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Read our disclaimer for details. Last Update Posted : January 14, See Contacts and Locations. Study Description. Currently, warfarin is the only approved anticoagulation for patients with mechanical valves.
Detailed Description:. There is an unmet clinical need for an alternative to warfarin, such as a direct oral anticoagulant DOAC , as anticoagulation in participants with an aortic mechanical prosthetic valve.
Some participants may be genetically hyper- or hypo-responsive to warfarin, which makes management difficult. Another small group of participants is allergic to warfarin. A much larger group of participants has difficulty maintaining warfarin control due to dietary and drug interactions. Finally, the requirement for routine blood testing makes people reluctant to take warfarin. All of these factors drive younger participants in need of aortic valve replacement AVR toward selection of a tissue valve instead of a mechanical valve.
Despite multiple studies randomized, matched and risk adjusted that show that tissue valves are associated with worse outcomes, younger participants choose this type of valve to avoid warfarin. In addition, multiple clinical studies have shown valve reoperation rates are higher for tissue valves used in these younger participants. Providing an alternative to warfarin anticoagulation may lead younger participants to choose a mechanical valve with greater durability and better clinical outcomes.
MedlinePlus related topics: Blood Thinners. Drug Information available for: Warfarin Warfarin sodium Apixaban. FDA Resources. Arms and Interventions. Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months 90 days ago.
Patients randomized to the warfarin arm will continue warfarin in the INR range of 2. Outcome Measures. To determine if apixaban provides acceptable anticoagulation for patients with an On-X mechanical heart valve implanted in the aortic position for the primary composite outcome of valve thrombosis and valve-related thromboembolism compared with an objective performance criterion. To determine if apixaban is superior to warfarin INR target range 2.
Secondary Outcome Measures : Number of valve-related thrombotic events superiority [ Time Frame: 2 years ] To determine if apixaban is superior to warfarin INR target range 2. To compare apixaban with warfarin INR target range 2. Eligibility Criteria. Inclusion Criteria: Male or female at least 18 years of age at the time of giving informed consent.
Participants currently receiving warfarin anticoagulation and who are able to receive warfarin with a target INR 2. Participants are able to take low-dose aspirin at a dose of 75 mg daily or have a documented contraindication to aspirin use. Implantation of an On-X mechanical valve in the aortic position at least 3 months 90 days ago.
Female participants of childbearing potential, including those who are less than 2 years post-menopausal, must agree to, and comply with using a highly effective method of birth control eg, barrier contraceptives [condom or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices or sexual abstinence while partaking in this study.
In addition, all women of childbearing potential must agree to continue to use birth control throughout the study until last study visit. Informed of the full nature and purpose of the study, including possible risks and side effects, given ample time and opportunity to read and understand this information, and sign and date the written informed consent before inclusion in the study.
Exclusion Criteria: Mechanical valve in any position other than aortic valve. Any cardiac surgery in the three months 90 days prior to enrollment. Known hypersensitivity or other contraindication to apixaban. Ischemic stroke or intracranial hemorrhage within 3 months. Active pathological bleeding at the time of screening for enrollment.
Active endocarditis at the time of screening for enrollment. Pregnant, plan to become pregnant, or are breast feeding. History of non-compliance with recommended monthly INR testing. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials. You are being redirected to a Pfizer corporate site. For your convenience, specialized Bristol Myers Squibb representatives are available by phone or email to help you with your medical, technical, or general inquiries.
Click here to see Co-pay Card patient eligibility requirements and terms of use. Other restrictions may apply. Patient is responsible for applicable taxes, if any. Patients, pharmacists, and prescribers cannot seek reimbursement, from health insurance or any third party, for any part of the benefit received by the patient through this offer.
Your acceptance of this offer confirms that this offer is consistent with your insurance and that you will report the value received as may be required by your insurance provider. Card must be activated before use. Activation and first use of the Co-pay Card must take place by December 31, Card expires 24 months from activation. Upon expiration, eligible patients may re-enroll in the Co-pay Card Program. All Program payments are for the benefit of the patient only. Only valid in the United States and Puerto Rico; this offer is void where restricted or prohibited by law.
The Co-pay Card may not be sold, purchased, traded, or counterfeited. Reproductions of this Co-pay Card are void. Bristol Myers Squibb and Pfizer reserve the right to rescind, revoke, or amend this offer at any time without notice.
