Association of a P2Y12 Inhibitor Copayment Reduction Intervention With Persistence and Adherence With Other Secondary Prevention Medications: A Post Hoc Analysis of the ARTEMIS Cluster-Randomized Clinical Trial

Abstract

Importance: The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) cluster-randomized trial found that copayment reduction for P2Y12 inhibitors improved 1-year patient persistence in taking that medication.

Objective: To assess whether providing copayment reduction for P2Y12 inhibitors increases patient persistence in taking other secondary prevention cardiovascular medications.

Design, setting, and participants: This post hoc analysis of the ARTEMIS trial includes data from 287 hospitals that enrolled patients between June 2015 and September 2016. Patients hospitalized with acute myocardial infarction were included. Data analysis occurred from May 2018 through August 2019.

Interventions: Hospitals randomized to the intervention provided patients vouchers that waived copayments for P2Y12 inhibitors fills for 1 year. Hospitals randomized to usual care did not provide study vouchers.

Main outcomes and measures: Persistence in taking β-blocker, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker medications at 1 year, defined as the absence of a gap in medication supply of 30 or more days by pharmacy fill data in the intervention-arm (intent-to-treat) population.

Results: A total of 131 hospitals (with 5109 patients) were randomized to the intervention, and 156 hospitals (with 3264 patients) randomized to the control group. Patients discharged from intervention hospitals had higher persistence in taking statins (2247 [46.1%] vs 1300 [41.9%]; adjusted odds ratio, 1.11 [95% CI, 1.00-1.24]), and β-blockers (2235 [47.6%] vs 1277 [42.5%]; odds ratio, 1.23 [95% CI, 1.10-1.38]), although the association was smaller than that seen for P2Y12 inhibitors (odds ratio, 1.47 [95% CI, 1.29-1.66]). Persistence in taking angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers were also numerically higher among patients in the intervention arm than in the usual-care arm, but this was not significant after risk adjustment (1520 [43.9%] vs 847 [40.5%]; adjusted odds ratio, 1.10 [95% CI, 0.97-1.24]). Patients in the intervention arm reported greater financial burden associated with medication cost than the patients in the usual-care arm at baseline, but these differences were no longer significant at 1 year.

Conclusions and relevance: Reducing patient copayments for 1 medication class increased persistence not only to that therapy class but may also have modestly increased persistence to other post-myocardial infarction secondary prevention medications. These findings have important implications for the clinical utility and cost-effectiveness of medication cost-assistance programs.

Trial registration: ClinicalTrials.gov identifier: NCT02406677.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Fanaroff reported a career development grant from the American Heart Association (grant 17FTF33661087), research grant support to the Duke Clinical Research Institute from Boston Scientific, and consulting fees from the American Heart Association. Dr Peterson reported receiving grants and/or personal fees from Bayer Pharmaceuticals, Amarin, Novo Nordisk, Amgen, Sanofi, Janssen Pharmaceuticals, AstraZeneca, Genentech, and the American Heart Association Get With the Guidelines–Stroke Analytic and has served as a consultant/advisory board member for Janssen, Boehringer Ingelheim, Sanofi, Bayer, Merck, AstraZeneca, Signal Path, and Livongo. 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 Aegerion, Alnylam, Amarin, Amgen, Arisaph, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Corvidia, Eisai, GlaxoSmithKline, Innovent, Janssen, Kowa, Lipimedix, Merck, Pfizer, Regeneron, Sanofi, and Takeda outside the submitted work. 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 the ARTEMIS trial from AstraZeneca. Dr Anstrom reported receiving a consulting honorarium from AstraZeneca and grants from the National Institutes of Health, Merck, and Bayer outside the submitted work. 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. Ms Fonseca and Dr Khan were employees of AstraZeneca during the time of study conduct. Dr Fonarow reported receiving consulting honoraria from Abbott, Amgen, AstraZeneca, Bayer, Janssen, and Novartis. 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. No other disclosures were reported.

Figures

Figure 1.. Study Flowchart

ARTEMIS indicates Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study.

Figure 2.. Adjusted Associations Between P2Y12 Inhibitor Copayment Reduction Intervention and Persistence and Adherence to Secondary Prevention Medications

Patients in the intervention arm had higher rates of persistence and adherence to non–P2Y12 inhibitor secondary prevention medications than the usual-care arm in both the intent-to-treat and as-treated arms. Results for the intent-to-treat population (A) and with patients who did not use vouchers excluded (B); the outcome of the intervention was greater when those who did not use vouchers were excluded. Variables for adjustment included hospital characteristics, demographic information, comorbidities, details of the index presentation and hospital course, and patient responses to baseline survey questions about quality of life and medication-taking behaviors. ACE indicates antiotengin-converting enzyme; ARB, angiotension II–receptor blocker.

Figure 3.. Adjusted Associations Between P2Y12 Inhibitor Copayment Reduction Intervention and Persistence and Adherence to Secondary Prevention Medications Among Patients Who Had Ever and Never Filled an Additional Cardiac Medication Prescription on the Same Day as a P2Y12 Inhibitor Prescription

There was no interaction observed between whether a patient had ever filled a non–P2Y12 inhibitor secondary prevention medication at the same time as a P2Y12 inhibitor and the observed association with persistence (A) or adherence (B) in taking other cardiovascular medications. Variables for adjustment included hospital characteristics, demographic information, comorbidities, details of the index presentation and hospital course, and patient responses to baseline survey questions about quality of life and medication-taking behaviors. ACE indicates antiotengin-converting enzyme; ARB, angiotension II–receptor blocker.