Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study

Abstract

Background Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggest that PCI related myocardial infarction (MI) and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y 12 receptor inhibitor such as ticagrelor, may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy (DAPT) by aspirin and clopidogrel in this setting. Methods ALPHEUS (Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) (NCT02617290) is an international, multicenter, randomized, parallel-group, open label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180mg or a loading dose of clopidogrel (300 or 600mg) in addition to aspirin. Patients will then receive a DAPT with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75mg once daily for 30 days. The primary ischemic endpoint is PCI-related myocardial infarction (MI type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (BARC type 3 or 5) at 48 hours (or discharge if it occurs earlier). Conclusion ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate endpoint for mortality. RCT# NCT02617290

Mitigating effect of clopidogrel and systematic management on adverse events after interventional therapy for coronary heart disease

“…Adverse cardiovascular events including thrombus, hemorrhage, reinfarction, and myocardial ischemia are common after interventional therapy in patients with coronary heart disease. It would compromise the treatment outcome, undermine the patient's prognosis, and increase the risk of sequelae [13][14][15]. Therefore, anticoagulant drugs to counteract the above-mentioned adverse events are in urgent need.…”

“…In addition, interventional treatment of coronary heart disease requires surgery to insert a stent into the patient's artery. Thus, puncture infection may occur in the course of recovery, and proper care is required to avoid puncture infection [16][17][18][19].…”

Mechanisms and Definitions of Periprocedural Myocardial Infarction in the Era of Modern Revascularization

“…Otherwise, a loading dose with ticagrelor or crushed prasugrel which onset of action starts within 30 min, with clopidogrel given subsequently (600 mg loading dose, 75 mg daily dose) may be used. The Assessment of Loading With the P2Y12 inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial randomly assigned 1910 patients undergoing elective high-risk PCI to receive either ticagrelor (180 mg loading dose, 90 mg twice daily subsequently for 30 days) or clopidogrel (300–600 mg loading dose, 75 mg daily subsequently for 30 days) [ 58 ]. High-risk PCI was defined as at least one of the following features: age 75 years, renal insufficiency, diabetes mellitus, overweight, acute coronary syndrome in the past 12 months, left ventricular ejection fraction 40% and/or prior episode of heart failure, multivessel disease, multiple stenting, left main stenting, bifurcation stenting, American College of Cardiology/American Heart Association (ACC/AHA) type B2 or C lesion, stenting of venous or arterial coronary graft.…”