Cost prevents heart patients from receiving adequate care

Dan Devine

When the Food and Drug Administration announced last June that it had approved a drug that reduced death and hospitalization in black heart failure patients by roughly 40 percent, it looked like help was on the horizon for hundreds of thousands of afflicted souls.

But thirteen months later, a collision between the medicine’s cost and a cautious health care bureaucracy has left many black patients waiting for the cavalry to arrive.

In the middle are cardiologists like Dr. Flora Sam, director of clinical research for the heart failure program at Boston Medical center, who must balance the health needs of her patients with the ability to pay.

Dr. Sam believes cardiologists not prescribing BiDil have some explaining to do.

“For my colleagues who aren’t putting patients on [BiDil] who are African American and have heart failure, I think they need to readdress it,” Dr. Sam said. “In cardiology, we always pat ourselves on the back for saying that we follow the guidelines of evidence-based medicine.

“[Not prescribing] this medication,” Dr. Sam added, “I would go so far as to say it’s malpractice.”

Her extremely tough words describe an equally difficult problem.

Heart failure weakens the heart’s ability to pump, leaving it unable to circulate enough blood to meet the body’s needs. Roughly 50 percent of heart failure patients die within five years of diagnosis, a survival rate worse than many cancers. There is no cure.

Of the nearly five million Americans diagnosed with heart failure, an estimated 750,000 are African American, a number expected to increase to nearly 900,000 by 2010. Statistics show that the impact of heart failure on blacks is simply devastating.

According to the National Heart, Lung and Blood Institute, blacks tend to develop heart failure younger than whites, leading to earlier disability and higher rates of both hospitalization and premature death. The Centers for Disease Control and Prevention estimate that blacks between the ages of 45 and 64 are 2.5 times more likely to die from heart failure than non-African Americans in the same age range.

A drug called BiDil could change that. The pill, marketed by Lexington-based pharmaceutical company NitroMed, Inc., combines fixed doses of hydralazine hydrochloride and isosorbide dinitrate, two medications that make it easier for the heart to pump by relaxing blood vessels and increasing blood flow.

Two trials conducted in the 1980s tested the combination’s impact on reducing mortality in heart failure patients, showing no significant decrease in the general populations studied. But subsequent analysis showed that it improved the survival of black patients. In 2000, NitroMed presented the reanalyzed data to the FDA, proposing the combination as a treatment for heart failure in blacks.

After the FDA said that a clearly positive trial in African Americans could provide a basis for approving the drug, NitroMed joined with the Association of Black Cardiologists in June 2001 to conduct the African American Heart Failure Trial (A-HeFT), the first clinical trial featuring all black participants.

All patients received what NitroMed chief medical officer Dr. Michael Sabolinski called “absolute best care for heart failure.” The trial featured two groups: one taking BiDil in addition to “best care,” the other receiving “best care” plus a placebo.

The results, Sabolinski said, were “truly remarkable.”

Patients in the BiDil group experienced a 43 percent decrease in the risk of mortality and a 39 percent reduction in the risk of first hospitalization for heart failure. The results were so staggering that the Independent Data and Safety Monitoring Board (DSMB) and Steering Committee unanimously recommended stopping the trial so that all participants could start taking BiDil.

“Fewer patients died, they stayed out of the hospital and they felt better, too,” Sabolinski said. “There are some medications that may improve survival, but you feel like hell [when you take them]. This is a drug where you feel much better after taking it.”

On June 23, 2005, based in part of the results of the A-HeFT study, the FDA approved BiDil.

“The information presented to the FDA clearly showed that blacks suffering from heart failure will now have an additional safe and effective option for treating their condition,” said FDA associate director of medical policy Dr. Robert Temple.

But making that option widely available to patients has proven difficult.

According to a July 12 story in the Springfield (Mo.) News-Leader, less than two percent of African Americans suffering from chronic heart failure currently take BiDil. The drug’s slow progress can be traced back to concerns in the health care community about its cost.

The cost question has dogged NitroMed since July 2005 when the company, citing market research on BiDil’s perceived value, set its price at $1.80 per pill, significantly higher than initial projections. Because BiDil is intended to be taken three times a day, with some patients recommended to take two pills per dose, the medication could cost between $5.40 and $10.80 per day.

The announcement drew disappointment from critics who felt NitroMed was pricing BiDil beyond the means of the patients it was intended to help.

Dr. James E. Hartert, chief medical officer for prescription drug insurance program Prime Therapeutics, told reporters at the time of the announcement that “those individual components, if purchased generically, cost under 25 cents a tablet.”

William “B.J.” Jones, NitroMed’s vice president of marketing, called the retail price point a “misnomer” that does not account for discounts throughout the health care community.

“No one pays that [price], certainly not the patients,” Jones said. “Neither do the insurers, because there’s a discount structure in place. The real price that’s meaningful is the price a patient has to pay at pharmacy.”

That “meaningful” price depends on two factors: whether a patient’s health plan covers BiDil, and how the plan classifies the medication in its co-pay structure.

Health care providers who foot the bill for their members’ pharmacy benefits don’t want to pay more for brand-name drugs when generic medications are available that can approximate their effects at a fraction of the cost.

NitroMed has faced an uphill battle to get BiDil included on a number of major plans because the two medications it combines are generics that cost providers far less on their own. And if insurance doesn’t cover the drug, the out-of-pocket cost for patients can be astronomical, sometimes as high as $100.

So the argument for providers, physicians and patients goes: Why pay more for a pill that combines two things you can put together on your own for less?

“I have prescribed the individual components separately, but not actually BiDil itself, because it’s my understanding that it’s quite an expensive medicine,” said Dr. James Chang, a cardiologist at Beth Deaconess Israel Medical Center. “Individually, these components are quite cheap, and many of my patients have financial considerations.”

