Pretreatment with P2Y₁₂ inhibitors in Acute and Chronic Coronary Syndromes: for whom, when and how

In patients with acute or chronic coronary syndromes undergoing percutaneous coronary intervention, dual antiplatelet therapy-with aspirin and a P2Y₁₂ inhibitor-is the cornerstone of pharmacological treatment to prevent stent thrombosis and atherothrombotic complications. However, the timing of P2Y₁₂ inhibitor initiation has been a matter of considerable debate. Administering a P2Y₁₂ inhibitor added to aspirin before percutaneous coronary intervention without knowing coronary anatomy has the potential to ensure antithrombotic protection at percutaneous coronary intervention and to reduce procedural thrombotic complications, but also exposes patients to an increased bleeding risk, may prevent or retard surgical myocardial revascularization when needed, and may be futile or even dangerous in patients not requiring percutaneous coronary intervention. The latest 2023 European Society of Cardiology guidelines have downgraded previous recommendations to pretreatment also in ST-elevation myocardial infarction. The present Systematic Review and Consensus Document aims at reviewing clinical evidence on pretreatment across various clinical scenarios, proposing a nuanced approach that considers clinical presentation, time to treatment, the clinical setting and the probability of non-thrombotic primary causes.