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Antiplatelet therapy adherence dropped in era with newer P2Y12 inhibitors
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From 2008 to 2016 — after the introduction of prasugrel and ticagrelor — the percentage of patients who did not fill a prescription for a P2Y12 inhibitor within 30 days of hospital discharge after PCI increased significantly, according to an analysis of administrative claims database from a national health insurer.
“Speaking from the perspective of an interventional cardiologist, these are extremely disturbing data,” study researcher Jay Giri, MD, MPH, director of peripheral intervention and assistant professor of medicine at the Hospital of the University of Pennsylvania and a Cardiology Today Next Gen Innovator, told Cardiology Today’s Intervention.
Not only is the rate of nonadherence troubling, he noted, but it is particularly concerning that the rate is so high among insured patients who have partial prescription drug coverage, which theoretically is the best-case scenario.
“Most interventional cardiologists are going to be surprised to know that a group of insured patients that’s nationally representative has such an incredibly high rate of never even filling the first script after we perform PCI,” he said.
Decreased adherence, increased costs
Guidelines have shifted toward recommending newer antiplatelet agents, including prasugrel (Effient, Daiichi Sankyo/Eli Lilly) and ticagrelor (Brilinta, AstraZeneca), over clopidogrel, but relatively little data exist on adherence to antiplatelet therapy with the introduction of these new medications, according to lead study author Elias J. Dayoub, MD, MPH, from the department of medicine at the Hospital of the University of Pennsylvania.
“In this study, we wanted to use real-world data to determine patient adherence, how it compares among the three agents and what the costs are,” he told Cardiology Today’s Intervention. “During this time period, clopidogrel became generic, whereas prasugrel and ticagrelor are both on patent and relatively expensive.”
Dayoub, Giri and colleagues evaluated data on 55,340 patients who underwent PCI from 2008 to 2016 from the OptumInsight Clinformatics Data Mart database, which included members of UnitedHealthcare. They found that the rate of primary nonadherence — defined as not filling a P2Y12 inhibitor prescription within 30 days of hospital discharge — increased from 6.4% to 19.1% during the study period (P < .001).
Notably, primary nonadherence was most frequent among patients who resided in ZIP codes with a mean net worth between $25,000 and $149,999. The researchers also found that primary nonadherence increased from 10.8% in 2008 to 15.7% in 2016 in the lowest net worth communities (P = .01), but decreased from 13.6% to 9.8% in the highest net worth communities (P = .03).
Results also showed that the mean copayments per 6 months’ supply were higher for patients who were prescribed prasugrel and ticagrelor compared with clopidogrel ($287, $265 and $132, respectively; P < .001). At 12 months, mean total copayments remained higher for ticagrelor and prasugrel vs. clopidogrel ($557, $556 and $251; P < .001).
Additionally, at 6 months, patients who filled a clopidogrel prescription after discharge had a greater mean medication possession ratio than those who filled prasugrel or ticagrelor prescriptions (0.85, 0.79 and 0.76, respectively; P < .001). Mean medication possession ratios decreased among all groups at 12 months, but remained higher among patients who filled a prescription for clopidogrel compared with prasugrel and ticagrelor (0.76, 0.71 and 0.68, respectively; P < .001).
Important of social determinants
In light of their findings, Dayoub said the higher costs of prasugrel and ticagrelor appear to be the most likely culprits behind primary nonadherence. Whereas other factors, such as medication side effects, may affect long-term adherence, cost is the only upfront factor to which patients are exposed and may therefore explain why some patients never fill a P2Y12 inhibitor prescription, he noted.
In an invited commentary, Julie C. Lauffenburger, PharmD, PhD, and Niteesh K. Choudhry, MD, PhD, both from Brigham and Women’s Hospital and Harvard Medical School, wrote that “the classical view” of nonadherence blames the patient’s stubbornness or carelessness.
“However, the perception that nonadherence results only from patients’ failure to follow instructions is an inadequate explanation for what is, more fairly, a complex behavioral process,” they wrote. “Poor adherence results from multiple barriers, many of which patients cannot control.”
The study, which identifies the scope of the problem of nonadherence, is a first step toward addressing the issue, but more will need to be done, according to Dayoub.
“It’s challenging for prescribers to be totally mindful of how much these medications are going to cost different patients,” he said. “Certainly, if there’s a way to make these prices more transparent — to know what the out-of-pocket costs for patients will be upfront — that could help guide our decision-making.”
These other factors, including costs or difficulty in obtaining these drugs from pharmacies, should also be seen as part of the precision medicine equation, Giri noted.
“We often talk about precision medicine in the context of personalizing therapy based on clinical risk scores or novel genetic risk information or pharmacogenomics, but what we found with this study is that maybe the most relevant personalizing factor in making therapies more precise and may have the greatest impact on public health is accounting for the social determinants of health that surround an individual patient, including access to care, access to these drugs and the costs associated with them,” he said. – by Melissa Foster
For more information:
Elias J. Dayoub, MD, MPP, can be reached at elias.dayoub@uphs.upenn.edu.
Jay Giri, MD, MPH, can be reached at giri.jay@gmail.com.
Disclosures: The authors report no relevant financial disclosures. Lauffenburger reports she has received salary support for unrestricted grants from Sanofi and AstraZeneca. Choudhry reports he has received unrestricted research grants to study medication adherence from Sanofi, AstraZeneca, Merck and Medisafe, and he is a consultant to and holds equity in Ontiq Inc.
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