"I've never seen an issue galvanize the cardiovascular community like this," said Ryan Gough, executive director of the Partnership to Advance Cardiovascular Health.
For eight years, Beth Joyner Waldron has counted on Eliquis to treat clots in her lungs and legs.
In November 2021, she received a letter from CVS Caremark telling her the pharmacy benefit manager is excluding Eliquis from its formulary next year. Receiving the letter made her emotional.
Just a year ago, her father bled to death. Joyner Waldron said he had an adverse reaction to his blood thinner. "I nearly died from my blood clots 18 years ago and I know from my dad's experience the treatment carries a high risk," Joyner Waldron said. "I've been stable, I've not had any bleeds, and then I get this letter saying I have to switch meds, that obviously induces anxiety." She also was angry that the letter did not include information on how to appeal the decision. As of January 1, one of the nation's largest pharmacy benefit managers no longer covers a blood thinner that Joyner Waldron and an estimated 3 million others rely on to prevent and treat blood clots. Just five weeks before the formulary change was made, CVS' $39 billion Caremark subsidiary sent letters to its commercial enrollees, alerting them that they would need to switch from Bristol-Myers Squibb's Eliquis to Janssen Pharmaceuticals' Xarelto, both anticoagulants that experts say have never been proved to be interchangeable through randomized control trials. The formulary exclusion comes as PBMs increasingly drop medications from their coverage lists, attracting attention from federal and state lawmakers aiming to reign in non-medical switching, said Ryan Gough, executive director of the Partnership to Advance Cardiovascular Health, a patient advocacy group.
"I've never seen an issue galvanize the cardiovascular community like this," Gough said. The decision sparked outcry from 14 patient advocacy groups, which wrote to CVS Health's chief medical officer in December calling for him to reverse the "dangerously disruptive" decision. Experts from the American College of Cardiology and American Society of Hematology also continue to meet with CVS Caremark about the move.
The company is committed to providing safe, effective and clinically appropriate medication for its PBM and Aetna health insurance customers, a spokesperson wrote in an email. CVS did not respond to requests over how many people this formulary change would impact, and how much money the change would save the PBM or its customers.
"We closely monitor medical literature for all formulary decisions, and changes are evaluated by external medical specialists and an independent national pharmacy and therapeutics committee," the spokesperson wrote. "When evidence-based formulary changes such as this one are made, we communicate proactively with members who may be impacted and provide continuing coverage of medications when clinically appropriate."
One of these things is not like the other
There are no randomized clinical trials that show Eliquis and Xarelto can be used interchangeably. But observational studies have shown the two anticoagulants are not the same.
A December 2021 study published in the Annals of Internal Medicine, for example, reviewed the insurance claims for nearly 50,000 patients and found new users of Eliquis had lower rates of recurrent blood clots and bleeding, compared with new users of Xarelto, for example. Other studies have concluded that Eliquis presents less risk for gastrointestinal bleeding than Xarelto and that patients were more likely to properly adhere to their prescription.
CVS Caremark executives should look to these studies when making decisions about formulary exclusions, particularly when clinical trials directly comparing the two drugs do not exist, said Dr. Geoffrey Barnes, a cardiologist and associate professor at the University of Michigan. Barnes serves as a consultant to both Janssen and Bristol-Myers Squibb about their blood thinners. "We're worried that there are patients who are less able to navigate what is an increasingly complex healthcare and insurance landscape, where now they have to figure out how to switch medicines," Barnes said.
He said he was concerned about switching drugs for patients with kidney disease or cancer, since observational studies have shown that these individuals have a higher risk of bleeding while using Xarelto. Additionally, he noted that women who use Xarelto commonly experience heavier menstrual bleeds, which can be life-threatening. Barnes raised these concerns with CVS Caremark executives in December.
CVS did not respond to questions about whether the drugs were interchangeable.
"There are going to be physician offices that have more resources and dedicated staff to advocate on behalf of patients and other offices that don't have those resources," Barnes said. "We are very concerned that all of those together will worsen disparities for patients." At that meeting, CVS officials said the switch was made, in part, because Xarelto has been approved as a treatment for more conditions than Eliquis, said Dr. Jean Connors, director of the anticoagulation management service at Brigham and Women's Hospital and the Dana-Farber Cancer Institute and a professor at Harvard Medical School. The PBM also assumed that commercial patients were younger, healthier and less likely to experience side effects from the switch, she said.
After CVS alerted customers about the formulary change, Connors said her office received a flood of calls from patients, anxious about the move and asking for help overturning the decision. One patient of hers – who happens to work in the corporate office of CVS Health – was switched to Xarelto and experienced heavier periods, she said. Another did not contact her office about a prescription refill until they had just three days worth of medication left, and waiting for CVS to approve the medication interrupted their treatment.
"It's kind of like changing the course of the Titanic, right?" Connors said. "Whose suffering here? The patient with anxiety about whether or not they can get a drug they've been on for a while, or the doctor who thinks this is the best drug for them? Is CVS dealing with this? No, it's the burnt out physicians and their staff."
Connors has another meeting scheduled with CVS Caremark in March. She doesn't expect the company to add Eliquis back to their formulary in 2022.
The company's move to drop Eliquis comes as the PBM increasingly pushes drugs from its formulary, excluding 433 products in 2022, up from 417 the year before, according to an analysis by the Drug Channels research consultancy. CVS has said that only 0.4% of its members will be affected by its 2022 exclusions. UnitedHealth Group's OptumRx and Cigna's Express Scripts both continue to include Eliquis in their 2022 formularies, albeit at different tiers. Across these PBMs–which control 75% of the market–formulary freezes have increased recently, with each excluding more than 400 products in 2022. Growing coverage restrictions have led more legislators to look at how they can crack down on non-medical switching, said Antonio Ciaccia, head of 46brooklyn Research drug pricing consultancy. At least three states passed legislation providing patient protections from the practice last year, bringing the total number of states with laws on the books to seven.
Similar legislation is currently pending in at least four other states. And the Partnership to Advance Cardiovascular Health said it was contacted by a Republican senator about introducing a bill to ban non-medical switching at the federal level; the patient advocacy group said the legislator is looking for a Democratic co-sponsor.
"One of the things that drives me nuts about this is that the drug prices are ridiculously overinflated because we have this twisted system," Ciaccia said. "It becomes almost unrealistic that a patient can obtain a product at this point without coverage."
While the list price for Eliquis increased 6% year-over-year, it is impossible to know how much CVS Caremark would pay for the drug because of the secret rebate deals inked with drug makers, Ciaccia said.
In Joyner Waldren's case, after spending tens of hours on the phone with CVS Caremark, the PBM did allow her prescription to go through–if she's willing to pay a $2,400 deductible. The cost for cash-pay customers is even higher, reaching more than $560 for a 60-day supply.
Joyner Waldron, a freelance writer and healthcare consultant, can't afford the medication in either case. She has enough Eliquis to last until the end of February. After that, she is tentatively planning on switching to Xarelto.
"We're captive consumers," Joyner Waldron said. "As a patient or consumer, I don't choose my PBM, I choose my insurance. I don't choose my PBM, yet they have pretty wide latitude to make clinical decisions that impact my care and override the decision of my doctor."