Dr. Steven Nissen, who led the FDA advisory panel that recommended approving BiDil, said despite the combination’s convenience, “it’s just not worth spending an extra $100 a month to avoid taking a few extra pills.”

Sam, who led a clinical trial of BiDil at Boston Medical Center, prefers BiDil because of the convenience it provides for the patient. But when cost is an issue, she prescribes the generics.

“The only time I ever use a generic is if people are paying out of pocket and the cost is simply too high for them to buy the name-brand drug,” Sam said. “[But] if you’re not putting [patients] on hydralazine or nitrates, you are not following the guidelines of best care. I don’t care whether you prescribe the generics or the name brand, but this is what has been proven to work.”

Sabolinski bristled at the notion that there is no difference between BiDil and the individual generics.

“If anyone thinks you can mimic the effects of BiDil by doing anything other than using BiDil, I think you’re playing with fire,” he said. “There is just too much room for error … this seems to be a no-brainer to me — this is heart failure. [If you get it wrong,] you die.”

NitroMed’s stance gained support in May, when the FDA issued a letter confirming that it had not approved any drug “therapeutically equivalent or substitutable to BiDil,” including the individual components.

But even after the FDA letter, providers have been slow to cover BiDil. According to the News-Leader’s report, only a quarter of the nation’s insurance plans currently cover BiDil, and Jones acknowledged significant difficulty in gaining broad access on Medicare plans, specifically the Part D programs introduced earlier this year.

BiDil does not appear on the preferred drug lists of Blue Cross-Blue Shield of Massachusetts, Tufts Health Plan or Neighborhood Health Plan — three of the Commonwealth’s major commercial providers.

While Aetna doesn’t include BiDil on the preferred drug list for its commercial plans, it does cover the medication on its Medicare Rx plan; however, physicians must obtain permission from Aetna before their patients can fill BiDil prescriptions. This requirement, called precertification or prior authorization, enables providers to cut costs by using less expensive alternatives and preventing unnecessary or redundant treatments.

Of the 49 states whose Medicaid assistance covered BiDil, thirteen — including Massachusetts’ MassHealth program — required prior authorization for the prescription to be filled.

Jones says such cost-cutting measures often make it harder for patients to get treatments doctors deem necessary.

“In general, if a patient receives a prescription for BiDil from a clinician and goes to the pharmacy, the pharmacist will not fill that prescription. The pharmacist has to call back and get an authorization from the physician, who needs to go to [the insurer] and say, ‘My patient needs this medicine,’ and there’s usually someone saying, ‘You need to try X, Y, or Z medications first,’” Jones said. “There are hurdles that doctors and patients have to go through to get product, as opposed to just being able to go to the pharmacy and pick it up. You could call it access, but it’s not really functional access.”

The fight for access doesn’t end with plan inclusion. Health plans classify covered medications in a three-tier system based on their cost to the insurer and their co-pay for the patient. Tier 1 is usually reserved for generic drugs and Tier 2 includes low-to-medium cost brand name drugs, while Tier 3 consists of higher-priced brand name drugs.

Many plans, including Harvard Pilgrim Health Care, place BiDil in Tier 3, which often features average co-pays of $40-$50 or higher. Jones calls that price “extremely burdensome,” specifically for many in the African American population BiDil targets.

“We’ve been working diligently … with payors and plans so that they would be able to provide what we believe is an accessible co-pay for their patients,” Jones said. “The Tier 2 co-pays are usually in the neighborhood of $20-30, and we’ve gotten feedback from clinicians as well as patients that if the drug is in that space, then that’s something accessible.”

Through its “NitroMed Cares” patient assistance program, the company has also established two support plans to make BiDil less expensive for patients.

The Uninsured Patient Program offers free pills to patients ineligible for state or federal insurance who also lack private prescription drug coverage, while the Co-Pay Savings Card Program discounts co-pays for commercial patients, ensuring that they will not have to pay more than $25 for their medication. Patients must complete an application, which is then sent by their physicians to NitroMed’s program administrator, to enroll for either program.

But all the paperwork makes critics like heart failure specialist Dr. Jonathan Sackner-Bernstein of North Shore University Hospital in New York worry that not all eligible patients will actually receive assistance.

“I’m skeptical about these plans,” Sackner-Bernstein told reporters. “Since they require doctors to send in forms, they don’t work as well as they are supposed to.”

Exact numbers of patients enrolled for the Co-Pay Savings Card Program were unavailable due to its recent July 1 relaunch, but Jones said that roughly 400 patients have presently signed up to receive free BiDil through the Uninsured Patient Program.

Jones calls the programs necessary in the absence of industry-wide support.

“Because the plans have not moved rapidly enough, we’re doing what we can to provide that access in a much faster manner until we can actually get the plans up and on board in providing broad access to our patients,” Jones said.

After a year of false starts, that access may be on its way. According to Sondra Newman, NitroMed’s director of investor relations, the company has recently reached agreements with UnitedHealthcare, Highmark and Medco, the nation’s second largest pharmacy benefit manager, to ensure Tier 2 placement. Jones identified pharmacy managers like Caremark, Express Scripts and Prescription Solutions as targets for future partnerships.

In addition to its continued lobbying efforts and direct-to-consumer marketing strategy of spreading information about BiDil at African American health summits and church fairs, NitroMed is developing an extended release formulation that would enable patients to take one pill per day instead of three, which Sabolinski believes will make it easier for patients to comply with their treatment.

“You constantly want to improve on what you have,” Sabolinski said. “It’s too important a disease to not try to improve on our product.”