIONS

ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery.

ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy.

Please see U.S. FULL PRESCRIBING INFORMATION, including Boxed WARNINGS, and MEDICATION GUIDE.

ELIQUIS is available in 2.5 mg and 5 mg tablets.

References

1. ELIQUIS® (apixaban) Package Insert. Bristol-Myers Squibb Company, Princeton, NJ, and Pfizer Inc, New York, NY.

2. Lip GYH, Keshishian A, Li X, et al. Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients [published correction appears in Stroke. 2020;51:e71. doi:10.0061/STR0000000000000227 and Stroke. 2020;51:e44. doi:10.00161/STR0000000000000218]. Stroke. 2018;49:2933-2944. doi:10.0061/STROKEAHA.118.020232

3. Yao X, Abraham NS, Sangaralingham LR, et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc. 2016;5(6):1-18. pii: e003725. doi:10.1161/JAHA.116.003725

4. Amin A, Keshishian A, Trocio J, et al. Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population. Curr Med Res Opin. 2017;33(9):1595-1604. doi:10.1080/03007995.2017.1345729

5. About OptumLabs and UC Health Partnership. UC Davis Health Clinical and Translational Science Center. https://health.ucdavis.edu/ctsc/area/Resource_Library/optum_uchealth.html. Accessed July 26, 2021.

6. Finding datasets for secondary analysis. Johns Hopkins University of Medicine. Updated July 26, 2021. https://browse.welch.jhmi.edu/datasets/medicare-data. Accessed July 26, 2021.

7. Weycker D, Li X, Wygant GD, et al. Effectiveness and safety of apixaban versus warfarin as outpatient treatment of venous thromboembolism in U.S. clinical practice. J Thromb Haemost. 2018;118(11):1951-1961. doi:10.1055/s-0038-1673689

8. Lip GYH, Keshishian AV, Kang AL, et al. Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study. J Intern Med. 2021;289:42-52. doi:10.1111/joim.13140

9. Anderson RP, Jin R, Grunkemeier GL. Understanding logistic regression analysis in clinical reports: an introduction. Ann Thorac Surg. 2003;75:753-757. doi:10.1016/s0003-4975(02)04683-0

10. White SE. Glossary. Basic & Clinical Biostatistics. 5th ed. McGraw-Hill Education; 2020.

11. StatsDirect. Cox (proportional hazards) regression.
https://www.statsdirect.com/help/Default.htm#survival_analysis/cox_regression.htm. Accessed March 8, 2021.

12. Data on file: APIX 050. Bristol-Myers Squibb Company, Princeton, NJ.

13. Cox E, Martin BC, Van Staa T, Garbe E, Siebert U, Johnson ML. Good research practices for comparative effectiveness research: approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: The International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective Database Analysis Task Force Report—Part II. Value Health.
2009;12(8):1053-1061. doi:10.1111/j.1524-4733.2009.00601

14. Berger ML, Mamdani M, Atkins D, Johnson ML. Good research practices for comparative effectiveness research: defining, reporting and interpreting nonrandomized studies of treatment effects using secondary data sources: The ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report—Part I. Value Health. 2009;12(8):1044-1052. doi:10.1111/j.1524-4733.2009.00600.x. Epub 2009 Sep 29.

15. Johnson ML, Crown W, Martin BC, Dormuth CR, Siebert U. Good research practices for comparative effectiveness research: analytic methods to improve causal inference from nonrandomized studies of treatment effects using secondary data sources: The ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report—Part III. Value Health. 2009;12(8):1062-1073.

16. Willke RJ, Mullins CD. “Ten commandments” for conducting comparative effectiveness research using “real-world data.” J Manage Care Pharm. 2011;17(9 Suppl A):S10-S15.

ELIQUIS® and the ELIQUIS logo are trademarks of
Bristol-Myers Squibb Company.
All other trademarks are the property of their respective owners.

© 2022 Bristol-Myers Squibb Company.
432-US-2200332 08/22

References

1. ELIQUIS® (apixaban) Package Insert. Bristol-Myers Squibb Company, Princeton, NJ, and Pfizer Inc, New York, NY.

2. Lip GYH, Keshishian A, Li X, et al. Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients [published correction appears in Stroke. 2020;51:e71. doi:10.0061/STR0000000000000227 and Stroke. 2020;51:e44. doi:10.00161/STR0000000000000218]. Stroke. 2018;49:2933-2944. doi:10.0061/STROKEAHA.118.020232

3. Yao X, Abraham NS, Sangaralingham LR, et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc. 2016;5(6):1-18. pii: e003725. doi:10.1161/JAHA.116.003725

4. Amin A, Keshishian A, Trocio J, et al. Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population. Curr Med Res Opin. 2017;33(9):1595-1604. doi:10.1080/03007995.2017.1345729

5. About OptumLabs and UC Health Partnership. UC Davis Health Clinical and Translational Science Center. https://health.ucdavis.edu/ctsc/area/Resource_Library/optum_uchealth.html. Accessed July 26, 2021.

6. Finding datasets for secondary analysis. Johns Hopkins University of Medicine. Updated July 26, 2021. https://browse.welch.jhmi.edu/datasets/medicare-data. Accessed July 26, 2021.

7. Weycker D, Li X, Wygant GD, et al. Effectiveness and safety of apixaban versus warfarin as outpatient treatment of venous thromboembolism in U.S. clinical practice. J Thromb Haemost. 2018;118(11):1951-1961. doi:10.1055/s-0038-1673689

8. Lip GYH, Keshishian AV, Kang AL, et al. Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study. J Intern Med. 2021;289:42-52. doi:10.1111/joim.13140

9. Anderson RP, Jin R, Grunkemeier GL. Understanding logistic regression analysis in clinical reports: an introduction. Ann Thorac Surg. 2003;75:753-757. doi:10.1016/s0003-4975(02)04683-0

10. White SE. Glossary. Basic & Clinical Biostatistics. 5th ed. McGraw-Hill Education; 2020.

11. StatsDirect. Cox (proportional hazards) regression.
https://www.statsdirect.com/help/Default.htm#survival_analysis/cox_regression.htm. Accessed March 8, 2021.

12. Data on file: APIX 050. Bristol-Myers Squibb Company, Princeton, NJ.

13. Cox E, Martin BC, Van Staa T, Garbe E, Siebert U, Johnson ML. Good research practices for comparative effectiveness research: approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: The International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective Database Analysis Task Force Report—Part II. Value Health.
2009;12(8):1053-1061. doi:10.1111/j.1524-4733.2009.00601

14. Berger ML, Mamdani M, Atkins D, Johnson ML. Good research practices for comparative effectiveness research: defining, reporting and interpreting nonrandomized studies of treatment effects using secondary data sources: The ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report—Part I. Value Health. 2009;12(8):1044-1052. doi:10.1111/j.1524-4733.2009.00600.x. Epub 2009 Sep 29.

15. Johnson ML, Crown W, Martin BC, Dormuth CR, Siebert U. Good research practices for comparative effectiveness research: analytic methods to improve causal inference from nonrandomized studies of treatment effects using secondary data sources: The ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report—Part III. Value Health. 2009;12(8):1062-1073.

16. Willke RJ, Mullins CD. “Ten commandments” for conducting comparative effectiveness research using “real-world data.” J Manage Care Pharm. 2011;17(9 Suppl A):S10-S15.