Ticagrelor With or Without Aspirin in High -Risk Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention

被引：74

作者：

Angiolill, Dominick J. ^{[1
]}

Baber, Usman ^{[2
]}

Sartori, Samantha ^{[2
]}

Briguori, Carlo ^{[3
]}

Dangas, George ^{[2
]}

Cohen, David J. ^{[4
]}

Mehta, Shamir R. ^{[5
,6
]}

Gibson, C. Michael ^{[7
]}

Chandiramani, Rishi ^{[2
]}

Huber, Kurt ^{[8
,9
]}

Kornowski, Ran ^{[10
]}

Weisz, Giora ^{[11
]}

Kunadian, Vijay ^{[12
,13
]}

Oldroyd, Keith G. ^{[14
]}

Han Ya-Ling ^{[15
]}

Kaul, Upendra ^{[16
]}

Witzenbichler, Bernhard ^{[17
]}

Dudek, Dariusz ^{[18
,19
]}

Sardella, Gennaro ^{[20
]}

Escaned, Javier ^{[21
]}

Sharma, Samin ^{[2
]}

Shlofmitz, Richard A. ^{[22
]}

Collier, Timothy ^{[23
]}

Pocock, Stuart ^{[23
]}

Mehran, Roxana ^{[2
]}

机构：

[1] Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA

[2] Icahn Sch Med Mt Sinai, Zena & Michael Wiener Cardiovasc Inst, New York, NY 10029 USA

[3] Mediterranea Cardioctr, Naples, Italy

[4] Univ Missouri, Kansas City, MO 64110 USA

[5] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada

[6] Hamilton Hlth Sci, Hamilton, ON, Canada

[7] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02115 USA

[8] Wilhelminen Hosp, Dept Med Cardiol & Intens Care Med 3, Vienna, Austria

[9] Sigmund Freud Univ, Fac Med, Vienna, Austria

[10] Rabin Med Ctr, Cardiol Dept, Petah Tiqwa, Israel

[11] Montefiore Med Ctr, Dept Cardiol, 111 E 210th St, Bronx, NY 10467 USA

[12] Newcastle Univ, Fac Med Sci, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England

[13] Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Newcastle Upon Tyne, Tyne & Wear, England

[14] Golden Jubilee Natl Hosp, West Scotland Heart & Lung Ctr, Glasgow, Lanark, Scotland

[15] Gen Hosp Shenyang Mil Reg, Dept Cardiol, Shenyang, Liaoning, Peoples R China

[16] Batra Hosp & Med Res Ctr, New Delhi, India

[17] Helios Amper Klinikum, Dept Cardiol & Pneumol, Dachau, Germany

[18] Jagiellonian Univ Med Coll, Inst Cardiol, Krakow, Poland

[19] Maria Cecilia Hosp, GVM Care & Res, Cotignola, RA, Italy

[20] Sapienza Univ Rome, Policlin Umberto 1, Dept Cardiol, Rome, Italy

[21] Univ Complutense Madrid, Hosp Clin San Carlos IDISSC, Madrid, Spain

[22] St Francis Hosp, Roslyn, NY USA

[23] London Sch Hyg & Trop Med, Dept Med Stat, London, England

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2020年 / 75卷 / 19期

关键词：

aspirin; bleeding; diabetes mellitus; thrombosis; ticagrelor monotherapy; DUAL ANTIPLATELET THERAPY; P2Y(12) RECEPTOR BLOCKADE; BLEEDING EVENTS; CLOPIDOGREL; RESPONSIVENESS; INHIBITION; OUTCOMES; DISEASE; TRIALS; TIMI;

D O I：

10.1016/j.jacc.2020.03.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND P2Y(12) inhibitor monotherapy with ticagrelor after a brief period of dual antiplatelet therapy can reduce bleeding without increasing ischemic harm after percutaneous coronary intervention (PCI). The impact of this approach among patients with diabetes mellitus (DM) remains unknown. OBJECTIVES The purpose of this study was to examine the effect of ticagrelor monotherapy versus ticagrelor plus aspirin among patients with DM undergoing PCI. METHODS This was a pre-specified analysis of the DM cohort in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial. After 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The primary endpoint was Bleeding Academic Research Consortium 2, 3, or 5 bleeding. The composite ischemic endpoint was all-cause death, myocardial infarction, or stroke. RESULTS Patients with DM comprised 37% (n = 2,620) of the randomized cohort and were characterized by more frequent comorbidities and a higher prevalence of multivessel disease. The incidence of Bleeding Academic Research Consortium 2, 3, or 5 bleeding was 4.5% and 6.7% among patients with DM randomized to ticagrelor plus placebo versus ticagrelor plus aspirin (hazard ratio: 0.65; 95% confidence interval: 0.47 to 0.91; p = 0.012). Ticagrelor monotherapy was not associated with an increase in ischemic events compared with ticagrelor plus aspirin (4.6% vs. 5.9%; hazard ratio: 0.77; 95% confidence interval: 0.55 to 1.09; p = 0.14). In the overall trial population, there was no significant interaction between DM status and treatment group for the primary bleeding or ischemic endpoints. CONCLUSIONS Compared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without DM undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242) (J Am Coll Cardiol 2020;75:2403-13) (c) 2020 by the American College of Cardiology Foundation.

