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

Contribution To Literature:

The ARTEMIS trial showed that, while copayment reduction significantly affected clinician’s choice of P2Y12 inhibitor use post-ACS presentation and improved patient persistence with treatment, it did not impact clinical outcomes at 1 year.


The goal of the trial was to compare the efficacy of copayment intervention on P2Y12 inhibitor use among acute coronary syndrome (ACS) patients and outcomes at 1 year.

Study Design

Patients presenting with ACS underwent 1:1 cluster randomization to either copay intervention (n = 131 sites, 6,135 patients) or usual care (n = 166 sites, 3,967 patients). P2Y12 inhibitor choice and duration of therapy were determined by the treating physicians. Enrolled patients could be treated with any P2Y12 inhibitor. Intervention site patients provided a copayment voucher card for either a generic (clopidogrel) or brand (ticagrelor) P2Y12 inhibitor. No other interventions to improve adherence were given.

Inclusion criteria:

  • ST-segment elevation myocardial infarction (STEMI) or NSTEMI patients on P2Y12 inhibitor therapy
  • Enrolled before discharge
  • US-based health insurance (commercial or government)
  • Total number of enrollees: 10,102
  • Duration of follow-up: 1 year
  • Mean patient age: 62 years
  • Percentage female: 32%

Other salient features/characteristics:

  • STEMI: 46%
  • Diabetes: 32%
  • Home aspirin use: 43%, home P2Y12 inhibitor use: 14%
  • Percutaneous coronary intervention (PCI) during index MI: 89%
  • Discharge P2Y12 inhibitor use among copay intervention vs. usual care arm: clopidogel 36.0% vs. 54.7%, ticagrelor 59.6% vs. 32.4%, p < 0.001

Principal Findings:

The primary outcome, patient-reported nonpersistence (≥30-day gap) in P2Y12 inhibitor use, for copay intervention vs. usual care, was 13.0% vs. 16.2%, p < 0.0001; adjusted odds ratio 0.84 (95% confidence interval 0.72-0.98).

  • Based on pharmacy fills: 44.8% vs. 53.7%, p < 0.0001
  • Major adverse cardiac events (MACE): 10.2% vs. 10.6%, p = 0.65

Secondary outcomes:

  • Death: 3.9% vs. 3.9%, p = 0.98
  • Recurrent MI: 6.9% vs. 7.3%, p = 0.64

Among patients in the intervention arm who actually used the voucher (72% of total), MACE was 10% vs. 16.2%, p < 0.001.

Medication persistence data (n = 8,373): Compared between patient-reported and pharmacy refill data. One-year medication nonpersistence was higher with pharmacy refill data (48.3%) than patient self-report (15.3%). In total, 26.9% in the intervention arm who self-reported persistence were found to be nonpersistent, while 20.4% classified as nonpersistent by pharmacy fill data were actually persistent. MACE rates were highest among patients who were nonpersistent by both methods.


The results of this trial indicate that while copayment reduction significantly affected clinician’s choice of P2Y12 inhibitor use post-ACS presentation and improved patient persistence with treatment, it did not impact clinical outcomes at 1 year. Further, even among patients who were in the intervention arm, nearly one in three did not use their vouchers.

These results are similar to the MI FREEE trial, where providing medication free (no copayment) for statins, beta-blockers, and angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker to patients recently discharged with an MI improved medication adherence and lowered patient costs, but did not improve patient outcomes. This further reinforces that copayment reduction/elimination should be part of a multi-pronged strategy to enhance medication persistence and outcomes, rather than as a solution set in itself.


Fanaroff AC, Peterson ED, Kaltenbach LA, et al. Agreement and Accuracy of Medication Persistence Identified by Patient Self-report vs Pharmacy Fill: A Secondary Analysis of the Cluster Randomized ARTEMIS Trial. JAMA Cardiol 2020;Mar 4:[Epub ahead of print].

Presented by Dr. Tracy Wang at the American College of Cardiology Annual Scientific Session (ACC 2018), Orlando, FL, March 11, 2018.

Keywords: ACC18, ACC Annual Scientific Session, Acute Coronary Syndrome, Adenosine, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Insurance, Health, Medication Adherence, Myocardial Infarction, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Treatment Outcome

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