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Reduced co-payment boosts physician, patient adherence to antiplatelet therapy after MI
ORLANDO, Fla. — The use of vouchers to reduce out-of-pocket costs for brand-name and generic antiplatelet medications improved physician and patient adherence to guideline-directed treatment after MI, according to data from the ARTEMIS trial.
Improved adherence, however, did not translate to better clinical outcomes, Tracy Y. Wang, MD, MHS, MSc, FACC, FAHA, associate professor of medicine at Duke University Medical School, said during a presentation at the American College of Cardiology Scientific Session.
In the unblended, cluster-randomized trial, clopidogrel was prescribed less frequently at sites where patients received vouchers to cover antiplatelet medications compared with those where patients did not receive vouchers (26% vs. 54.7%; P < .0001), whereas ticagrelor (Brilinta, AstraZeneca; 36% vs. 32.4%; P < .0001) was prescribed more often in the voucher arm.
“This suggests that more physicians were prescribing higher potency P2Y12 inhibitors when affordability was not part of the equation,” Wang said.
Additionally, patients in the co-payment intervention arm vs. the usual-usual care arm reported being less likely to be non-persistent to medication and stop treatment before 1 year (12.96% vs. 16.21%; unadjusted OR = 0.76; 95% CI, 0.65-0.89; adjusted OR = 0.72-0.98).
In secondary analyses, patients in the intervention arm were less likely to cease medication use before 1 year as assessed by pharmacy fills (44.8% vs. 53.71%; unadjusted OR = 0.64; 95% CI, 0.57-0.73; adjusted OR = 0.68; 95% CI, 0.6-0.77) and blood metabolite levels (8.23% vs. 12.35%; unadjusted OR = 0.64; 95% CI, 0.42-0.98).
Despite improved physician and patient adherence to guideline-recommended therapy, however, patients in the intervention arm were not less likely to experience MACE — a composite of death, recurrent MI and stroke within 1 year — than patients in the usual-care arm (10.17% vs. 10.63%; unadjusted OR = 0.96; 95% CI, 0.8-1.15; adjusted OR = 1.07; 95% CI, 0.93-1.25).
There were also no significant differences in the incidence of the individual components of the primary endpoint between the two study groups.
Of note, Wang said, 28% of the intervention arm did not use the study voucher. In comparisons of patients in the intervention group who used the voucher, those in the intervention group who did not use the voucher and those in the usual-care arm, patients who did not use the voucher had the highest rates of non-persistence. In these analyses, patients who used the voucher were significantly less likely than the usual-care arm to stop medication use before 1 year, even after adjustment (adjusted OR = 0.65; 95% CI, 0.55-0.78).
Similarly, the MACE rate at 1 year was highest among patients in the intervention arm who did not use the voucher, and patients who used the voucher vs. the usual-care arm were less likely to experience MACE (unadjusted HR = 0.7; 95% CI, 0.58-0.84). However, the difference was no longer statistically significant after adjustment (adjusted HR = 0.9; 95% CI, 0.76-1.08), Wang said.
ARTEMIS included 301 U.S. hospitals and 11,001 patients (mean age, 62 years; 32% women) with STEMI or non-STEMI. A total of 135 sites with 6,436 patients were randomly assigned to the intervention and 166 sites with 4,565 patients were assigned to usual care. All patients had health insurance with prescription coverage, and treatment was at the discretion of the physician.
Although the co-payment intervention affected physician prescribing patterns and improved patient persistence to treatment, important questions remain, according to Wang.
“We have to ask ourselves : Why was the intervention not enough to change clinical outcomes? In part, this may be because the intervention targeted only a single drug class with modest co-pay differences between brand and generic therapies. Also, there was a high level of persistence to treatment at baseline, showing that we are already paying attention to this in routine clinical practice,” Wang said.
“Broader-scale interventions are likely needed to further improve medication persistence and patient outcomes and we should consider co-payment reduction as part of a multi-pronged strategy to enhance medication persistence and outcomes.” – by Melissa Foster
Reference:
Wang T. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.
Disclosure: The study was sponsored by AstraZeneca. Wang reports she has received consultant fees/honoraria from Gilead, Merck and Sanofi, and research grants from AstraZeneca, Boston Scientific, Bristol-Myers Squibb, Eli Lilly/Daiichi Sankyo Alliance, Gilead, Novartis, Pfizer and Regeneron.
Perspective
Back to TopThis was an outstanding study that for me, as a pharmacist, emphasizes the complexity of medication adherence. Clearly, we need a multipronged approach. As the study showed, just giving patients free assistance may not be as beneficial because, in some cases, patients may not use it. We have to look at other potential barriers and how to address them in other trials. There are a variety of different factors, and in my mind, the real challenge is if we take a horse to water, how do we get it to drink?
Perspective
Back to Top
The ARTEMIS trial was a unique trial combining health policy and cardiology. Previous trials — from the RAND health insurance experiment to the recent randomized experience of Oregon Medicaid expansion (Oregon Health Insurance Experiment) — have demonstrated that higher out-of-pocket costs for health care reduces health care utilization. Unfortunately, patients tend to reduce all health care use in response to higher costs, rather than reducing only the less beneficial or costly treatments. The ability of focused financial interventions to increase adherence to particularly beneficial therapies has not been well demonstrated.
The ARTEMIS trial studied the effect of a financial intervention to reduce and equalize the cost of ticagrelor and clopidogrel on the compliance with P2Y12 inhibitor therapy following acute MI. Ten U.S. sites were cluster randomized in a 1:2 fashion to usual care or a co-payment reduction intervention, comprised of a co-payment voucher card for either clopidogrel or ticagrelor. No other interventions were given.
After 1 year, patients with the co-payment voucher card had a lower rate of non-persistence of P2Y12 inhibitor use based on patient report (13% vs. 16%, P < .0001), pharmacy fill rates (45% vs. 54%, P < .0001) and randomly selected blood draw levels (8% vs. 12%, P = .04). There was no difference in MACE (10.2% vs. 10.6%, P = 0.65). Limitations of the study included the fact that 28% of patients in the intervention arm did not use the study voucher, either because of other insurance or because they were not planning on being adherent. In addition, the cluster randomized design gave little incentive to enroll at usual-care sites, creating an imbalance in enrollment.
The trial demonstrated that co-payment support alone has a measureable, but overall modest, effect on drug adherence, at least in the setting of post-MI care, and did not improve clinical outcomes. This may have been due to already low co-payments for branded or generic drugs for the insured population, or already strong emphasis on P2Y12 drug compliance following angioplasty. The implication as stated by the investigators is that broader financial support (i.e., insurance coverage overall) may be necessary to demonstrate improvements in health outcomes; however, the results of the Oregon Health Insurance Experiment provided no support for this theory.
A therapeutic nihilist might suggest that health care has only a minor effect on health outcomes, with larger gains to be made from interventions in public health, socioeconomic reform and prevention. More likely, in the setting of safety-net hospitals, free access to EDs and insurance for most patients, there are sufficient safeguards in even our current dysfunctional health care system to make showing a difference in clinical outcomes with cost-reduction interventions difficult.
More intriguing would be to take the opposite approach — that is, to provide financial rewards, rather than reduced costs, to encourage the use of a drug. We know that directly paying patients modest financial rewards to exercise or quit smoking is highly effective and often less costly than other interventions, so paying a patient to take their P2Y12 inhibitor might be the next step.