Vidyya Medical News Service
Volume 6 Issue 160 Published - 14:00 UTC 08:00 EST 8-Jun-2004 Next Update - 14:00 UTC 08:00 EST 9-Jun-2004
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Even among those who need them most, statin prescriptions go unfilled

Tens of millions of Americans take cholesterol-lowering drugs every day to keep their blood vessels clear and reduce their risk of heart attacks and other cardiovascular problems. Or do they?

A new study finds that nearly half of patients who have a prescription for any of the cholesterol-fighting drugs called statins fail to fill their prescription often enough -- or stop filling it altogether, even though statins give the most benefit if used long-term.

Not surprisingly, patients' out-of-pocket costs for these drugs are a contributing factor. Patients whose insurance plans make them pay more than $20 for each month's supply are three times more likely to fall behind on their prescription, and four times more likely to stop taking the drug altogether, than those whose co-pay is under $10, the new study finds.

In fact, researchers from the University of Michigan Health System and Cleveland Clinic report that almost half of those who were prescribed a statin didn't adhere to the treatment, and about half of first-time users discontinued taking the drug within four years. The team's paper, based on insurance and medical records for 4,802 patients, is in the June issue of the Journal of General Internal Medicine.

The low rate of adherence, and the impact of co-pays, was nearly equal for patients who just had high cholesterol and for those patients who needed statins even more, because they had already survived a heart attack, been diagnosed with diabetes or clogged blood vessels, or had surgery or angioplasty to open blocked arteries.

"This was a big surprise that the two groups were almost identical," says first author Jeffrey Ellis, Pharm.D., M.S., a Cleveland Clinic researcher who led the study while he was a fellow at the UMHS Department of Pharmacy Services. "We thought we'd definitely see less discontinuation and better compliance in the sicker patients because they've been through the realities of heart disease. But we didn't -- and the co-pay played a huge independent predicting role in non-adherence among all patients."

Ellis' co-author, UMHS Director of Pharmacy Services James Stevenson, Pharm.D., notes that the lack of adherence to cholesterol-lowering drugs might have something to do with the fact that there are no daily symptoms of having high cholesterol.

"Patients don't necessarily feel any different, so they don't get regular positive reinforcement for being on statins," he says. "But of course we know there's a direct preventive benefit from long term use. We should try to set up systems that encourage patients to stay on these drugs, and improve compliance."

The senior author on the paper, U-M professor of internal medicine A. Mark Fendrick, M.D., agrees. "Adherence appears to be lousy in both moderate and high-risk patients. To get the biggest 'bang for the buck' out of efforts to improve patient behavior, we first need to focus on improving adherence in those high-risk populations who are most likely to benefit," he says. He spurred the development of the new study in order to document the effect of co-pay level on adherence for patients with different levels of risk.

For several years, Fendrick has championed a concept he calls "benefit-based co-pay" that would charge patients different co-pay amounts based on how much they stand to benefit from taking a particular medication. Under the system, for example, a patient who has survived a heart attack and still has high cholesterol would pay less each time he or she refills a statin prescription than a person who has high blood cholesterol levels but no history of heart attack. Some patients might even pay nothing for a refill. Ellis adds, "There's solid evidence that statin use among heart attack survivors is more beneficial than for those with no heart history."

The new paper dovetails with a recently released study by the RAND Corporation that showed use of several groups of drugs, including anti-cholesterol medications, dropped when co-pays were raised. The RAND researchers, whose paper appeared in the May 19 issue of the Journal of the American Medical Association, found that people who had seen a doctor repeatedly about high cholesterol, and filled a prescription for the condition at least once, were less likely to stop filling their prescription when the co-pay rose than were patients who just had a prescription.

The new U-M/Cleveland Clinic study takes a more in-depth look at statin users. The researchers had full access to anonymous hospitalization, outpatient, prescription, and insurance claim records for 4,802 patients in managed-care insurance plans who had filled at least two prescriptions for a statin drug between January 1998 and November 2001.

