Last updated on November 2017

ARTEMIS D5130R00030: Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study

Brief description of study

ARTEMIS D5130R00030: Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study

Detailed Study Description

1. Background

1.1. Antiplatelet therapy after acute myocardial infarction

Dual antiplatelet therapy with aspirin, combined with a P2Y12 receptor inhibitor, is a cornerstone of therapy for acute myocardial infarction (AMI). Treatment with clopidogrel in addition to aspirin resulted in a 20% reduction in major adverse cardiovascular events (MACE) when compared with aspirin alone among all patients with non–ST-elevation acute coronary syndrome, regardless of revascularization strategy [1, 2]. The Clopidogrel as Adjunctive Reperfusion Therapy – Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial and the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) extended these results to patients with ST-segment elevation myocardial infarction (STEMI) [3, 4]. More potent inhibition of the P2Y12 receptor has led to a further reduction in clinical events. In the Study of Platelet Inhibition and Patient Outcomes (PLATO) trial, patients receiving ticagrelor had a 16% lower risk of the composite endpoint of cardiovascular death, AMI, and stroke compared with clopidogrel-treated patients [5]. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) study also demonstrated similar lowering of cardiovascular events with prasugrel compared to clopidogrel in AMI patients undergoing percutaneous coronary intervention (PCI) [6], but had no significant benefit among non-revascularized patients [7]. Compared with clopidogrel, the use of ticagrelor and prasugrel, which are both higher potency P2Y12 receptor inhibitors, has resulted in a greater risk of bleeding.

Current guidelines for the management of STEMI [8] and non-STEMI (NSTEMI) [9] recommend treatment with a P2Y12 receptor inhibitor for up to one-year post-AMI. Despite these recommendations, only 74% of AMI patients are currently prescribed a P2Y12 receptor inhibitor at discharge [10]. Rates of P2Y12 receptor inhibitor use are higher among patients treated with PCI [11], but rates are only approximately 50% for medically treated patients [12, 13]. Prasugrel and ticagrelor received regulatory approval in 2009 and 2011, respectively, and clopidogrel became available in generic formulation in 2012. Current guidelines recommend any of these three medications as first-line agents for PCI-treated AMI patients, and either clopidogrel or ticagrelor for AMI patients treated with a non-invasive strategy. Recent observational data revealed that clopidogrel is the most commonly prescribed P2Y12 receptor inhibitor [14]. Yet long-term adherence to cardiovascular medications, including P2Y12 receptor inhibitor therapy, is suboptimal [15-17], and disruption of planned antiplatelet therapy has been associated with worse clinical outcomes [16, 18, 19].

1.2. Cost sharing, clinician choice of antiplatelet agent, and long-term medication adherence Most health plans have cost-sharing strategies with tiered copayment plans that apply different patient copayment amounts for medication brands that are generic, preferred, and non-preferred. The purpose of these cost-sharing strategies is to provide incentives to use generic or lower-cost medications. In observational studies, increased out-of-pocket medication expenses have been associated with lower rates of treatment, delays to treatment, lower medication adherence, and higher drug discontinuation rates [20-24]. Lower income and older patients are at greater risk of cost-related medication nonadherence [25, 26]. Health plan changes that moved brand medications to a lower copay tier have been associated with improved adherence [27]. Therefore, copayment reduction is a potential strategy to improve medication adherence and address disparities in cardiovascular outcomes.

The Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) study randomized post-AMI patients to either usual prescription coverage or full coverage for all prescription costs. Rates of adherence to secondary prevention therapies were 4–6% higher among the full coverage group [28]. There was no significant difference in clinical outcomes for the full study population, but non-white patients had a lower incidence of vascular events and revascularization when provided with full medication coverage [29]. Nevertheless, the incentive being tested was imperfect, since the drugs that were evaluated may have already been associated with low copayments and there was a median delay of 49 days post-discharge before drug coverage began (therefore, missing the time period when many patients self-discontinue medications).

Most clinicians do not prescribe exclusively generic or branded medication for common cardiovascular classes such as statins, beta-blockers, and angiotensin-converting enzyme inhibitors [30]. Perceived medication cost to the patient may influence clinician choice of P2Y12 receptor inhibitor during hospitalization for AMI. Switching from a one-tier to a three-tiered copay system leads to increased utilization of medications with the lowest copay [31, 32], presumably due to patient and/or clinician preference to utilize the drug with the lowest out of pocket expenditure. What is unclear is whether or not the cost burden to the patient, as perceived by the clinician, influences the choice of the antiplatelet agent prescribed. Whether or not greater patient affordability will lead to improved antiplatelet therapy adherence and improved cardiovascular outcomes is also unknown.

Clinical Study Identifier: TX8478

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Jenny Martin

Baptist Health Clinical Research Center & Lexington Cardiac Research Foundation
Lexington, KY USA