Modest, at best: The effect of getting rid of copays for antiplatelet drugs

A study designed to test whether eliminating copays would improve adherence to antiplatelet therapy showed that, yes, indeed, it does. But the results also showed no reduction in major cardiovascular events among those who stuck with the medication.

Peter Wehrwein

A study designed to test whether eliminating copays would improve adherence to antiplatelet therapy showed that, yes, indeed, it does.

But that takeaway came with a “so what” chaser. The study results also showed no reduction in major cardiovascular events among those who stuck with the medication.

There are some plausible explanations for the disconnect between adherence and outcome. Still, the results sprinkle some fresh question marks into the narrative that getting rid of copays and improving adherence will lead to better outcomes.

Results from the AstraZeneca-funded study were reported in the Jan. 1/8, 2019, edition of JAMA. Led by researchers at Duke, ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) was a massive undertaking that enrolled 11,000 heart attack patients at 301 American hospitals. The randomization was done by hospital, rather than by patient, partly because the researchers figured that patient randomization would lead to high withdrawal rates.

Before they were discharged, patients at the 135 hospitals randomized to the intervention group were given vouchers for generic clopidogrel (Plavix) or Astra­Zeneca’s brand-name antiplatelet drug, Brilinta (ticagrelor). The vouchers covered the entire cost of the drugs for people covered by Medicare or Medicaid (because those programs don’t allow copay assistance) or charged the copay to the study. Either way, for the patient, the voucher eliminated the copay and any out-of-pocket expense for the antiplatelet medication for a year. Patients in the “usual care” group didn’t get a voucher, so they paid copays as usual. Doctors were free to prescribe a third antiplatelet drug, Effient (prasugrel), but the study didn’t include vouchers for Effient.

The researchers, led by Tracy Y. Wang, MD, of Duke Clinical Research Institute, measured adherence in a number of ways but the main one was continued use (i.e., no gap of 30 days or longer) of antiplatelet medication at 3, 6, 9, and 12 months. The results show that “medication persistence”—as the researchers call it—for patients in the intervention group was 87% vs. 83.8% in the control group. That’s not a huge difference, but it passed the muster of statistical significance.

When researchers looked at another primary endpoint, major adverse cardiovascular events, they found a difference (10.2% in the intervention group vs. 10.6% in the usual care group), but it was deemed a tie once various statistical adjustments were made.

Other studies have shown that copays affect adherence. According to an editorial that accompanied the study, copays for clopidogrel range from $47 to $203 per month; for Brilinta, they range from $53 to $387. At that level, you might expect the elimination of copays to have more of an effect. The researchers noted that some patients in the control group might have taken advantage of voucher programs outside of the study, thereby diluting the difference between the two groups. Another wrinkle: A surprising proportion (28%) of the people in the intervention group didn’t use the vouchers. Reasons for not doing so included losing the physical voucher card and the pharmacy not accepting the voucher.

It is conjecture but there are explanations for adherence not adding up to better outcomes. Antiplatelet drugs are just one of the drugs that people take after a heart attack. Nudging adherence up a notch for one drug may not have much of an effect.

The editorial by Cynthia Jackson of the Western University of the Health Sciences in Pomona, Calif., and Dennis Ko, MD, of the University of Toronto, says the voucher program costs up to $1,600 per patient per year. It’s fair to ask whether that is money well spent if outcomes didn’t improve and adherence, by only a smidgen.