Related Experiment Video
Updated: Jan 31, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Effect of Medication Co-payment Vouchers on P2Y12 Inhibitor Use and Major Adverse Cardiovascular Events Among
Tracy Y Wang1, Lisa A Kaltenbach1, Christopher P Cannon2
1Duke Clinical Research Institute, Durham, North Carolina.
Insights
Removing co-payment barriers for P2Y12 inhibitors increased medication persistence in myocardial infarction (MI) patients. However, this intervention did not significantly reduce major adverse cardiovascular events (MACE) within one year.
Area of Science:
- Cardiovascular Medicine
- Clinical Trials
- Health Economics
Background:
- Many patients discontinue P2Y12 inhibitor therapy prematurely after myocardial infarction (MI), contrary to guidelines.
- Higher-potency P2Y12 inhibitors are underutilized, with cost often cited as a primary reason.
- Understanding the impact of financial barriers on medication adherence is crucial for improving cardiovascular outcomes.
Purpose of the Study:
- To evaluate if eliminating co-payment costs for P2Y12 inhibitors improves patient adherence to therapy.
- To assess the effect of reduced financial burden on major adverse cardiovascular events (MACE) in post-MI patients.
Main Methods:
- A cluster randomized clinical trial involving 301 hospitals and over 11,000 adult patients with acute MI.
- Intervention group hospitals provided co-payment vouchers for P2Y12 inhibitors (clopidogrel or ticagrelor) for one year.
- Control group received usual care without study-provided vouchers; outcomes were assessed at one year post-discharge.
Main Results:
- Patient-reported persistence with P2Y12 inhibitors was significantly higher in the intervention group (87.0%) compared to the usual care group (83.8%), an absolute increase of 3.3%.
- Despite improved persistence, there was no statistically significant difference in the composite outcome of MACE (death, recurrent MI, or stroke) at one year between the two groups.
- Approximately 72% of patients in the intervention group utilized the co-payment vouchers.
Conclusions:
- Provision of co-payment vouchers for P2Y12 inhibitors effectively increases medication persistence in patients following MI.
- Financial incentives alone may not be sufficient to reduce major adverse cardiovascular events, suggesting other factors influence MACE.
- Addressing medication cost barriers is important for adherence but requires a multifaceted approach to impact clinical event rates.
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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