Roxana Mehran1, Usman Baber1, Samin K Sharma1, David J Cohen1, Dominick J Angiolillo1, Carlo Briguori1, Jin Y Cha1, Timothy Collier1, George Dangas1, Dariusz Dudek1, Vladimír Džavík1, Javier Escaned1, Robert Gil1, Paul Gurbel1, Christian W Hamm1, Timothy Henry1, Kurt Huber1, Adnan Kastrati1, Upendra Kaul1, Ran Kornowski1, Mitchell Krucoff1, Vijay Kunadian1, Steven O Marx1, Shamir R Mehta1, David Moliterno1, E Magnus Ohman1, Keith Oldroyd1, Gennaro Sardella1, Samantha Sartori1, Richard Shlofmitz1, P Gabriel Steg1, Giora Weisz1, Bernhard Witzenbichler1, Ya-Ling Han1, Stuart Pocock1, C Michael Gibson1. 1. From the Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital (R.M., U.B., J.Y.C., G.D., S.S.), Mount Sinai Health System (S.K.S.), Columbia University Medical Center (S.O.M.), Icahn School of Medicine at Mount Sinai (S.S.), and Montefiore Medical Center (G.W.), New York, and St. Francis Hospital, Roslyn (R.S.) - all in New York; Kansas City, Missouri (D.J.C.); the University of Florida-Shands, Jacksonville (D.J.A.); Clinica Mediterranea, Naples (C.B.), and Policlinico Umberto I University, Rome (G.S.) - both in Italy; the London School of Hygiene and Tropical Medicine, London (T.C., S.P.), Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, and Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne (V.K.), and the West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow (K.O.) - all in the United Kingdom; the 2nd Department of Cardiology Jagiellonian University Medical College, Krakow (D.D.), and the Department of Invasive Cardiology, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw (R.G.) - both in Poland; Research and Innovation in Interventional Cardiology and Cardiac Intensive Care, Peter Munk Cardiac Centre, University Health Network, Toronto (V.D.), and Hamilton Health Sciences, Hamilton, ON (S.R.M.) - both in Canada; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos and Complutense University, Madrid (J.E.); Sinai Hospital of Baltimore System, Baltimore (P.G.); Kerckhoff Clinic, Bad Nauheim (C.W.H.), Deutsches Herzzentrum München, Munich (A.K.), and Helios Amper-Klinikum, Dachau (B.W.) - all in Germany; the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital, Cincinnati (T.H.); Wilhelminenhospital, Vienna (K.H.); Batra Hospital and Medical Research Centre, New Delhi, India (U.K.); Rabin Medical Center, Petach Tikva, Israel (R.K.); Duke University Medical Center-Duke Clinical Research Institute, Durham, NC (M.K., E.M.O.); the University of Kentucky, Lexington (D.M.); Groupe Hospitalier Bichat-Claude-Bernard, Paris (P.G.S.); Shenyang North Hospital, Shenyang, China (Y.H.); and Beth Israel Deaconess Medical Center, Boston (C.M.G.).
Abstract
BACKGROUND:Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to taketicagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS:We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).
RCT Entities:
BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).
Authors: Jacek Kubica; Piotr Adamski; Piotr Niezgoda; Aldona Kubica; Przemysław Podhajski; Malwina Barańska; Julia M Umińska; Łukasz Pietrzykowski; Małgorzata Ostrowska; Jolanta M Siller-Matula; Jolita Badarienė; Stanisław Bartuś; Andrzej Budaj; Sławomir Dobrzycki; Łukasz Fidor; Mariusz Gąsior; Jacek Gessek; Marek Gierlotka; Robert Gil; Jarosław Gorący; Paweł Grzelakowski; Tomasz Hajdukiewicz; Miłosz Jaguszewski; Marianna Janion; Jarosław Kasprzak; Adam Kern; Artur Klecha; Andrzej Kleinrok; Wacław Kochman; Bartosz Krakowiak; Jacek Legutko; Maciej Lesiak; Marcin Nosal; Grzegorz Piotrowski; Andrzej Przybylski; Tomasz Roleder; Grzegorz Skonieczny; Grzegorz Sobieszek; Agnieszka Tycińska; Dariusz Wojciechowski; Wojciech Wojakowski; Jarosław Wójcik; Marzenna Zielińska; Aleksander Żurakowski; Giuseppe Specchia; Diana A Gorog; Eliano P Navarese Journal: Cardiol J Date: 2021-06-07 Impact factor: 2.737
Authors: Safi U Khan; Mohammed Osman; Muhammad U Khan; Muhammad Shahzeb Khan; Di Zhao; Mamas A Mamas; Nazir Savji; Ahmad Al-Abdouh; Rani K Hasan; Erin D Michos Journal: Ann Intern Med Date: 2020-03-17 Impact factor: 25.391
Authors: Safi U Khan; Muhammad Zia Khan; Muhammad Shahzeb Khan; Ahmed Mahmood; Ankur Kalra; Edo Kaluski; Erin D Michos; Mohamad Alkhouli Journal: Eur Heart J Cardiovasc Pharmacother Date: 2021-05-23