PRINCETON, N.J. & NEW YORK--(BUSINESS WIRE)--The Bristol Myers Squibb-Pfizer (BMS NYSE: BMY) – (Pfizer NYSE: PFE) Alliance today presented results from ATHENS, a retrospective real-world data study, at the European Society of Cardiology (ESC) Congress 2023 showing that switching from Eliquis® (apixaban) to rivaroxaban in Non-Valvular Atrial Fibrillation (NVAF) patients was associated with a higher risk of stroke/systemic embolism (S/SE) and major bleeding (MB) than those who continued Eliquis.
“Although some NVAF patients switch direct oral anticoagulants in real-world clinical practice, either for medical or non-medical reasons, there hasn’t been a lot of information gathered on the clinical outcomes of those switches,” said Steve Deitelzweig, MD, MMM, FACC, SFHM, FACP, RVT, System Chairman for Hospital Medicine, Ochsner Health System. “The study results provide insights about the real-world risk of stroke and major bleeding associated with switching from apixaban to rivaroxaban in patients with NVAF.”
This retrospective study identified NVAF patients who initiated Eliquis or rivaroxaban between 01 January 2013 and 31 December 2021 using Optum’s de-identified Clinformatics® Data Mart database. There were 167,868 Eliquis initiators and 65,888 rivaroxaban initiators who met study criteria. Using propensity score matching (PSM), 2,900 patients who switched from Eliquis to rivaroxaban were matched to 14,500 patients who continued Eliquis, and 2,873 patients who switched from rivaroxaban to Eliquis were matched to 14,365 patients who continued rivaroxaban.
"Data collected in real-world settings can enhance patient care. By gathering insights from everyday clinical practice, we can better understand how Eliquis is used and its impact on patients’ lives,” said Narinder Bhalla, MD, Senior Vice President, Worldwide Medical, Head of Cardiovascular and Established Brands at Bristol Myers Squibb. “This real-world data provides pragmatic information to help clinicians manage the care of their patients.”
In this study, switching from Eliquis to rivaroxaban was associated with a higher risk of S/SE (Hazard Ratio (HR):1.99, 95% Confidence Interval (CI): 1.38-2.88) and MB (HR: 1.80, 95% CI: 1.46-2.23) than those who continued Eliquis. Additionally, switching from rivaroxaban to Eliquis was associated with a similar risk of S/SE (HR:0.74, 95% CI: 0.45-1.22) and a lower risk of MB (HR:0.58, 95%CI: 0.44-0.76) compared to those who continued rivaroxaban. It is important to note that anticoagulants, including Eliquis, increase the risk of bleeding and can cause serious, potentially fatal bleeding. Please see important safety information below for Eliquis, including BOXED WARNINGS.
Real-world data have the potential to supplement randomized, controlled clinical trial data by providing additional information about how a medicine performs in routine medical practice. Real-world data analyses, however, have important limitations. Observational real-world studies can only evaluate association and not causality, and despite the use of methods to address differences due to measured variables, false associations may still be present. The source and type of data used may limit the generalizability of the results, and varied outcomes are possible.
In the ATHENS study, treatment assignments were based on pharmacy claims and actual drug exposure is unknown. Additionally, reasons for switching are not known and sample size for those who switched is much lower than those who continued treatment. Dosing criteria were not evaluated and impacts of drug dosing on outcomes were not assessed. Due to these limitations, real-world data analyses are not used as evidence to validate the efficacy and/or safety of a treatment.
About ATHENS
The ATHENS study was designed to assess the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among Non-Valvular Atrial Fibrillation (NVAF) patients who switched from Eliquis (apixaban) to rivaroxaban or switched from rivaroxaban to Eliquis instead of continuing initial treatment. This retrospective study identified NVAF patients who initiated treatment between 01 January 2013 and 31 December 2021 using a large U.S. administrative claims database. There were 167,868 Eliquis initiators and 65,888 rivaroxaban initiators included in the study.
Within both the Eliquis initiators and rivaroxaban initiators cohorts, patients were divided into two groups and compared: switchers to a different direct oral anticoagulant (DOAC) within 30 days before or 90 days after discontinuation of the initial DOAC, and continuers, or patients who continued receiving the initial DOAC. The switch date was the index date for those who switched while, for those who continued, a hypothetic index date was randomly assigned based on the distribution of the time from initial DOAC prescription to the switch date in the switchers group. Two final cohorts (switchers and continuers) within Eliquis initiators and rivaroxaban initiators were further propensity score matched (PSM) based on pre-index characteristics using a 1:5 ratio.
About Eliquis® (apixaban)
Eliquis® is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, Eliquis decreases thrombin generation and blood clot formation. Eliquis is approved for multiple indications in the U.S. based on efficacy and safety data from multiple Phase 3 clinical trials. The approval of Eliquis for stroke risk reduction in patients with NVAF is based on data from the Phase 3 ARISTOTLE and AVERROES studies of Eliquis in patients with NVAF. The approval of Eliquis for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for the reduction in the risk of recurrent DVT and PE following initial therapy, is based on data from the global AMPLIFY and AMPLIFY-EXT studies. U.S. FDA-Approved Indications for Eliquis: Eliquis is a prescription medicine indicated in the U.S. to reduce the risk of stroke and systemic embolism in patients with NVAF; 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; for the treatment of DVT and PE; and to reduce the risk of recurrent DVT and PE, following initial therapy.
Eliquis Important Safety Information
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.
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 PRECAUTION
- 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.
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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.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
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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.
Please see U.S. FULL PRESCRIBING INFORMATION, including Boxed WARNINGS, available at www.bms.com.
About the Bristol Myers Squibb-Pfizer Collaboration
The Bristol Myers Squibb-Pfizer Alliance (the Alliance) is committed to driving education and awareness about atrial fibrillation and deep vein thrombosis (DVT) and/or pulmonary embolism (PE). With long- standing cardiovascular leadership, global scale and expertise in this field, the Alliance strives to implement global, research-driven approaches to illuminate and address the unmet needs around strokes related to non-valvular atrial fibrillation, which are often fatal or debilitating. Through collaborations with non-profit organizations, the Alliance aims to provide patients, healthcare professionals and decision makers with the information they need to understand and take appropriate action on risk factors associated with stroke and other cardiovascular conditions.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
About Pfizer Inc.: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines.
Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
Bristol Myers Squibb Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2022, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
Pfizer Disclosure Notice
The information contained in this release is as of August 25, 2023. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about Eliquis (apixaban), including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical or other data and further analyses of existing clinical or other data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of Eliquis; uncertainties regarding commercial success; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results,” as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
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