Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: a substudy from the randomized TROPICAL-ACS trial

• Published in: European heart journal. Cardiovascular pharmacotherapy 2020-11, Vol.6 (6), p.372-381
• Main Authors: Orban, Martin, Trenk, Dietmar, Geisler, Tobias, Rieber, Johannes, Hadamitzky, Martin, Gross, Lisa, Orban, Mathias, Kupka, Danny, Baylacher, Monika, Müller, Susan, Huber, Kurt, Koltowski, Lukasz, Huczek, Zenon, Heyn, Jens, Jacobshagen, Claudius, Aradi, Dániel, Massberg, Steffen, Sibbing, Dirk, Hein, Ralph
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome - blood; Acute Coronary Syndrome - mortality; Acute Coronary Syndrome - therapy; Acute coronary syndromes; Adenosine; Adenosine diphosphate; Adenosine triphosphatase; Aged; Aggregation; Analysis; Blood platelets; Cardiac patients; Care and treatment; Clinical outcomes; Clinical trials; Coronary heart disease; Drug Administration Schedule; Drug Monitoring; Drug Substitution; Drug therapy; Dual Anti-Platelet Therapy - adverse effects; Europe; Female; Hemorrhage - chemically induced; Humans; Male; Middle Aged; Non-Smokers; Patient outcomes; Percutaneous Coronary Intervention - adverse effects; Percutaneous Coronary Intervention - mortality; Pharmaceutical industry; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Function Tests; Purinergic P2Y Receptor Antagonists - administration & dosage; Purinergic P2Y Receptor Antagonists - adverse effects; Risk Assessment; Risk Factors; Smokers; Smoking; Smoking - adverse effects; Smoking - blood; Smoking - mortality; Thrombosis; Time Factors; Treatment Outcome
• ISSN: 2055-6837; 2055-6845
• DOI: 10.1093/ehjcvp/pvz084

Abstract Aims Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. Methods and results The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64–1.56, P > 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50–0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45–1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20–40)] vs. non-smoker [median 24 U (16–25), P