Co-Pay Vouchers Boost P2Y12 Inhibitor Use but Don't Cut Cardiovascular Events

January 9, 2019

By Will Boggs MD

NEW YORK (Reuters Health) - Co-payment vouchers to cover the cost of a P2Y12 inhibitor for one year improve adherence to these medications among patients with myocardial infarction, but do not lead to reductions of major adverse cardiovascular events (MACE), according to results from the ARTEMIS trial.

"Adherence to evidence-based therapies is still a major problem," Dr. Tracy Y. Wang from Duke Clinical Research Institute, in Durham, North Carolina, told Reuters Health by email. "Tackling cost is very important and improves medication adherence, but is not enough. We need to provide clinician decision-making tools to promote guideline awareness and adherence, and we need to consider other patient-centered strategies to partner effectively for secondary prevention."

The American College of Cardiology/American Heart Association and the European Society of Cardiology recommend one year of P2Y12-inhibitor therapy after myocardial infarction and favor ticagrelor or prasugrel over clopidogrel for patients without a high risk of bleeding.

Generic clopidogrel has been available since 2012, whereas ticagrelor and prasugrel (non-generic through October 2017) have higher out-of-pocket costs.

Dr. Wang and colleagues investigated whether removing co-pay barriers increases P2Y12 adherence and reduces the risk of MACE in their trial of 6,436 patients from 131 hospitals randomized to the intervention and 4,565 patients from 156 hospitals randomized to usual care.

Within one year of discharge, 85.8% of patients reported persistence with P2Y12 inhibitor therapy, with significantly higher rates in the voucher group (87.0%) than in the usual-care group (83.8%), the researchers report in the January 1/8 issue of JAMA.

Pharmacy-defined persistence rates through one year, although lower than patient-reported rates, remained significantly higher in the voucher group (55.2%) than in the usual care group (46.3%).

MACE rates did not differ significantly between the intervention group (10.2%) and the usual-care group (10.6%).

At discharge, 36.0% of patients in the intervention group and 54.7% of patients in the usual-care group were prescribed clopidogrel. In contrast, ticagrelor was prescribed for 59.6% of patients in the intervention group and 32.4% of patients in the usual-care group. Prasugrel was prescribed for 4.4% and 12.9%, respectively.

In the first year after discharge, only 72% of patients in the intervention group used their co-pay voucher at least once. Medication persistence was significantly higher among those who used their vouchers, and unadjusted MACE rates were significantly lower (7.49% vs. 17.20%).

"Clinicians are frequently told by patients that medication cost is a major driver of non-adherence, and we expend so many resources in our practices to help patients overcome this particular barrier," Dr. Wang said. "This study tells us that while cost is a key barrier, and alleviating this can improve medication adherence, it is still not enough in getting patients to 100% adherence and improving clinical outcomes."

Dr. Cynthia A. Jackevicius from Western University of Health Sciences, College of Pharmacy, in Pomona, California, who co-authored an accompanying editorial, told Reuters Health by email, "We proposed several potential reasons for the lack of change in MACE rates in our editorial. Some of these include: a) suboptimal use of the co-pay voucher by patients which may have blunted the strength of the intervention; b) low magnitude of adherence (in both groups) which may have prevented reaching a high enough antiplatelet threshold for an improved treatment effect; and c) more ticagrelor was used in the intervention group - unique drug characteristics of ticagrelor (shorter duration, and reversible nature of ticagrelor effect) compared with clopidogrel may have magnified the negative impact of nonadherence in the intervention group."

"A high co-pay may be one barrier for patients, but it is likely that there are multiple reasons for nonadherence," she said. "Engaging with patients in shared decision-making and understanding patient preferences and values are crucial first steps in tackling medication adherence."

Trond Roeed Pettersen from Haukeland University Hospital, in Bergen, Norway, who recently reviewed the challenges of adhering to medications following first-time percutaneous coronary intervention, told Reuters Health by email, "This report underlines the importance of recognizing medication adherence and persistence as complex phenomena. To improve medication adherence as well as persistence, several potential barriers must be considered and targeted."

"It is interesting that those who actually used the voucher had a reduced risk of cardiovascular events," said Pettersen, who was not involved in the trial. "The effect of the vouchers disappeared after adjustment for a number of other factors. This implies the possibility that use of vouchers is associated with other factors that have a significant influence on risk for cardiovascular events."

Dr. Elias J. Dayoub from Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, who has also researched trends in P2Y12-inhibitor use and adherence, told Reuters Health that these results "offer compelling evidence that medication costs or co-payments are not the sole contributor to P2Y12-inhibitor nonadherence after MI, and that several behavioral and systemic causes are contributing as well."

"Among the more surprising trial findings was that nearly 30% of patients assigned to the co-payment-voucher group never used the voucher made available to them," he said. "Patients in the intervention group who did not use the voucher had lower adherence and higher rates of MACE compared to patients who did use vouchers as well as the control group. As the authors note, co-payment vouchers require patient activation, and many of the reasons for voucher nonuse are the same as the barriers leading to medication nonadherence."


JAMA 2019.

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