PRINCETON, N.J. & NEW YORK, N.Y.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) will present findings today from a real-world data (RWD) analysis titled, Comparison of Effectiveness, Safety, and the Net Clinical Outcome between Different Direct Oral Anticoagulants in 162,707 Non-Valvular Atrial Fibrillation Patients Treated in US Clinical Practice. This is the largest RWD analysis reporting outcomes among different direct oral anticoagulants (DOACs), including Eliquis® (apixaban), rivaroxaban and dabigatran, to date. In this analysis, apixaban use was associated with significantly lower rates of both stroke/systemic embolism (S/SE) (hazard ratio [HR]:0.83, 95% confidence interval [CI]: 0.73 to 0.94, p=0.004) and major bleeding (MB) (HR:0.54, 95% CI: 0.50 to 0.58, p=<0.001) when compared to rivaroxaban; and significantly lower rates of both S/SE (HR:0.69, 95% CI: 0.56 to 0.84, p=<0.001) and MB (HR:0.77, 95% CI: 0.68 to 0.88, p=<0.001) when compared to dabigatran.
This retrospective observational analysis utilizing pre-specified endpoints included three 1:1 propensity score individually matched DOAC cohorts: apixaban vs. rivaroxaban (n=125,238), apixaban vs. dabigatran (n=54,192), and dabigatran vs. rivaroxaban (n=55,076). The analysis also revealed that in the dabigatran vs. rivaroxaban cohort, dabigatran was associated with a significantly lower rate of MB (HR:0.67, 95% CI: 0.60 to 0.74, p=<0.001) and a non-significantly higher rate of S/SE (HR:1.18, 95% CI: 0.98 to 1.43, p=0.080). It is important to note that, at this time, there are no head-to-head clinical trials comparing DOACs. 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.
“Most observational, real-world data analyses of direct oral anticoagulants have used single data sources; in this analysis, we pooled CMS Medicare data and four U.S. Managed Care claims databases, including both commercial and Medicare Advantage lives, covering in total more than 180 million beneficiaries annually1,2 – more than half of the U.S. population,” said Steven Deitelzweig, M.D., System Department Chair of Hospital Medicine, Ochsner Medical Center, New Orleans, and one of the analysis’ primary investigators. “Being able to see patient claims from different data sets with good representation across the country may help decision making in clinical practice.”
Study Details: This was a retrospective observational cohort analysis of non-valvular atrial fibrillation (NVAF) patients utilizing pre-specified endpoints and analyzed using propensity-score matching (PSM). It includes NVAF patients (n=162,707) from ARISTOPHANES (Anticoagulants for Reduction In STroke: Observational Pooled analysis on Health outcomes ANd Experience of patientS), an ongoing real-world data analysis initiative that now includes anonymized patient records from more than 300,000 patients. The analysis presented at ACC includes patients who initiated apixaban, rivaroxaban or dabigatran, from Jan. 1, 2013, to Sept. 30, 2015, pooled from 5 large databases, including CMS fee-for-service Medicare data, Truven MarketScan® Commercial Claims and Encounter and Medicare Supplemental and Coordination of Benefits Database, the IMS PharMetrics Plus™ Database, the Optum Clinformatics™ Data Mart, and the Humana Research Database. After 1:1 DOAC-DOAC PSM in each database, the resulting patient records were pooled. Patients were followed for a mean of six months. Cox models were used to evaluate the rates of S/SE and of MB across DOACs within one year of therapy initiation. Patients with NVAF were included regardless of the dose of DOACs used.
Limitations of Real-World Data Analyses and of ARISTOPHANES: Real-world data have the potential to supplement randomized controlled trial data by providing additional information about how a medicine performs in routine medical practice. Real-world data analyses have several limitations. For example, the source and type of data used may limit the generalizability of the results and of the endpoints. Observational real-world studies can only evaluate association and not causality. Due to these limitations, real-world data analyses cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment. It is important to note that, at this time, there are no head-to-head clinical trials comparing direct oral anticoagulants.
In this analysis, although PSM was used to control for multiple confounders, there is still potential for residual bias. Claims for a filled prescription do not indicate that the medication was consumed or taken as prescribed. Also, medications filled over the counter or provided as samples are not captured in the claims data.
BMS-Pfizer Alliance Real-Word Data (RWD) Program: ARISTOPHANES is part of the Bristol-Myers Squibb-Pfizer Alliance global RWD analysis program, ACROPOLIS™ (Apixaban ExperienCe Through Real-WOrld POpuLatIon Studies), designed to generate additional evidence from routine clinical practice settings to further inform healthcare decision makers, including healthcare providers and payers. The ACROPOLIS program includes retrospective, outcomes-based analyses from over 16 databases around the world, including medical records, medical and pharmacy health insurance claims data, and national health data systems.
Analyses of real-world data allow for a broader understanding of patient outcomes associated with Eliquis outside of the clinical trial setting, as well as insight into other measures of healthcare delivery, such as hospitalization and costs.
Eliquis (apixaban) 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. Eliquis is a prescription medicine indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (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
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.
- 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.
- There is no established way to reverse the anticoagulant effect of apixaban, which can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is not available.
- 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.
- 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.
Combined P-gp and Strong CYP3A4 Inhibitors: Inhibitors of P-
glycoprotein (P-gp) and cytochrome P450 (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
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 CATEGORY B
- There are no adequate and well-controlled studies of ELIQUIS in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. ELIQUIS should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.
Please see full Prescribing Information, including BOXED WARNINGS and
Medication Guide, available at www.bms.com.
ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) was designed to evaluate the efficacy and safety of Eliquis versus warfarin for the prevention of stroke or systemic embolism. In ARISTOTLE, 18,201 patients were randomized (9,120 patients to Eliquis and 9,081 to warfarin). ARISTOTLE was an active-controlled, randomized, double-blind, multi-national trial in patients with nonvalvular atrial fibrillation or atrial flutter, and at least one additional risk factor for stroke. Patients were randomized to treatment with Eliquis 5 mg orally twice daily (or 2.5 mg twice daily in selected patients, representing 4.7 percent of all patients) or warfarin (target INR range 2.0-3.0), and followed for a median of 1.8 years.
About the Bristol-Myers Squibb/Pfizer Collaboration
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize apixaban, an oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb's long-standing strengths in cardiovascular drug development and commercialization with Pfizer’s global scale and expertise in this field.
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 and Facebook.
About Pfizer Inc.: Working together for a healthier world®
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. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. 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 150 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 @PfizerNews, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2017, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Pfizer Disclosure Notice
The information contained in this release is as of March 11, 2018. 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, without limitation, the ability to meet anticipated clinical trial commencement and completion dates as well as the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of Eliquis; 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, 2017 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.
1 Li, X et al. Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice. Thrombosis and Haemostasis. 2017; 6, 1,007-1,216. https://doi.org/10.1160/TH17-01-0068.
2 Amin, A 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. Current Medical Research and Opinion. DOI: 10.1080/03007995.2017.1345729