While Eliquis advertisements tout the benefits of the drug, they fail to mention the risk of serious, uncontrollable bleeding.
The blood thinner Eliquis (apixaban) has been linked to serious, potentially fatal bleeding that that cannot be reversed with an antidote.
Eliquis was introduced in 2012 as a superior alternative to the anticoagulant warfarin. Some experts, however, dispute whether Eliquis is in fact safer or more effective than warfarin. There is also controversy surrounding the validity of clinical data used to approve Eliquis.
On the back of an aggressive marketing campaign, Eliquis sales have exploded and the drug has earned its makers billions of dollars. But while Eliquis advertisements tout the “benefits” of the drug, they fail to mention the lack of a bleeding reversal agent and the significance of this problem for patients who experience serious, uncontrollable bleeding.
Patients harmed by Eliquis have filed lawsuits against drug makers Bristol-Myers Squibb and Pfizer, seeking financial compensation for bleeding complications.
Eliquis hit the U.S. market in 2012. It is the latest member of a new generation of blood thinners (anticoagulants) designed to replace warfarin, which has been on the market since the 1950s.
In 2016, Eliquis generated $3.34 billion in sales.
Eliquis may be prescribed for the following uses:
- Lower the risk of stroke and blood clots in patients with atrial fibrillation (AFib)
- Treat and prevent blood clots in the legs (deep vein thrombosis) and lungs (pulmonary embolism)
- Reduce the risk of blood clot formation in the legs and lungs of patients who have undergone hip or knee replacement surgery
In 2016, Eliquis generated $3.34 billion in sales.
How Eliquis Works
Eliquis belongs to a class of drugs known as “Factor Xa inhibitors.”
Factor Xa is an enzyme that plays a key role in blood clotting. Eliquis contains the active ingredient apixaban, which inhibits (or blocks) Factor Xa. By blocking Factor Xa, Eliquis reduces the chance of a blood clot forming.
Other Factor Xa inhibitors include Lixiana and Xarelto.
Eliquis Bleeding Risks
Hemorrhage is an inherent risk of all anticoagulant drugs because the drugs reduce blood clotting. Blood clots are for the most part desirable, such as when the body is injured and bleeding needs to be stopped. But since they prevent clotting, anticoagulants can also cause bleeding. These bleeding events can be fatal.
Eliquis patients have reported hemorrhages in body regions that include:
- Gastrointestinal tract
Eliquis Adverse Event Reports
The Institute for Safe Medicine Practices (ISMP) tracks adverse event reports associated with U.S.-sold pharmaceuticals. In 2014, ISMP recorded the following Eliquis adverse events:
- 1,014 total Eliquis adverse events
- 108 fatal events
- 492 hemorrhage cases
- 224 embolic-thrombotic cases (lodging of a blood clot in an artery)
Eliquis vs. Warfarin
Warfarin, approved in 1954, was for decades the industry-standard blood thinner. Although not a perfect drug (again, all anticoagulants present a risk of hemorrhage complications), warfarin is a tried and true therapy for patients at risk for serious, disabling blood-clot-related events such as stroke.
Generic blood thinners cost less than $20/month, compared to $300/month or more for Eliquis.
The problem with drugs like warfarin that have been on the market for many years (at least from a drug maker’s perspective) is that they lose patent protection and can be sold cheaply as generics. Through the patenting of new drugs, manufacturers obtain the exclusive right to sell drugs without generic competition, thereby increasing profit margins. Case in point: generic warfarin costs less than $20/month, compared to $300/month or more for the new anticoagulants Eliquis, Xarelto, and Pradaxa.
Rather than tackling the much more difficult tasks of creating new anticoagulants that are superior to warfarin in terms of effectiveness and safety, drug makers focused on designing new anticoagulants that are easier to use than warfarin. As ISMP explains, the companies that make Eliquis, Xarelto, and Pradaxa “opted for ease of use over improved safety.”
This is why the makers of Eliquis boast that the drug (unlike warfarin) requires no routine blood testing, no dietary restrictions, and no regular dose adjustments. In addition, BMS and Pfizer claim, clinical trials proved that Eliquis reduces the risk of stroke better than warfarin and produces less major bleeding than warfarin.
But the clinical trials on which these claims are based have come under scrutiny for alleged major shortcomings.
Problems With Eliquis Clinical Data
The Food and Drug Administration (FDA) delayed approving Eliquis for 9 months over conduct issues with clinical trial sites in China (drug companies are turning to Chinese clinical trials because they are cheaper to run).
According to FDA, problems with the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thrombotic Events in Atrial Fibrillation) trial, which compared Eliquis to warfarin, included:
- A high percentage of patients received the wrong drug or the wrong drug dose.
- Adverse medical events, including death, were not reported.
- Source records were altered to cover up evidence of clinical practice violations.
- Certain medical outcomes were excluded from study data, in favor of Eliquis.
FDA decided that these irregularities did not significantly impact clinical trial results, but when the data—which purports to show that Eliquis is superior to warfarin in preventing stroke and deaths—was published in the New England Journal of Medicine (NEJM), former NEJM editor Dr. Arnold Relman said that the study was too flawed for publication.
Dr. Relman points out that the ARISTOTLE study had key limitations that were not mentioned in the study’s discussion, including:
- Eliquis was not shown to be more effective than warfarin.
- 35 percent of warfarin patients were given non-therapeutic doses of the drug, which may have contributed to these patients experiencing a higher rate of blood clots and strokes compared to the Eliquis group.
Relman blames these limitations on financial ties to the drug industry. Bristol-Myers Squibb and Pfizer funded ARISTOTLE, and the study fine print reveals that three of the study authors were BMS employees.
Not surprisingly, research shows a link between a drug company funding clinical research and favorable trial outcomes for that company’s drug.
Lack of Eliquis Bleeding Reversal Agent
Describing Eliquis as “safer” than warfarin is dubious not only due to questionable safety data, but also due to the fact that Eliquis does not have an antidote that can stop internal bleeding, which left untreated can be fatal.
Bristol-Myers Squibb and Pfizer are quick to point out the benefits of Eliquis compared to warfarin on the product website and in advertisements, but they are less forthcoming about how the lack of a bleeding antidote can lead to life-threatening consequences.
Eliquis has no boxed warning that describes its lack of a bleeding antidote.
Hemorrhagic complications associated with warfarin can be controlled with the administration of vitamin K and other substances. But when an Eliquis patient develops dangerous bleeding, the blood thinning effects of the drug cannot be stopped, making it more likely that complications will be catastrophic.
Eliquis has no “boxed warning” that describes its lack of a bleeding antidote. It is only mentioned in the fine print of Eliquis’ prescribing information insert. Promotional materials provided to physicians from sales drug company sales reps also do not make it clear that Eliquis lacks a bleeding reversal agent.
Eliquis Aggressively Marketed to Patients, Doctors
Following FDA approval of Eliquis, BMS/Pfizer engaged in an aggressive, multi-million dollar advertising campaign for the drug. In addition to extensive marketing directed to the public via TV and print, BMS/Pfizer have made more than $45.9 million in physician payments to nearly 96,084 doctors, according to ProPublica.
Drugmakers claim that spending on physicians helps ensure that doctors understand how to properly use their drugs, while doctors have long claimed that payments from pharmaceutical companies do not influence their prescribing patterns. But common sense—and research—say that the more drug companies pay physicians, the more those physicians prescribe their drugs.
As part of its Dollars for Doctors project, non-profit ProPublica performed an analysis that confirmed this trend. “The more money [doctors] receive, on average, the more brand-name medications they prescribe,” concludes ProPublica.