Cited by 1,999Antiplatelet Therapy and Cardiovascular DiseasesAcute Myocardial Infarction ResearchCoronary Interventions and Diagnostics

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Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction

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Bonaca, Marc P., Bhatt, Deepak L., Cohen, Marc, Steg, Philippe Gabriel, Storey, Robert F., Jensen, Eva C., Magnani, Giulia, Bansilal, Sameer, Fish, M. Polly, Im, Kyungah, Bengtsson, Olof, Ophuis, Ton Oude, Budaj, Andrzej, Theroux, Pierre, Ruda, Mikhail, Hamm, Christian, Goto, Shinya, Spinar, Jindrich, Nicolau, José Carlos, Kiss, Robert G., Murphy, Sabina A., Wiviott, Stephen D., Held, Peter, Braunwald, Eugene, Sabatine, Marc S.·2015·New England Journal of Medicine

DOI 10.1056/nejmoa1500857

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Abstract

BACKGROUND: The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context. METHODS: We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. RESULTS: The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively. CONCLUSIONS: In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.).

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Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes
Alfredsson, J., Neely, B., Neely, M. L., Bhatt, D. L., Goodman, S. G., Tricoci, P., Mahaffey, K. W., Cornel, J. H., White, H. D., Fox, K. A. A., et al. (2017) · Heart · doi:10.1136/heartjnl-2016-310090 · Cited by 44
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“A higher bleeding risk in the chronic treatment phase was also found for other potent P2Y12 inhibitors in large-scale clinical trials, such as the cyclo-pentyl-triazolo-pyrimidine derivative ticagrelor (15, 16).”
BackgroundSelf-citation
Duration of dual antiplatelet therapy in acute coronary syndrome
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Self-citation
A randomised trial on the effect of anti-platelet therapy on the systemic inflammatory response in human endotoxaemia
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“A post-hoc analysis of the PLATelet inhibition and patient Outcomes (PLATO) trial suggested a reduced mortality after pulmonary infections and sepsis in patients treated with ticagrelor and ASA, compared to patients treated with clopidogrel and ASA (15), although a beneficial effect on sepsis-related mortality of tica…”
Result
TRPA1 Promotes Cardiac Myofibroblast Transdifferentiation after Myocardial Infarction Injury via the Calcineurin-NFAT-DYRK1A Signaling Pathway
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“Cardiovascular diseases remain the leading cause of mortality worldwide, with myocardial infarction- (MI-) based injury and subsequent left ventricular (LV) remodeling and heart failure as the major sequelae underlying this lethality [1].”
Background
Duration of dual antiplatelet therapy after coronary artery stenting: where is the sweet spot between ischaemia and bleeding?
Binder, R. K., & Lüscher, T. F. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv103 · Cited by 42
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Coppens, M., Weitz, J. I., & Eikelboom, J. W. (2019) · Circulation Research · doi:10.1161/circresaha.118.313141 · Cited by 42
Clinical Application of High-Sensitivity Troponin Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol Guidelines
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Self-citation
Patient-tailored antithrombotic therapy following percutaneous coronary intervention
van der Sangen, N. M. R., Rozemeijer, R., Yin, D. R. P. P. C. P., Valgimigli, M., Windecker, S., James, S. K., Buccheri, S., ten Berg, J. M., Henriques, J. P. S., Voskuil, M., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa1097 · Cited by 42
“24 The absolute decrease in the primary efficacy endpoint was similar in magnitude to the increase in the primary bleeding endpoint indicating no clear benefit for the study population as a whole.”
Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology 2023 Focused Update of the Guidelines for the Use of Antiplatelet Therapy