This offer is not conditioned on any past, present, or future purchase, including refills. No membership fees. Click here to see Free Trial Offer, patient eligibility requirements and terms of use. This offer may not be redeemed on prescriptions written for longer than 30 days. Published online May Boyd , 1 and Charles E. Frost 2. Rebecca A. Author information Copyright and License information Disclaimer.
Wonkyung Byon, Phone: , Email: moc. Corresponding author. This article has been cited by other articles in PMC. Abstract Apixaban is an oral, direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa, and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non-valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism.
Key Points Apixaban, a direct factor Xa inhibitor, has predictable pharmacokinetic and pharmacodynamic properties that are consistent across a wide range of patients, including the elderly and those with moderate renal impairment. The fast onset of action, low potential for food or drug interactions, and lack of requirement for routine monitoring during clinical use make apixaban a potentially useful option to simplify anticoagulation treatment.
Open in a separate window. Introduction Warfarin and other vitamin K antagonists VKAs are highly effective oral anticoagulants but are limited by a narrow therapeutic window, drug and food interactions, and the requirement for frequent monitoring [ 1 , 2 ].
Chemical and Physicochemical Properties Apixaban, 1- 4-methoxyphenyl oxo 4- 2-oxopiperidinyl phenyl -4,5,6,7-tetrahydro-1 H -pyrazolo[3,4- c ]pyridinecarboxamide Fig. Pharmacokinetic Properties A summary of the absorption, distribution, metabolism, and elimination of apixaban is shown in Fig. Table 1 Apixaban pharmacokinetic parameters following a single-dose administration [ 17 ] Reproduced with premission from Frost et al.
Table 2 Apixaban pharmacokinetic parameters following a single- and multiple-dose days 1 and 7 administration [ 21 ] Reproduced with permission from Frost et al. Absorption, Bioavailability, and Biopharmaceutical Profile The maximum plasma concentration C max of apixaban occurs 3—4 h after oral administration [ 17 , 21 ].
Pharmacokinetic Effects of Intrinsic Factors in Special Populations The effects of intrinsic factors on the pharmacokinetics of apixaban from phase I studies in special populations are described below, and selected results are summarized in Fig. Race In healthy subjects, pharmacokinetics in Asian Japanese and Chinese subjects were similar to pharmacokinetics in non-Asian subjects [ 34 — 36 ]. Pediatric Population Limited PK data are available from a multiple-dose PK study of apixaban using an oral solution 0.
Drug Interactions Effects of Apixaban on the Pharmacokinetics of Other Drugs In vitro assessment showed that apixaban did not induce or inhibit major CYP enzymes or interfere with transport of P-gp substrates [ 25 ]. Pharmacodynamic Properties The PD effects of apixaban observed in clinical studies were consistent with its mechanism of action: direct reversible inhibition of FXa. Table 3 Predicted apixaban steady-state maximum plasma concentration C max and minimum plasma concentration C min and factor Xa anti-FXa activity in approved indications [ 40 — 42 ] Reproduced with permission from the European Union summary of product characteristics: Eliquis apixaban tablets ; and from Byon et al.
Pharmacodynamic Interactions with Anticoagulants and Antiplatelet Agents After combined administration of LMWH, enoxaparin mg single dose , with apixaban 5-mg single dose , an additive effect on anti-FXa activity was observed [ 64 ].
Exposure—Response Analyses with Bleeding or Efficacy Endpoints In VTE prevention in orthopedic surgery subjects, a Cox proportional hazards model showed a statistically significant relationship between individual daily AUC at steady state and any bleeding endpoint [ 40 ]; a two-fold increase in apixaban daily AUC is expected to increase bleeding frequencies from 6.
Antidote The administration of activated charcoal may be useful in the management of apixaban overdose or accidental ingestion. Conclusions Apixaban, a direct FXa inhibitor, has predictable PK and PD properties that are consistent across the range of different patient populations studied, including the elderly and those with renal impairment.
Acknowledgements The authors thank Yan Song for her contributions to the development of this manuscript. Conflict of interest Wonkyung Byon and Rebecca A. Consent to participate Informed consent was obtained from all individual participants included in the studies. References 1. Bristol-Myers Squibb. Coumadin wafarin sodium prescribing information. Accessed 2 Feb EU summary of product characteristics: Eliquis apixaban tablets.
Accessed 8 Apr Eliquis apixaban prescribing information. Accessed 14 Jun Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. Apixaban in patients with atrial fibrillation. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. Apixaban or enoxaparin for thromboprophylaxis after knee replacement.
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