D ATA D R I V E N . P O L I C Y F O C U S E D LDI ResearchBRIEF Research to Improve the Nation’s Health System 2018 . No. 12 TRENDS IN P2Y12 RECEPTOR INHIBITOR USE AND ADHERENCE AFTER PERCUTANEOUS CORONARY INTERVENTION, 2008-2016 Elias J. Dayoub, Matthew Seigerman, Sony Tuteja, Taisei Kobayashi, Daniel Kolansky, Jay Giri, Peter Groeneveld JAMA Internal Medicine — May 2018 KEYFINDINGS Post-angioplasty, patient adherence to recommended antiplatelet therapy decreased when newer, more expensive drugs were introduced. From 2008-2016, as the use of newer agents increased, the proportion of patients not filling any antiplatelet prescription within 30 days of discharge increased from 6.4% to 19.1%. In the subsequent 12 months, the newer drugs were associated with higher patient costs and lower adherence to recommended therapy. THE QUESTION THE FINDINGS Percutaneous coronary intervention (PCI), or angioplasty, is a In this study of 55,340 patients who underwent PCI from 2008 to 2016, the procedure that reopens blocked coronary arteries in patients with acute proportion of patients filling a prescription for clopidogrel within 30 days coronary syndrome. Almost all patients receive a stent, a small metal of discharge decreased from 93.6% to 44%, while the proportion filling a mesh that help keep the artery open. After PCI, patients must take prescription for prasugrel or ticagrelor increased from zero to 36.9% antiplatelet therapy for 6-12 months to help prevent blood clots from (Figure 1). During the same period, the proportion of patients who did not forming, thereby reducing the likelihood of stroke, myocardial infarction, fill any P2Y12 inhibitor prescription within 30 days increased from 6.4% to or cardiovascular deaths. 19.1%. Patients not filling a prescription were less likely to be white, less likely to be male, and more likely to reside in the Southern United States. Current guidelines recommend two newer, more expensive antiplatelet agents—prasugrel and ticagrelor—over an earlier one, clopidogrel. Patients filling a prescription for clopidogrel had an average copayment of Although there are some clinical trade-offs, the newer agents have been $21.40 for a 30-day supply, compared to $48.10 for prasugrel and $48.60 shown to be more efficacious in preventing serious adverse outcomes. for ticagrelor. Patients who did not fill a P2Y12 inhibitor prescription within 30 days of discharge more frequently lived in areas with less household To be effective, drugs must be used. Adherence has been a problem in net worth. The proportion of non-adherent patients from the lowest net antiplatelet therapy, with 12-month adherence rates varying from 30% worth communities increased from 2008 to 2016 (10.8% to 15.7%), while the to 90%. Did the introduction of newer P2Y12 inhibitors affect adherence proportion decreased from the highest worth communities (13.6% to 9.8%) to antiplatelet therapy? The authors used a large commercial claims (Figure 2). database to assess use, trends, costs, and adherence rates for all three agents from 2008-2016, an interval that spans FDA approval for Nearly 80% of patients received a drug-eluding stent, where antiplatelet prasugrel (July 2009) and ticagrelor (July 2011). therapy is recommended for 12 months. In these patients, continuing adherence largely mirrored that of the initial fill, with patients less likely to continue prescriptions for the newer medications. At six months, patients who filled clopidogrel had the medication available 85% of the time, COLONIAL PENN CENTER | 3641 LOCUST WALK | PHILADELPHIA, PA 19104-6218 | LDI.UPENN.EDU | P: 215-898-5611 | F: 215-898-0229 | @PENNLDI ResearchBRIEF LDI compared to 79% for prasugrel and 76% for ticagrelor. At 12 months, Figure 1. Percentage of patients who underwent PCI and filled a these percentages dropped to 76%, 71%, and 68%, respectively. At 12 prescription for clopidogrel, prasugrel, and ticagrelor within 30 days of months, ticagrelor had the highest average copayments, $557, compared discharge, 2008-2016. to prasugrel ($556) and clopidogrel ($251). Nonadherence was associated with poorer six-month outcomes, included recurrent acute coronary syndrome and hospitalizations for bleeding. THE IMPLICATIONS One implication of this study is that the introduction of new drugs may have exacerbated socioeconomic health disparities. Increased prescribing of new, more expensive agents can affect health outcomes by worsening adherence among patients with low socioeconomic status, thereby putting them at risk for further cardiovascular events. Patients were less likely to fill prescriptions for newer P2Y12 inhibitors, and less likely to continue to fill these prescriptions. The newer drugs partially replaced a lower-cost generic, resulting in higher Figure 2. Community mean household net worth in patients who out-of-pocket costs for patients. The most financially disadvantaged underwent PCI and did not fill any prescription for any P2Y12 inhibitor within patients had higher rates of nonadherence, and nonadherence rates 30 days of discharge. among those patients increased from 2008-2016. This suggests that increased prescribing of the newer, more expensive P2Y12 inhibitors may be contributing to higher rates of nonadherence. THE STUDY The authors used administrative claims data from UnitedHealthcare to identify patients aged 18-64 hospitalized for PCI from January 1, 2008 to December 1, 2016. They identified filled prescriptions for a P2Y12 inhibitor from pharmacy claims. They grouped patients by type of P2Y12 inhibitor and compared baseline characteristics such as demographics, region, and household net worth. They measured the proportion of patients filling prescriptions for P2Y12 inhibitors within 30 days of discharge for each year. To assess whether patients continued to fill prescriptions, the authors looked at nonadherence in patients receiving drug-eluting stents, where P2Y12 inhibitors are indicated for 12 months. They Dayoub EJ, Seigerman M, Tuteja S, et al. Trends in Platelet Adenosine measured rates of recurrent acute coronary syndrome and bleeding Diphosphate P2Y12 Receptor Inhibitor Use and Adherence Among Antiplatelet- complications for each P2Y12 inhibitor, and compared patients’ out-of- Naive Patients After Percutaneous Coronary Intervention, 2008-2016. JAMA pocket costs across the agents. Intern Med. Published online May 21, 2018. doi:10.1001/jamainternmed.2018.0783 LEAD AUTHOR DR. ELIAS DAYOUB Elias Dayoub, MD, MPP is a National Clinician Scholar and VA Scholar at the University of Pennsylvania. He completed his internal medicine residency at Penn, after obtaining his medical degree from the University of Michigan and a Master in Public Policy from Harvard. Prior to beginning his medical training, he worked for an economic consulting firm advising clients in government and industry on cost issues in health care. His research focuses on how the adoption of innovations in cardiovascular pharmacotherapies and medical devices affects health care utilization and costs, as well as access to care and health disparities. Additionally, he explores policy solutions to address the economic and social implications of medical innovation.