Dirk Sibbing1,2, Lisa Gross1, Dietmar Trenk3, Claudius Jacobshagen4, Tobias Geisler5, Martin Hadamitzky6, Béla Merkely7, Róbert Gábor Kiss8, András Komócsi9, Radoslaw Parma10, Stephan B Felix11,12, Franz-Josef Neumann3, Jörg Hausleiter1,2, Monika Baylacher1, Lukasz Koltowski13, Julinda Mehilli1,2, Kurt Huber14, Zenon Huczek13, Dániel Aradi15, Steffen Massberg1,2. 1. Department of Cardiology, LMU München, Marchioninistraße 15, Munich, Germany. 2. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. 3. Department of Cardiology and Angiology II, University Heart Centre Freiburg, Bad Krozingen, Germany. 4. Department of Cardiology und Pneumology, Heart Centre/Georg-August-University Göttingen, Göttingen, Germany. 5. Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, Tübingen, Germany. 6. Department of Radiology, Deutsches Herzzentrum München, Munich, Germany. 7. Heart and Vascular Centre, University of Semmelweis, Budapest, Hungary. 8. Department of Cardiology, Military Hospital, Budapest, Hungary. 9. Department of Interventional Cardiology, Heart Institute, University of Pécs, Pécs, Hungary. 10. 3rd Department of Cardiology, Medical University of Silesia, Katowice, Poland. 11. Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany. 12. DZHK, partner site Greifswald, Greifswald, Germany. 13. 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. 14. 3rd Medical Department, Cardiology and Intensive Care Medicine, Sigmund Freud Private University, Medical School, Wien, Austria. 15. Heart Centre Balatonfüred and Heart and Vascular Centre, Semmelweis University, Budapest, Hungary.
Abstract
Aims: Guided de-escalation of P2Y12-inhibitor treatment was recently identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention. Safety and efficacy of this strategy may differ in relation to patient's age. This pre-specified analysis of the TROPICAL-ACS trial aimed to assess the impact of age on clinical outcomes following guided de-escalation of antiplatelet treatment in ACS patients. Methods and results: Patients were randomly assigned in a 1:1 fashion to either standard treatment with prasugrel for 12 months (control group) or to a guided de-escalation regimen (1 week prasugrel followed by 1 week clopidogrel and platelet function testing guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). We used Cox regression models to assess the associations of age on clinical endpoints and interactions. In younger patients (age ≤70, n = 2240), the 1 year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke, or bleeding ≥ grade 2 according to Bleeding Academic Research Consortium criteria) was significantly lower in guided de-escalation vs. control group [5.9% vs. 8.3%; hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.51-0.96; P = 0.03, number needed to treat = 42]. In elderly patients (age >70, n = 370), the absolute risk of events was higher without significant differences between guided de-escalation vs. control group (15.5% vs. 13.6%; HR 1.17, 95% CI 0.69-2.01; P = 0.56). When the impact of age, as a continuous variable, was analysed on outcomes after guided de-escalation vs. control treatment, an increasing relative risk reduction was observed in the primary endpoint by decreasing age (Pint = 0.02), due to significant reductions in bleeding. Conclusion: Treatment effects of guided de-escalation for P2Y12 inhibitors depend on patient's age with younger patients deriving a significant net clinical benefit. Although the safety and efficacy of guided de-escalation in the elderly was similar to uniform prasugrel therapy, this should be further investigated due to the limited sample size of this group.
RCT Entities:
Aims: Guided de-escalation of P2Y12-inhibitor treatment was recently identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention. Safety and efficacy of this strategy may differ in relation to patient's age. This pre-specified analysis of the TROPICAL-ACS trial aimed to assess the impact of age on clinical outcomes following guided de-escalation of antiplatelet treatment in ACS patients. Methods and results: Patients were randomly assigned in a 1:1 fashion to either standard treatment with prasugrel for 12 months (control group) or to a guided de-escalation regimen (1 week prasugrel followed by 1 week clopidogrel and platelet function testing guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). We used Cox regression models to assess the associations of age on clinical endpoints and interactions. In younger patients (age ≤70, n = 2240), the 1 year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke, or bleeding ≥ grade 2 according to Bleeding Academic Research Consortium criteria) was significantly lower in guided de-escalation vs. control group [5.9% vs. 8.3%; hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.51-0.96; P = 0.03, number needed to treat = 42]. In elderly patients (age >70, n = 370), the absolute risk of events was higher without significant differences between guided de-escalation vs. control group (15.5% vs. 13.6%; HR 1.17, 95% CI 0.69-2.01; P = 0.56). When the impact of age, as a continuous variable, was analysed on outcomes after guided de-escalation vs. control treatment, an increasing relative risk reduction was observed in the primary endpoint by decreasing age (Pint = 0.02), due to significant reductions in bleeding. Conclusion: Treatment effects of guided de-escalation for P2Y12 inhibitors depend on patient's age with younger patients deriving a significant net clinical benefit. Although the safety and efficacy of guided de-escalation in the elderly was similar to uniform prasugrel therapy, this should be further investigated due to the limited sample size of this group.
Authors: Lukasz Koltowski; Mariusz Tomaniak; Lisa Gross; Bartosz Rymuza; Michal Kowara; Radoslaw Parma; Anna Komosa; Mariusz Klopotowski; Claudius Jacobshagen; Tommaso Gori; Daniel Aradi; Kurt Huber; Martin Hadamitzky; Steffen Massberg; Maciej Lesiak; Krzysztof J Filipiak; Adam Witkowski; Grzegorz Opolski; Zenon Huczek; Dirk Sibbing Journal: J Thromb Thrombolysis Date: 2019-04 Impact factor: 2.300
Authors: Mohammed Ahmed Akkaif; Nur Aizati Athirah Daud; Abubakar Sha'aban; Mei Li Ng; Muhamad Ali Sk Abdul Kader; Dzul Azri Mohamed Noor; Baharudin Ibrahim Journal: Molecules Date: 2021-04-01 Impact factor: 4.411