P3669Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: the TROPICAL-ACS smoking substudy

Abstract

Background: A guided de‐escalation of dual antiplatelet treatment (DAPT) with an early switch from prasugrel to clopidogrel was recently identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Of note, differences in antiplatelet drug response in smokers and non‐smokers were reported in prior studies and clinical outcomes of ACS patients undergoing PCI depend on smoking status. Thus, the safety and efficacy of any DAPT de‐escalation strategy may differ in relation to smoking status. Purpose: This post‐hoc analysis of the TROPICAL‐ACS trial aimed to assess the impact of smoking on clinical outcomes following guided de‐escalation of DAPT in ACS patients. Methods: The multicentre TROPICAL‐ACS trial randomised 2610 biomarkerpositive ACS patients 1:1 to either standard treatment with prasugrel for 12 months (control group) or a platelet function testing (PFT) guided de‐escalation of DAPT. For this post‐hoc analysis, we used univariate and multivariate Cox proportional hazards models to assess the association and interaction of smoking status on clinical endpoints across study groups. Results: 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 BARC criteria) compared to control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50‐ 0.99, p=0.048). Current smokers (n=1182) showed similar event rates between study groups (6.6% vs. 6.6%; HR 1,95% CI 0.64‐1.56, p>0.99; see Figure). Of note, outcomes in non‐smokers for guided de‐escalation vs. control group patients were mainly driven by a reduction in bleeding events (BARC ≥ grade 2) (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45‐1.03, p=0.066). A Cox proportional hazards model revealed no significant interaction of smoking status with treatment effects of guided DAPT de‐escalation (p value for interaction=0.23). (Figure presented) Conclusion: Guided de‐escalation of DAPT appears to be equally safe and effective in smokers and non‐smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year potent platelet inhibition this DAPT strategy may be used as an alternative antiplatelet treatment regimen.