引用

页码：2403 / 2413

页数：11

共 38 条

[1] Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment [J].

Angiolillo, DJ ;

Fernandez-Ortiz, A ;

Bernardo, E ;

Ramírez, C ;

Sabaté, M ;

Jimenez-Quevedo, P ;

Hernández, R ;

Moreno, R ;

Escaned, J ;

Alfonso, F ;

Bañuelos, C ;

Costa, MA ;

Bass, TA ;

Macaya, C .

DIABETES, 2005, 54 (08) :2430-2435

[2] Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment [J].

Angiolillo, Dominick J. ;

Bernardo, Esther ;

Ramirez, Celia ;

Costa, Marco A. ;

Sabate, Manel ;

Jimenez-Quevedo, Pilar ;

Hernandez, Rosana ;

Moreno, Raul ;

Escaned, Javier ;

Alfonso, Fernando ;

Banuelos, Camino ;

Bass, Theodore A. ;

Macaya, Carlos ;

Fernandez-Ortiz, Antonio .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 48 (02) :298-304

[3] Impaired Responsiveness to the Platelet P2Y12 Receptor Antagonist Clopidogrel in Patients With Type 2 Diabetes and Coronary Artery Disease [J].

Angiolillo, Dominick J. ;

Jakubowski, Joseph A. ;

Ferreiro, Jose Luis ;

Tello-Montoliu, Antonio ;

Rollini, Fabiana ;

Franchi, Francesco ;

Ueno, Masafumi ;

Darlington, Andrew ;

Desai, Bhaloo ;

Moser, Brian A. ;

Sugidachi, Atsuhiro ;

Guzman, Luis A. ;

Bass, Theodore A. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2014, 64 (10) :1005-1014

[4] In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation [J].

Armstrong, P. C. J. ;

Leadbeater, P. D. ;

Chan, M. V. ;

Kirkby, N. S. ;

Jakubowski, J. A. ;

Mitchell, J. A. ;

Warner, T. D. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2011, 9 (03) :552-561

[5] Ticagrelor With or Without Aspirin After PCI The TWILIGHT Platelet Substudy [J].

Baber, Usman ;

Zafar, M. Urooj ;

Dangas, George ;

Escolar, Gines ;

Angiolillo, Dominick J. ;

Sharma, Samin K. ;

Kini, Annapoorna S. ;

Sartori, Samantha ;

Joyce, Lauren ;

Vogel, Birgit ;

Farhan, Serdar ;

Gurbel, Paul ;

Gibson, C. Michael ;

Fuster, Valentin ;

Mehran, Roxana ;

Badimon, Juan J. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2020, 75 (06) :578-586

[6] Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: Rationale and design of the TWILIGHT study [J].

Baber, Usman ;

Dangas, George ;

Cohen, David J. ;

Gibson, C. Michael ;

Mehta, Shamir R. ;

Angiolillo, Dominick J. ;

Pocock, Stuart J. ;

Krucoff, Mitchell W. ;

Kastrati, Adnan ;

Ohman, E. Magnus ;

Steg, Philippe Gabriel ;

Badimon, Juan ;

Zafar, M. Urooj ;

Chandrasekhar, Jaya ;

Sartori, Samantha ;

Aquino, Melissa ;

Mehran, Roxana .

AMERICAN HEART JOURNAL, 2016, 182 :125-134

[7] Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial [J].

Bhatt, Deepak L. ;

Steg, Philippe Gabriel ;

Mehta, Shamir R. ;

Leiter, Lawrence A. ;

Simon, Tabassome ;

Fox, Kim ;

Held, Claes ;

Andersson, Marielle ;

Himmelmann, Anders ;

Ridderstrale, Wilhelm ;

Chen, Jersey ;

Song, Yang ;

Diaz, Rafael ;

Goto, Shinya ;

James, Stefan K. ;

Ray, Kausik K. ;

Parkhomenko, Alexander N. ;

Kosiborod, Mikhail N. ;

McGuire, Darren K. ;

Harrington, Robert A. .

LANCET, 2019, 394 (10204) :1169-1180

[8] Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus [J].

Bhatt, Deepak L. ;

Grosser, Tilo ;

Dong, Jing-fei ;

Logan, Douglas ;

Jeske, Walter ;

Angiolillo, Dominick J. ;

Frelinger, Andrew L., III ;

Lei, Lanyu ;

Liang, Juan ;

Moore, Jason E. ;

Cryer, Byron ;

Marathi, Upendra .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2017, 69 (06) :603-612

[9] Reduction in Ischemic Events With Ticagrelor in Diabetic Patients With Prior Myocardial Infarction in PEGASUS-TIMI 54 [J].

Bhatt, Deepak L. ;

Bonaca, Marc P. ;

Bansilal, Sameer ;

Angiolillo, Dominick J. ;

Cohen, Marc ;

Storey, Robert F. ;

Im, Kyungah ;

Murphy, Sabina A. ;

Held, Peter ;

Braunwald, Eugene ;

Sabatine, Marc S. ;

Steg, Ph. Gabriel .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2016, 67 (23) :2732-2740

[10] Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [J].

Bittl, John A. ;

Baber, Usman ;

Bradley, Steven M. ;

Wijeysundera, Duminda N. .

CIRCULATION, 2016, 134 (10) :E156-E178

← 1 2 3 4 →