Contemporary use of guideline‐based higher potency P2Y12 receptor inhibitor therapy in patients with moderate‐to‐high risk non‐ST‐segment elevation myocardial infarction: Results from the Canadian ACS reflective II cross‐sectional study

Abstract Background After myocardial infarction, guidelines recommend higher‐potency P2Y12 receptor inhibitors, namely ticagrelor and prasugrel, over clopidogrel. Hypothesis We aimed to determine the contemporary use of higher‐potency antiplatelet therapy in Canadian patients with non‐ST‐elevation myocardial infarction (NSTEMI). Methods A total of 684 moderate‐to‐high risk NSTEMI patients were enrolled in the prospective Canadian ACS Reflective II registry at 12 Canadian hospitals and three clinics in five provinces between July 2016 and May 2018. Multivariable logistic regression modeling was performed to assess factors independently associated with higher‐potency P2Y12 receptor inhibitor use at discharge. Results At hospital discharge, 78.3% of patients were treated with a P2Y12 receptor inhibitor. Among patients discharged on a P2Y12 receptor inhibitor, use of higher‐potency P2Y12 receptor inhibitor was 61.4%. After adjustment, treatment in‐hospital with PCI (OR 4.48, 95%CI 3.34–6.03, p < .0001) was most strongly associated with higher use of higher‐potency P2Y12 receptor inhibitor, while oral anticoagulant use at discharge (OR 0.03, 95%CI 0.01–0.12, p < .0001), and atrial fibrillation (OR 0.40, 95%CI 0.17–0.98, p = .046) were most strongly associated with lower use of higher‐potency P2Y12 receptor inhibitor. Use of higher‐potency P2Y12 receptor inhibitor varied across provinces (range, 21.6%–78.9%). Discussion In contemporary Canadian practice, approximately 60% of moderate‐to‐high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor are treated with a higher‐potency P2Y12 receptor inhibitor. In addition to factors that increase risk of bleeding, interprovincial differences in practice patterns were associated with use of higher‐potency P2Y12 receptor inhibitor at discharge. Opportunities remain for further optimization of evidence‐based, guideline‐recommended antiplatelet therapy use.


| BACKGROUND
Dual antiplatelet therapy (DAPT) with aspirin and an oral P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent cardiovascular events after myocardial infarction (MI). The efficacy and safety of higher potency P2Y12 receptor inhibitors ticagrelor and prasugrel compared with clopidogrel were demonstrated in rigorous clinical trials, now approximately one decade ago. 1,2 As such the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the Use of Antiplatelet Therapy recommend the use of higher potency P2Y12 receptor inhibitors ticagrelor and prasugrel preferentially over clopidogrel. 3 While two Canadian observational studies of MI patients demonstrated temporal increases in P2Y12 receptor inhibitor use acutely and at discharge compared with prior national experience, 4,5 guideline-recommended use of the higher potency P2Y12 receptor inhibitors remained low, particularly among patients not undergoing PCI and in those with a diagnosis of NSTEMI. The Canadian Acute Coronary Syndrome (ACS) Reflective Program was designed to assess the appropriate use of oral antiplatelet therapies, with a primary aim to evaluate care gaps that exist between evidence-based guideline recommendations and real world practice. Here we report the contemporary in hospital and discharge use of guideline recommended higher potency P2Y12 receptor inhibitors in a moderate-to-high risk Canadian NSTEMI population, and identify opportunities where higher potency DAPT may be of potential benefit in the management of such patients.

| METHODS
The Canadian ACS Reflective II, a prospective Quality Enhancement Research Initiative (QuERI) is a knowledge translation program designed to evaluate physician decision-making and choice of guideline-recommended antiplatelet therapies in the management of NSTEMI patients. The program was conducted by the Canadian Heart Research Centre (CHRC), a not-for-profit academic research organization, with the oversight of a steering committee comprised of four Canadian cardiologists. The program objectives were: (1) to identify and describe NSTEMI patients who do not receive guidelinerecommended DAPT (ASA and P2Y12 receptor inhibitor), specifically higher potency P2Y12 receptor inhibitor, and (2)    The ACCOAST trial seeking to determine the optimal timing of prasugrel in patients with NSTEMI scheduled for coronary angiography was stopped prematurely, due to an increase in bleeding in patients with a 30 mg loading dose before angiography. 6 In contrast, the PLATO trial enrolled patients with the whole spectrum of ACS, regardless of initial invasive strategy. In addition, approximately half the patients were pretreated with clopidogrel prior to randomization.

| CONCLUSION
Approximately 60% of moderate-to-high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor in contemporary Canadian practice are treated with a higher potency P2Y12 receptor inhibitor.
In addition to factors associated with higher risk of bleeding, selection for clopidogrel at discharge was associated with not receiving PCI and interprovincial differences in practice patterns. Excluding patients with contraindications for higher potency P2Y12 receptor inhibitors and/or high bleeding risk, use of higher potency P2Y12 receptor inhibitor was still only 71.1%. Opportunities remain geographically, and among medically managed high-risk NSTEMI patients for further optimization of evidence-based, guideline-recommended antiplatelet therapy use.

ACKNOWLEDGMENTS
We thank Caroline Spindler in the administrative conduct of the study and Sue Francis for editorial assistance with the preparation of this manuscript. The ACS Reflective II was supported by the Canadian Heart Research Centre (CHRC) through an unrestricted investigatorinitiated grant from AstraZeneca Canada (Mississauga, ON, Canada).
The sponsors had no involvement in the collection, analysis, or interpretation of the data; in the writing of the report; or in the decision to submit the manuscript for publication.