TY - JOUR
T1 - Effect of Medication Co-payment Vouchers on P2Y12 Inhibitor Use and Major Adverse Cardiovascular Events among Patients with Myocardial Infarction
T2 - The ARTEMIS Randomized Clinical Trial
AU - Wang, Tracy Y.
AU - Kaltenbach, Lisa A.
AU - Cannon, Christopher P.
AU - Fonarow, Gregg C.
AU - Choudhry, Niteesh K.
AU - Henry, Timothy D.
AU - Cohen, David J.
AU - Bhandary, Durgesh
AU - Khan, Naeem D.
AU - Anstrom, Kevin J.
AU - Peterson, Eric D.
N1 - Funding Information:
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 Information:
Funding/Support: This study was supported by
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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 11001 enrolled patients (median age, 62 years; 3459 [31%] women), 10102 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 10802 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.
AB - 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 11001 enrolled patients (median age, 62 years; 3459 [31%] women), 10102 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 10802 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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U2 - 10.1001/jama.2018.19791
DO - 10.1001/jama.2018.19791
M3 - Article
C2 - 30620370
AN - SCOPUS:85059701914
SN - 0098-7484
VL - 321
SP - 44
EP - 55
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 1
ER -