What is Eliquis?
Eliquis (generic: apixaban) is a blood-thinner medication that stops blood from clotting and reduces the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (a-fib). The drug works by blocking Factor Xa, which is a blood-clotting factor critical to the blood-clotting process. Eliquis was developed in a joint partnership between Pfizer and Bristol-Myers Squibb, and was approved by the U.S. Food & Drug Administration (FDA) in December 2012.
What’s the Problem?
Eliquis has recently been linked to reports of uncontrollable bleeding events including bleeding in the brain (cerebral hemorrhage), intestinal bleeding (GI bleed), kidney bleeding and deep vein thrombosis (DVT). Additionally, clinical trials used to approve Eliquis have been heavily criticized for containing inaccurate and missing data, reports of patients receiving incorrect doses of medication, and omitting adverse events including death.
Eliquis Clinical Trial Problems
Lawsuits allege that clinical trials used to support Eliquis’ approval were deeply flawed, which led patients to use a harmful drug that should not have been on the market in the first place. FDA delayed approval of Eliquis for 9 months over misconduct, errors, and an alleged cover-up at a clinical trial site in China. The agency said that the mistakes demonstrated a “pattern of inadequate trial conduct and oversight.”
The trial in question is known as ARISTOTLE (Apixaban for Reduction in Stroke and Other Thrombotic Events in Atrial Fibrillation). According to the FDA, problems with ARISTOTLE included:
- Failure to report adverse events (including deaths)
- Late reports of adverse events
- Exclusion of medical outcomes
- Reports of patients who were given the wrong medication or the wrong dosage.
The study was eventually published in the New England Journal of Medicine (NEJM), but its findings were criticized by many, including former NEJM editor-in-chief Arnold Relman, who pointed out flaws in the study and said that financial interests influenced its conclusions.
According to Relman, ARISTOTLE failed to demonstrate that Eliquis is more effective than warfarin, while data may have been skewed to make Eliquis appear safer than it actually is. He cited the study as a prime example of how cozy ties between the pharmaceutical industry and researchers can result in fraudulent test results. At least three of the study’s authors were Bristol-Myers Squibb employees, according to Relman.
As to why Pfizer and Bristol-Myers were so eager to introduce a new blood-thinner that is little if any better than warfarin, it helps to follow the money. The annual cost of Eliquis is over 10 times higher than the annual cost of warfarin.
Eliquis Side Effects
Serious side effects of Eliquis include:
- Uncontrolled bleeding
- Gastrointestinal (GI) bleeding
- Hemorrhagic stroke (brain bleed)
- Intracranial hemorrhage (bleeding in the skull)
- Kidney bleeding
- Rectal bleeding
- Blood clot
- Deep vein thrombosis
- And more
No Antidote to Stop Bleeding
There is little evidence to support the manufacturers’ claims that Eliquis is safer and more effective than warfarin, a staple blood-thinner drug that’s been in use for over 50 years in the U.S. And unlike warfarin, Eliquis does not have an antidote that allows doctors to reverse bleeding complications, nor does it require regular blood monitoring that can help prevent dangerous bleeding events.
Eliquis Black Box Warning
In August 2014, FDA required the labeling of Eliquis to carry a “black box” warning (PDF) regarding the stroke risk associated with the medication:
WARNING: DISCONTINUING ELIQUIS IN PATIENTS WITHOUT ADEQUATE CONTINUOUS ANTICOAGULATION INCREASES RISK OF STROKE
“Discontinuing ELIQUIS places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation of ELIQUIS in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with ELIQUIS must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered.”
Eliquis vs. Warfarin
Data from ARISTOTLE found that Eliquis was superior in efficacy and bleeding profile compared to warfarin. Among a-fib patients, Eliquis bested warfarin in preventing strokes while also reducing the risk of bleeding by 31%. Additionally, Eliquis cut the risk of death from any cause by 11%, making it the first new anticoagulant to significantly improve mortality.
Eliquis was shown to prevent strokes about as good as Pradaxa (dabigatran) and slightly better than Xarelto (rivaroxaban). Pradaxa demonstrated superior efficacy but not safety vs. warfarin, and Xarelto was non-inferior to warfarin on efficacy and safety.
Lawsuits are now being filed alleging that Eliquis causes significant bleeding, deep vein thrombosis, and other serious side effects. Plaintiffs contend that Pfizer and Bristol-Myers Squibb failed to adequately warn the public and medical community that there is no antidote to reverse the blood-thinning effects of Eliquis. Complaints have also been filed on behalf of individuals who died due to complications from uncontrollable bleeding events, allegedly as a result of using Eliquis.
March 2010 – Clinical trial published
March 2010 – ARISTOTLE clinical trial published in the American Heart Journal.
December 2012 – Approved by the FDA
December 28, 2012 – Eliquis first approved by the FDA.
July 2013 – Accepted for review
July 11, 2013 – FDA accepts Eliquis Supplemental New Drug Application for review for prophylaxis of deep vein thrombosis following hip or knee replacement surgery.
March 2014 – Approved to reduce risk of blood clots
March 18, 2014 – FDA approves Eliquis to reduce the risk of blood clots following hip or knee replacement surgery,
August 2014 – FDA requires warning
August 2014 – FDA requires “black box” warning on Eliquis regarding increased stroke risk.
July 2015 – Lawsuit filed
July 24, 2015 – First Eliquis lawsuit filed.
- “ELIQUIS® (apixaban) tablets: RISK EVALUATION AND MITIGATION STRATEGY (REMS)”. Bristol-Myers Squibb Company. August 2014.
- “Chinese Trial Misconduct Delayed Bristol-Myers Medicine”. Bloomberg. July 8, 2013.
- “Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale”. American Heart Journal. March 2010.