March 11, 2018

ARTEMIS Investigates If Reducing Copayments Could Improve Adherence to Medication Therapy After Heart Attacks

March 11, 2018—Findings from the ARTEMIS study were presented by Tracy Wang, MD, in a Late Breaking Trial session at the American College of Cardiology's (ACC) 67th annual scientific session held March 10–12 in Orlando, Florida. ARTEMIS is a large, prospective, multicenter trial that aimed to examine how copayment vouchers affect patient adherence to recommended medical therapy.

The study demonstrated that when patients who had a heart attack were given vouchers to cover their copayments for medication to prevent a recurrence, physicians were more likely to prescribe a more effective, branded drug and patients were more likely to continue taking the medication for a full year as recommended in treatment guidelines. Additionally, the study found no significant differences between patient groups for the study's coprimary endpoint of the combined rate of heart attack, stroke, or death from any cause.

In the ACC press release, Dr. Wang commented, "The study met its primary endpoint of improving adherence to guideline-recommended therapy at 1 year. When affordability was not an issue, physicians felt less restrained in their ability to choose medications, and patients were 16% less likely to prematurely stop taking the medication." Dr. Wang is Associate Professor of Medicine at Duke University Medical School in Durham, North Carolina.

The background of the study is that current guidelines recommend use of antiplatelet medication for at least 1 year after a heart attack. Previous studies suggested that adherence to this treatment regimen begins to drop off after a few months, and by 1 year ,more than one-third of patients are no longer taking their medication. Other studies have suggested that cost is a major reason that some patients stop taking prescribed medications. At least one previous study showed that treatment adherence improved when patients received their medications at no charge.

As summarized in the ACC announcement, the ARTEMIS trial enrolled 11,001 patients treated for a heart attack at one of 301 hospitals in the United States. All patients had health insurance: 64% had private insurance, 42% were on Medicare, and 9% were on Medicaid. Seventeen percent of patients reported previously not filling a prescription because of the medication's cost.

The study randomly assigned participating hospitals to either the intervention or usual care arm of the study. At all participating hospitals, doctors used their clinical judgment to decide whether to prescribe clopidogrel or ticagrelor for each patient. At the intervention hospitals, but not at the usual care hospitals, patients received vouchers that waived the copay for their prescribed antiplatelet medication for 1 year.

Clopidogrel is available as a generic medication, the newer and more potent antiplatelet agent ticagrelor is currently available only as a branded product. Many patients have higher out-of-pocket costs for the same supply of a brand name drug versus the generic version.

The study's coprimary endpoints were continued use of the prescribed antiplatelet drug at 1 year without a gap in use of 30 days or more and the combined rate of heart attack, stroke, or death from any cause.

Because previous studies suggested that patients may report higher rates of treatment adherence than they actually achieve, the investigators validated patient reports by analyzing pharmacy records of the prescriptions filled by 8,360 patients and by periodically testing for blood levels of the medication in a subset of 944 patients.

Among patients who received vouchers, 87% reported taking their medication as prescribed, compared with 84% of the patients who received usual care. By contrast, the analysis of pharmacy records showed an adherence rate of 55% for the patients receiving vouchers compared with 46% for those receiving usual care. In the subset of patients who had their blood tested, 92% in the voucher group were adherent compared with 88% in the usual care group. All of these differences were statistically significant, advised Dr. Wang.

Dr. Wang stated in the ACC announcement, "While we know that patients often overestimate their own adherence, I was surprised by the size of the discrepancy between patient reports and pharmacy fill records. I suspect the 'true' answer is somewhere in between patient reports and pharmacy records, but both indicate that ensuring treatment adherence is still a huge problem."

Dr. Wang also noted that the study may have ended up with insufficient statistical power to identify a between-group difference for the coprimary endpoint because another surprising finding was that 28% of the patients who received vouchers chose not to use them.

She commented, "We used vouchers to reduce copayments because our patients were covered by multiple types of insurance and used a wide range of pharmacies and pharmacy benefit management services to obtain their medications. But vouchers only provide the intended copayment reduction if a patient chooses to or remembers to use it. Patients who never used the provided voucher had the highest rates of nonpersistence and adverse clinical outcomes."

She added that copayment reduction ultimately worked to improve medication prescription and use. "But our findings raise further questions about how best to deploy copayment reduction to effectively improve clinical outcomes, as well as how to consider copayment reduction strategies alongside other measures to improve patient adherence." The investigators they hope determine answers to these questions through additional analysis of the study data.


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