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Lawton et al 2021 ACC/AHA/SCAI Coronary Revascularization Guideline

Circulation. 2022;145:e18–e114. DOI: 10.1161/CIR.0000000000001038 January 18, 2022 e59 CLINICAL STATEMENTS AND GUIDELINES

Observational data and retrospective analyses of RCTs have demonstrated that a lower dose of chronic daily aspirin (<100 mg) after PCI results in the best combination of safety and efficacy.24-26 On the basis of an analysis of aspirin dosing and outcomes in the PLATO (Trial to Assess The Study of Platelet Inhibition and Patient Outcomes) study, a low dose of aspirin (<100 mg) should be used in patients treated with ticagrelor. There are data to suggest that in the treatment of ACS, a chewable aspirin formulation may be preferable to solid tablet aspirin.27 2.	 P2Y12 inhibitors are essential for treating patients undergoing PCI. Their use was first evaluated in studies exploring the optimal antithrombotic regimens after coronary stent implantation. In these earlier studies, ticlopidine was found to be superior to aspirin alone or the combination of aspirin and anticoagulant therapy10,11,13 in reducing ischemic events after coronary stent implantation. Because of unacceptable side effects of ticlopidine, clopidogrel was later used in place of ticlopidine, with clinical trials demonstrating similar efficacy but lower rates of drug discontinuation attributable to noncardiac events.16 With clopidogrel, the introduction of prasugrel and ticagrelor supported the use of a more potent P2Y12 inhibitor agent for PCI in ACS.6,14 A loading dose of a P2Y12 agent should be given to minimize the time to platelet inhibition. There are conflicting data on the benefits of pretreatment with a P2Y12 inhibitor before the anatomy is known, particularly in patients with NSTE-ACS.7,17,28-31 In contemporary times, with most patients with ACS undergoing early angiography, a strategy of loading with a P2Y12 inhibitor after the anatomy is known appears to offer similar benefit to preloading.31 3.	 The CREDO (Clopidogrel for the Reduction of Events During Observation) trial18 demonstrated a reduction in ischemic events, including the risk of death, MI, or stroke, with a loading dose of clopidogrel and treatment up to 9 months after elective PCI. There was a trend toward a lower event rate when preloading with a 300-mg clopidogrel dose was given >3 hours before PCI. A 600-mg loading dose of clopidogrel is associated with a shorter time to platelet inhibition and therefore is the preferred dose. Ticagrelor and prasugrel have not been studied for long-term clinical outcomes in patients with SIHD undergoing PCI. 4.	 Patients with STEMI who were treated with fibrinolytic therapy and referred for PCI are at increased bleeding and ischemic risk. Clopidogrel is the only P2Y12 inhibitor agent studied in patients immediately after the administration of fibrinolytic therapy. In the CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) trial, clopidogrel pretreatment in conjunction with fibrinolytic therapy resulted in a 46% reduction in the rate of cardiovascular death or recurrent MI or stroke at 30 days among patients referred for PCI.5 Major and minor bleeding was similar between the groups. In this study, patients randomized to clopidogrel were administered a 300-mg load during or immediately after fibrinolytic therapy, followed by 75 mg daily.5 In contemporary times, the loading dose of clopidogrel for patients undergoing PCI after fibrinolytic therapy should be individualized. A larger loading dose of 600 mg may be used for most patients, whereas the lower 300-mg loading dose is generally reserved for older patients or those at higher risk of bleeding. 5.	 TRITON-TIMI-38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction)6 and PLATO14 demonstrated that treatment with prasugrel (TRITON-TIMI-38) and ticagrelor (PLATO), compared with clopidogrel, reduced the rate of the composite endpoint of death from vascular causes, MI, or stroke. These agents were also associated with a lower rate of stent thrombosis. In the TRITON-TIMI 38 trial, non-CABG major bleeding was significantly higher with prasugrel.6 In PLATO, although there were no significant differences in the rates of studydefined bleeding events with ticagrelor, non-CABG major bleeding was significantly higher among patients treated with ticagrelor14 than among patients treated with clopidogrel.14 Because of the increased bleeding risk, these more potent agents should be used with caution in older patients. One study suggested that clopidogrel may be a reasonable alternative for older patients with ACS undergoing PCI, with similar rates of ischemic events and less bleeding.32 The open-labeled design of this trial and the high rate of crossover limit the generalization of the study results. Further studies are needed to determine the ideal P2Y12 inhibitor for use in older patients with ACS undergoing PCI. 6.	 In patients with fibrinolytic-treated STEMI, ticagrelor is associated with a greater inhibition of platelet reactivity than that seen with clopidogrel.33 In PLATO, patients were excluded from enrollment if they were treated with fibrinolytic therapy within 24 hours of enrollment. Therefore, although PLATO supported the use of ticagrelor over clopidogrel in patients with STEMI treated with fibrinolytic therapy, there were limited data on the safety of ticagrelor when given early after fibrinolytic therapy. The TREAT (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis) trial was designed

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