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Effect of Medication Co-payment Vouchers on P2Y12 Inhibitor Use and Major Adverse Cardiovascular Events Among Patients With Myocardial InfarctionThe ARTEMIS Randomized Clinical Trial

Educational Objective
To understand that co-payments may be barriers to medication adherence.
1 Credit CME
Key Points

Question  What is the effect of vouchers to offset the co-payment costs for P2Y12 inhibitors on medication persistence and major adverse cardiovascular events (MACE) among patients with acute myocardial infarction?

Findings  In this cluster randomized trial conducted at 301 hospitals that enrolled 11 001 adult patients with acute myocardial infarction, provision of vouchers to offset the cost of medication co-payments for P2Y12 inhibitors significantly increased patient-reported medication persistence through 1 year (87.0% vs 83.8%), but there was no significant difference in 1-year MACE outcomes (hazard ratio, 1.07).

Meaning  Providing co-payment assistance for P2Y12 inhibitor medications after myocardial infarction increased persistence with a guideline-recommended therapy but did not improve clinical outcomes at 1 year.


Importance  Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations.

Objective  To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE).

Design, Setting, and Participants  Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion.

Interventions  Hospitals randomized to the intervention (n = 131 [6436 patients]) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 [25th-75th percentile, $20-$339]). Hospitals randomized to usual care (n = 156 [4565 patients]) did not provide study vouchers.

Main Outcomes and Measures  Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor.

Results  Among 11 001 enrolled patients (median age, 62 years; 3459 [31%] women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 [36.0%] in the intervention group and 2497 [54.7%] in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 [87.0%] vs 3324/3967 [83.8%], respectively; P < .001; adjusted difference, 2.3% [95% CI, 0.4% to 4.1%]; adjusted odds ratio, 1.19 [95% CI, 1.02 to 1.40]). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% [95% CI, −0.73% to 2.06%]; adjusted hazard ratio, 1.07 [95% CI, 0.93 to 1.25]).

Conclusions and Relevance  Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes.

Trial Registration  ClinicalTrials.gov Identifier: NCT02406677

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Article Information

Corresponding Author: Tracy Y. Wang, MD, MHS, MSc, Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27705 (tracy.wang@duke.edu).

Accepted for Publication: November 20, 2018.

Author Contributions: Dr Wang and Ms Kaltenbach had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Wang, Cannon, Fonarow, Choudhry, Henry, Cohen, Bhandary, Khan, Anstrom, Peterson.

Acquisition, analysis, or interpretation of data: Wang, Kaltenbach, Cannon, Fonarow, Henry, Bhandary, Khan, Anstrom, Peterson.

Drafting of the manuscript: Wang, Khan.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Wang, Kaltenbach, Cannon, Bhandary, Anstrom.

Obtained funding: Wang, Bhandary, Khan, Peterson.

Administrative, technical, or material support: Wang, Cannon, Bhandary, Khan.

Supervision: Wang, Cannon, Bhandary, Khan, Peterson.

Conflict of Interest Disclosures: Dr Wang reported receiving research grant support to the Duke Clinical Research Institute from Amgen, AstraZeneca, Bristol-Myers Squibb, Cryolife, Novartis, Pfizer, Portola, and Regeneron and receiving consulting honoraria from Grifols and Gilead. Dr Cannon reported receiving research grant support from Amgen, Arisaph, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, and Takeda and receiving consulting honoraria from Alnylam, Amarin, Amgen, Arisaph, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Janssen, Kowa, Lipimedix, Merck, Pfizer, Regeneron, Sanofi, and Takeda. Dr Fonarow reported receiving consulting honoraria from Amgen, AstraZeneca, Bayer, Janssen, and Novartis. Dr Choudhry reported receiving research grant support to Brigham and Women’s Hospital from Merck, Sanofi, AstraZeneca, CVS Health, and Medisafe Inc. Dr Henry reported receiving a steering committee honorarium for ARTEMIS from AstraZeneca. Dr Cohen reported receiving research grant support from AstraZeneca, Merck, Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific and receiving consulting honoraria from Medtronic and Edwards Lifesciences. Dr Anstrom reported receiving a consulting honorarium from AstraZeneca. Dr Peterson reported receiving grants and/or personal fees from Bayer Pharmaceuticals, Janssen Pharmaceuticals, AstraZeneca, Genentech, and the American Heart Association GWTG–Stroke Analytic and has served as a consultant/advisory board member for Janssen, Boehringer Ingelheim, Sanofi, Bayer, Merck, AstraZeneca, Signal Path, and Venable. No other disclosures were reported.

Funding/Support: This study was supported by a research grant from AstraZeneca to the Duke Clinical Research Institute.

Role of the Funder/Sponsor: Funding for the study was provided by AstraZeneca. The trial protocol and data collection forms were designed and written by the academic investigators. Duke Clinical Research Institute (DCRI, Durham, North Carolina) served as the coordinating center and was responsible for all study data collection and analyses. AstraZeneca collaborated in the design of the study and reviewed and approved the manuscript before submission of the manuscript for publication. The final decision for manuscript submission was made by the academic investigators; the sponsor did not have a right to veto such a decision.

Disclaimer: Dr Peterson, associate editor of JAMA, was not involved in the editorial review of or decision to publish this article.

Data Sharing Statement: See Supplement 4.

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