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Background: Congress established the Appropriate Use Criteria (AUC) Program to reduce unnecessary advanced imaging studies. Organizations that wish to develop AUC can apply to the Centers for Medicare & Medicaid Services (CMS) to qualify as provider-led entities (PLEs) under this program. Variable methods, content, and formatting of PLE-generated AUC could lead to clinician uncertainty about whether an advanced imaging test is appropriate or not., Purpose: To review AUC published by CMS-qualified PLEs focused on advanced imaging tests for coronary artery disease (CAD), a "priority clinical area" identified by CMS., Data Sources: Publicly available data from the worldwide web searched on 29 August 2022., Study Selection: Approved AUC with recommendations related to testing for CAD., Data Extraction: Manual review of published AUC by all authors., Data Synthesis: Among the 17 CMS-qualified PLEs, only 7 had published AUC related to CAD. Substantial variation in the methods and formatting of these AUCs was observed. The number of clinical scenarios covered ranged from 6 to 210, and the number of advanced imaging methods covered ranged from 1 to 25. When specifically applied to clinical scenarios, many AUC offered no guidance on appropriateness; those that did conflicted with respect to appropriateness., Limitation: Other CMS-identified priority clinical areas were not evaluated., Conclusion: CMS-qualified AUC for imaging of CAD are heterogeneous and sometimes discrepant, creating substantial potential for uncertainty among clinicians seeking to provide their patients with appropriate imaging tests., Primary Funding Source: No funding was received for this study., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1011.

Objective: The aim of this study was to determine the impact of cangrelor and prasugrel on the pharmacodynamic effects of each agent., Background: The development of an intravenous P2Y12 antagonist necessitates transition between intravenous and oral therapy., Methods: Patients (n=15) with stable coronary artery disease who were taking 81 mg aspirin daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 60 mg dose of prasugrel at 1 h (n=3), 1.5 h (n=6), 2 h (n=3), or 2.5 h (n=3). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 μmol/l ADP, VerifyNow, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 10 mg of prasugrel daily for either 5 days (n=6) or 6 days (n=6). On study day 8, pharmacodynamic effects were assessed before and during a bolus plus 2-h infusion of cangrelor., Results: During cangrelor infusion (days 1 and 8), extensive inhibition of platelet function, reflected by limited residual platelet reactivity, was apparent. On day 1, transient (limited to the first hour after cangrelor was stopped) but substantial (>50%) recovery of platelet reactivity was observed. This recovery was attenuated when prasugrel was given at 1.5 h (30 min before cangrelor was stopped)., Conclusion: Prasugrel did not alter the antiplatelet effects of cangrelor, but transient recovery of platelet reactivity was apparent during the transition from cangrelor to prasugrel. Recovery of platelet reactivity was limited when prasugrel was administered 30 min before the end of the cangrelor infusion.

Objectives: This study sought to determine pharmacodynamic effects during transition from intravenous cangrelor to oral ticagrelor and from oral ticagrelor to intravenous cangrelor., Background: Cangrelor is an intravenous antagonist of P2Y12 and its use will require transition to and from oral agents., Methods: Patients (n = 12) with stable coronary artery disease who were taking aspirin 81 mg daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 180-mg dose of ticagrelor at either 0.5 h (n = 6) or 1.25 h (n = 6). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 and 5 μmol/l adenosine diphosphate, VerifyNow, P2Y12 assay (Accumetrics, San Diego, California), vasodilator-stimulated phosphoprotein index, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 90 mg of ticagrelor twice daily for either 6 (n = 6) or 7 (n = 6) doses. On study day 5, pharmacodynamic effects were assessed before and during a bolus plus 2-h infusion of cangrelor., Results: During cangrelor infusion, extensive inhibition of platelet function reflected by limited residual platelet reactivity was apparent. After cangrelor was stopped, the antiplatelet effects of ticagrelor were preserved despite a modest increase in platelet reactivity., Conclusions: Ticagrelor given before or during infusion of cangrelor did not attenuate the pharmacodynamic effects of cangrelor. The pharmacodynamic effects of ticagrelor were preserved when ticagrelor was given during infusion of cangrelor. Consistent with the reversible binding of ticagrelor, this oral P2Y12 antagonist can be administered before, during, or after treatment with cangrelor., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Obesity is associated with increased platelet reactivity. Greater platelet reactivity presages adverse events in patients with coronary artery disease (CAD). We investigated whether exercise training and weight loss reduce platelet reactivity in overweight subjects with CAD., Methods: Study subjects (N = 46) were enrolled in a prospective randomized study of exercise training and behavioral weight loss, which contrasted the amount of exercise performed (750 vs. >3000 kcal/week). Platelet reactivity was assessed with the use of flow cytometry as the percentage of platelets expressing P-selectin or capable of binding fibrinogen in response to 1 μM adenosine diphosphate in blood before and after a 4-month program of exercise and behavioral weight loss. Markers of inflammation (high-sensitivity C-reactive protein), procoagulant activity (tissue plasminogen activator, plasminogen activator inhibitor 1), insulin sensitivity, body composition, physical activity, and fitness were also recorded., Results: Platelet reactivity as assessed by P-selectin expression was decreased after exercise training and weight loss in study participants (from 34 ± 17% to 29 ± 17%; P = .01). The decrease was more pronounced in women (by 13% vs. 2% in men; P < .01). The change in platelet reactivity was not independently associated with measures of body composition or fitness. After controlling for exercise group and gender, the change in platelet reactivity was associated with changes in high-sensitivity C-reactive protein (r = 0.46) and insulin sensitivity (r = 0.46)., Conclusions: In overweight patients with CAD, exercise training and weight loss are associated with a decrease in platelet reactivity that may predict an improved prognosis.

Objective: To characterize effects of bivalirudin compared with unfractionated heparin plus eptifibatide on inflammation, and thrombin generation and activity after percutaneous coronary intervention., Methods: We measured the concentration in blood of fibrinopeptide A, prothrombin fragment 1+2, soluble CD40 ligand, interleukin 1 receptor antagonist, interleukin 6, and high sensitivity C-reactive protein in 63 patients treated with aspirin and clopidogrel and undergoing elective percutaneous coronary intervention, who were randomized to treatment with either bivalirudin (n=34) or unfractionated heparin plus eptifibatide (n=29)., Results: Neither generation nor activity of thrombin increased 10 min after percutaneous coronary intervention in patients randomized to bivalirudin or unfractionated heparin plus eptifibatide. However, prothrombin fragment 1+2 increased modestly and comparably in both groups after 1 day. Inflammation, reflected by concentrations of interleukin 6 and high sensitivity C-reactive protein in blood, increased similarly 1 day after percutaneous coronary intervention in patients treated with either regimen. In a subset of patients (n=12 in each group) from whom blood was obtained 30 days after percutaneous coronary intervention, the concentration of high sensitivity C-reactive protein was lower in those who had been treated with bivalirudin (by 3.5 mg/l, P=0.002)., Conclusion: The early effects on inflammation and thrombin generation and activity are similar after treatment with bivalirudin alone compared with unfractionated heparin plus eptifibatide in patients treated with aspirin and clopidogrel who are undergoing percutaneous coronary intervention for symptoms of stable angina. The decreased concentration of high sensitivity C-reactive protein seen 30 days after percutaneous coronary intervention in those treated with bivalirudin is consistent with greater attenuation of inflammation that may have contributed to the trend toward reduced mortality 1 year later in those treated with bivalirudin in REPLACE-2.