Hironori Hara1, Kuniaki Takahashi1, Norihiro Kogame1, Mariusz Tomaniak2,3, Laura S M Kerkmeijer1, Masafumi Ono1, Hideyuki Kawashima1, Rutao Wang4, Chao Gao4, Joanna J Wykrzykowska1, Robbert J de Winter1, Franz-Josef Neumann5, Sylvain Plante6, Pedro Alves Lemos Neto7, Scot Garg8, Peter Jüni9, Pascal Vranckx10, Stephan Windecker11, Marco Valgimigli11, Christian Hamm12, Philippe Gabriel Steg13, Yoshinobu Onuma14, Patrick W Serruys14,15. 1. Department of Cardiology, Academic Medical Center, University of Amsterdam, the Netherlands (H.H., K.T., N.K., L.S.M.K., M.O., H.K. J.J.W., R.J.d.W.). 2. Department of Cardiology, Erasmus Medical Center, Erasmus University, Rotterdam, the Netherlands (M.T.). 3. First Department of Cardiology, Medical University of Warsaw, Poland (M.T.). 4. Department of Cardiology, Radboud University, Nijmegen, the Netherlands (R.W., C.G.). 5. Division of Cardiology and Angiology II, University Heart Center Freiburg, Bad Krozingen, Germany (F.-J.N.). 6. Division of Cardiology, Department of Medicine, Southlake Regional Health Center, Newmarket, ON, Canada (S.P.). 7. Heart Institute (InCor), University of Sao Paulo Medical School, Brazil (P.A.L.N.). 8. Department of Cardiology, Royal Blackburn Hospital, Blackburn, United Kingdom (S.G.). 9. Applied Health Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Canada (P.J.). 10. Department of Cardiology and Critical Care, Jessa Ziekenhuis Hasselt, Faculty of Medicine and Life Sciences, University of Hasselt, Belgium (P.V.). 11. Department of Cardiology, Bern University Hospital, Switzerland (S.W., M.V.). 12. Department of Cardiology, Kerckhoff Heart Center, Campus University of Giessen, Bad Nauheim, Germany (C.H.). 13. FACT, Université Paris Diderot, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France (P.G.S.). 14. Department of Cardiology, National University of Ireland, Galway (NUIG), Ireland (Y.O., P.W.S.). 15. NHLI, Imperial College London, United Kingdom (P.W.S.).
Abstract
BACKGROUND:Bleeding and myocardial infarction (MI) after percutaneous coronary intervention are independent risk factors for mortality. This study aimed to investigate the association of all-cause mortality after percutaneous coronary intervention with site-reported bleeding and MI, when considered as individual, repeated, or combined events. METHODS: We used the data from the GLOBAL LEADERS trial (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-Platelet Therapy After Stent Implantation), an all-comers trial of 15 968 patients undergoing percutaneous coronary intervention. Bleeding was defined as Bleeding Academic Research Consortium (BARC) 2, 3, or 5, whereas MI included periprocedural and spontaneous MIs according to the Third Universal Definition. RESULTS: At 2-year follow-up, 1061 and 498 patients (6.64% and 3.12%) experienced bleeding and MI, respectively. Patients with a bleeding event had a 10.8% mortality (hazard ratio [HR], 5.97 [95% CI, 4.76-7.49]; P<0.001), and the mortality of patients with an MI was 10.4% (HR, 5.06 [95% CI, 3.72-6.90]; P<0.001), whereas the overall mortality was 2.99%. Albeit reduced over time, MI and even minor BARC 2 bleeding significantly influenced mortality beyond 1 year after adverse events (HR of MI, 2.32 [95% CI, 1.18-4.55]; P=0.014, and HR of BARC 2 bleeding, 1.79 [95% CI, 1.02-3.15]; P=0.044). The mortality rates in patients with repetitive bleeding, repetitive MI, and both bleeding and MI were 16.1%, 19.2%, and 19.0%, and their HRs for 2-year mortality were 8.58 (95% CI, 5.63-13.09; P<0.001), 5.57 (95% CI, 2.53-12.25; P<0.001), and 6.60 (95% CI, 3.44-12.65; P<0.001), respectively. De-escalation of antiplatelet therapy at the time of BARC 3 bleeding was associated with a lower subsequent bleeding or MI rate, compared with continuation of antiplatelet therapy (HR, 0.32 [95% CI, 0.11-0.92]; P=0.034). CONCLUSIONS: The fatal impact of bleeding and MI persisted beyond one year. Additional bleeding or MIs resulted in a poorer prognosis. De-escalation of antiplatelet therapy at the time of BARC 3 bleeding could have a major safety merit. These results emphasize the importance of considering the net clinical benefit including ischemic and bleeding events. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01813435.
RCT Entities:
BACKGROUND:Bleeding and myocardial infarction (MI) after percutaneous coronary intervention are independent risk factors for mortality. This study aimed to investigate the association of all-cause mortality after percutaneous coronary intervention with site-reported bleeding and MI, when considered as individual, repeated, or combined events. METHODS: We used the data from the GLOBAL LEADERS trial (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-Platelet Therapy After Stent Implantation), an all-comers trial of 15 968 patients undergoing percutaneous coronary intervention. Bleeding was defined as Bleeding Academic Research Consortium (BARC) 2, 3, or 5, whereas MI included periprocedural and spontaneous MIs according to the Third Universal Definition. RESULTS: At 2-year follow-up, 1061 and 498 patients (6.64% and 3.12%) experienced bleeding and MI, respectively. Patients with a bleeding event had a 10.8% mortality (hazard ratio [HR], 5.97 [95% CI, 4.76-7.49]; P<0.001), and the mortality of patients with an MI was 10.4% (HR, 5.06 [95% CI, 3.72-6.90]; P<0.001), whereas the overall mortality was 2.99%. Albeit reduced over time, MI and even minor BARC 2 bleeding significantly influenced mortality beyond 1 year after adverse events (HR of MI, 2.32 [95% CI, 1.18-4.55]; P=0.014, and HR of BARC 2 bleeding, 1.79 [95% CI, 1.02-3.15]; P=0.044). The mortality rates in patients with repetitive bleeding, repetitive MI, and both bleeding and MI were 16.1%, 19.2%, and 19.0%, and their HRs for 2-year mortality were 8.58 (95% CI, 5.63-13.09; P<0.001), 5.57 (95% CI, 2.53-12.25; P<0.001), and 6.60 (95% CI, 3.44-12.65; P<0.001), respectively. De-escalation of antiplatelet therapy at the time of BARC 3 bleeding was associated with a lower subsequent bleeding or MI rate, compared with continuation of antiplatelet therapy (HR, 0.32 [95% CI, 0.11-0.92]; P=0.034). CONCLUSIONS: The fatal impact of bleeding and MI persisted beyond one year. Additional bleeding or MIs resulted in a poorer prognosis. De-escalation of antiplatelet therapy at the time of BARC 3 bleeding could have a major safety merit. These results emphasize the importance of considering the net clinical benefit including ischemic and bleeding events. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01813435.