Just under half (2,258) of the patients were "secondary prevention" patients whose records showed they had at least one reason in their health history to take a statin: a past heart attack, angioplasty or heart bypass surgery, or a diagnosis of chronic ischemic heart disease, coronary atherosclerosis, or type I or II diabetes, which was verified by pharmacy claims for insulin or antidiabetic drugs.

The researchers retrospectively analyzed the records for these patients, and for 2,544 "primary prevention" patients who had been prescribed statins for high cholesterol. Based on the prescription data and pharmacy claims, they calculated a quantity called a cumulative multiple-refill interval gap, or CMG, for each patient, to determine what percentage of days the patients were without enough pills to adhere to their treatment regimen.

Any patient who was without enough pills for one day out of 10, or 10 percent of the time, was considered to be non-adherent, and the researchers also looked at thresholds of 20 percent and 30 percent. Research suggests that patients who consistently miss more than one in every five doses of a statin have as much chance of heart attack and death as those not taking statins at all.

In addition to non-adherence, the researchers also looked for evidence of discontinuation -- patients who stopped filling or renewing prescriptions and who didn't switch to a non-statin drug, leave their insurance plan, or die. All other patients were presumed to need statins for the remainder of their lives, regardless of their risk level.

In all, the average CMG was about the same for both groups of patients, around 20 percent. The same percentage of patients in both groups -- 56 percent -- were classified non-adherent, with a CMG greater than 10 percent. Women, people under 65 years old, and African Americans were somewhat more likely to be non-adherent, as were those whose prescriptions called for them to take more than one dose a day, those who had changes in their dose or brand of statin during the study period, and those who got less than two months' supply of medication per refill.

But when the researchers broke down the patients according to their insurance plan co-pays, they saw a major difference: 76.2 percent of those whose out-of-pocket prescription cost was $20 or more for a month's worth of statin drugs were non-adherent, as opposed to 49.4 percent of patients whose monthly prescription co-pay was less than $10.

The same was true for those who discontinued use of statins for no apparent reason. The study looked at the 2,601 patients who received their first prescription for a statin during the study period. Within 3.7 years, half of the secondary prevention patients had discontinued use, and the same percentage of primary prevention patients had stopped within 3.4 years. The authors say this should concern physicians who treat heart and diabetes patients, as it is a faster rate of discontinuation than has been seen previously in patients who can benefit most from statins.

Patients whose monthly co-pay was $20 or over were four times as likely to discontinue as those who paid less than $10, and even those whose co-pay was between $10 and $20 were somewhat more likely to stop. Half of those who paid $20 or more a month stopped taking statins within a year of their first prescription, while those who had a lesser co-pay stayed on much longer.

Fendrick adds, "This impressive finding strongly supports a process that lowers or eliminates co-pays for those at highest risk for heart attacks. The value of statins and many other medical interventions should not be determined solely on the purchase price."

In all, the researchers say, the results should prompt insurance companies to look at designing co-pays that take into account how much an individual patient might benefit from taking a particular drug. And, the results should show clinicians how often their statin patients fall off their regimen.

"Doctors and pharmacists alike can tell patients all the benefits of a drug, and mention that they should stay on it and keep refilling their prescription, but as soon as a patient walks out the door it's up to him or her to fill the prescription or take the medication," says Ellis. "We need to be stronger in conveying that taking a statin regularly can be a matter of life or death, and we need to make it easier for patients who really need these drugs to get them and stay on them."

In addition to Ellis, Stevenson and Fendrick, the study's authors include Steven R. Erickson, Pharm.D., Steven J. Bernstein, M.D., and Renee Stiles, Ph.D., who is now at Vanderbilt University. Stevenson and Erickson hold joint appointments in the U-M College of Pharmacy, and Fendrick has a joint appointment in the U-M School of Public Health. Bernstein has a joint appointment at the VA Ann Arbor Healthcare System. The study was funded internally by UMHS.

Reference: JGIM, Vol. 19, June 2004, pp. 638-645.

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