Bainey, K. R., Marquis‐Gravel, G., Belley‐Côté, E. P., Turgeon, R. D., Ackman, M. L., Babadagli, H. E., Bewick, D. J., Boivin‐Proulx, L., Cantor, W. J., Fremes, S. E., et al. (2023) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2023.10.013 · Cited by 46
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Secondary prevention after coronary artery bypass graft surgery
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“Most recently, in Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54, a long-term prevention study, patients with CAD and a previous MI had a significantly lower risk of adverse cardiovascular…”
Background
Systematic detection of polyvascular disease combined with aggressive secondary prevention in patients presenting with severe coronary artery disease: The randomized AMERICA Study
Collet, J., Cayla, G., Ennezat, P., Leclercq, F., Cuisset, T., Elhadad, S., Henry, P., Belle, L., Cohen, A. A., Silvain, J., et al. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.11.081 · Cited by 41
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Antithrombotic therapy and major adverse limb events in patients with chronic lower extremity arterial disease: systematic review and meta-analysis from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy in Collaboration with the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases
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Self-citation
Role of diabetes in stroke: Recent advances in pathophysiology and clinical management
Bradley, S., Spring, K. J., Beran, R. G., Chatzis, D., Killingsworth, M. C., & Bhaskar, S. M. M. (2021) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3495 · Cited by 42
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“21 000 stable patients were randomized 1–3 years after an initial myocardial infarction to ticagrelor 60 or 90 mg twice daily or placebo on a background of low-dose aspirin.(25) Both ticagrelor doses reduced, vs.”
Incidence and Causes for Early Ticagrelor Discontinuation: A “Real-World” Dutch Registry Experience
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Rivaroxaban: A New Treatment Paradigm in the Setting of Vascular Protection?
Zannad, F. M., & Bauersachs, R. M. (2018) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1636530 · Cited by 44
Progress in the development of antiplatelet agents: Focus on the targeted molecular pathway from bench to clinic
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Bleeding after antiplatelet therapy for the treatment of acute coronary syndromes: a review of the evidence and evolving paradigms
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“The long-term safety and efficacy of ticagrelor use for secondary cardiovascular prevention after MI has been investigated in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin (PEGASUS)-TIMI 54 trial [69].”
BackgroundMethod
Stratified Approaches to Antiplatelet Therapies Based on Platelet Reactivity Testing
Ostrowska, M., Kubica, J., Adamski, P., Kubica, A., Eyileten, C., Postula, M. A., Toma, A., Hengstenberg, C., & Siller-Matula, J. M. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00176 · Cited by 40
Ticagrelor: clinical development and future potential
Sanderson, N. C., Parker, W. A., & Storey, R. F. (2021) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2202044 · Cited by 40
“54 (2015) [13] 21,162 patients with prior spontaneous”
BackgroundSelf-citation
Contemporary Management of Stable Coronary Artery Disease
Bertolone, D. T., Gallinoro, E., Esposito, G., Paolisso, P., Bermpeis, K., Colle, C. D., Fabbricatore, D., Mileva, N. B., Valeriano, C., Munhoz, D., et al. (2022) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-021-00497-z · Cited by 45
“However, the lower ticagrelor dose of 60 mg appeared to be better tolerated, such that it preserved the efficacy in ischemic events without an excess in major bleeding complications as the 90 mg dose [91].”
Background
Platelet–Neutrophil Interaction and Thromboinflammation in Diabetes: Considerations for Novel Therapeutic Approaches
Gauer, J. S., Ajjan, R., & Ariëns, R. A. S. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.027071 · Cited by 40
Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients With Previous Myocardial Infarction and No History of Stroke or Transient Ischemic Attack
Bohula, E. A., Aylward, P. E., Bonaca, M. P., Corbalan, R. L., Kiss, R. G., Murphy, S. A., Scirica, B. M., White, H. D., D, E. B. M., & Morrow, D. A. (2015) · Circulation · doi:10.1161/circulationaha.114.015042 · Cited by 38
“Additionally, in the PEGASUS-TIMI 54 Trial, extended P2Y12 inhibition with the addition of ticagrelor to aspirin reduced major cardiovascular events in patients with an MI within 1-3 years of enrollment.(10) In both of these trials, the atherothrombotic benefits came at the cost of increased bleeding.”
BackgroundMethodSelf-citation
Pharmacodynamic Effects of Switching From Prasugrel to Ticagrelor
Franchi, F., Faz, G. T., Rollini, F., Park, Y., Cho, J. R., Thano, E., Hu, J., Kureti, M., Aggarwal, N. R., Durairaj, A., et al. (2016) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2016.02.039 · Cited by 38
“The recent demonstration of ischemic benefits, albeit at the expense of increased bleeding, associated with prolonging ticagrelor therapy beyond 1 year post-ACS may also be a reason to switch from prasugrel to ticagrelor (14).”
Background
Cangrelor
Sible, A. M., & Nawarskas, J. J. (2017) · Cardiology in Review · doi:10.1097/crd.0000000000000142 · Cited by 39
Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry
Abtan, J., Bhatt, D. L., Elbez, Y., Sorbets, E., Eagle, K. A., Reid, C. M., Baumgärtner, I., Wu, D., Hanson, M. E., Hannachi, H., et al. (2017) · Clinical Cardiology · doi:10.1002/clc.22721 · Cited by 40
“A subgroup analysis of the PLATO (Study of PLATelet inhibition and patient Outcomes) trial showed that the benefit of ticagrelor over clopidogrel in acute coronary syndrome patients was consistent in the subgroup of PAD patients compared with the global population.36 A similar analysis from the post-MI PEGASUS (PEGASU…”
MethodInfluentialSelf-citation
Planning secondary prevention: Room for improvement
Beringola, A. C., Fitzsimons, D., Pelliccia, A., Moreno, G., Martín‐Asenjo, R., & Bueno, H. (2017) · European Journal of Preventive Cardiology · doi:10.1177/2047487317704954 · Cited by 38
Frequency, Predictors, and Impact of Combined Antiplatelet Therapy on Venous Thromboembolism in Patients With Symptomatic Atherosclerosis
Cavallari, I., Morrow, D. A., Creager, M. A., Olin, J. W., Bhatt, D. L., Steg, P. G., Storey, R. F., Cohen, M. C., Scirica, B. S., Piazza, G., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.031062 · Cited by 39
Self-citation
Temporal Trends in Utilization of Cardiac Therapies and Outcomes for Myocardial Infarction by Degree of Chronic Kidney Disease: A Report From the NCDR Chest Pain–MI Registry
Bagai, A., Lu, D., Lucas, J., Goyal, A., Herzog, C. A., Wang, T. Y., Goodman, S. G., & Roe, M. T. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.010394 · Cited by 38
Btk Inhibitors as First Oral Atherothrombosis-Selective Antiplatelet Drugs?
Busygina, K., Denzinger, V., Bernlochner, I., Weber, C., Lorenz, R. L., & Siess, W. (2019) · Thrombosis and Haemostasis · doi:10.1055/s-0039-1687877 · Cited by 38
Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54
Furtado, R. H. M., Nicolau, J. C., Magnani, G., Im, K., Bhatt, D. L., Storey, R. F., Steg, P. G., Špinar, J., Budaj, A., Kontny, F. P., et al. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz821 · Cited by 38
Self-citation
Management of stable angina: A commentary on the European Society of Cardiology guidelines
Ambrosio, G., Mugelli, A., Lopez-Sendon, J. L., Tamargo, J. L., & Camm, A. J. (2016) · European Journal of Preventive Cardiology · doi:10.1177/2047487316648475 · Cited by 38
Comparison of Unguided De-Escalation Versus Guided Selection of Dual Antiplatelet Therapy After Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis
Kuno, T., Fujisaki, T., Shoji, S., Sahashi, Y., Tsugawa, Y., Iwagami, M., Takagi, H., Briasoulis, Α., Deharo, P., Cuisset, T., et al. (2022) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.122.011990 · Cited by 37
Self-citation
Antiplatelet therapy in acute coronary syndromes
Grove, E. L., Würtz, M., Thomas, M. R., & Kristensen, S. D. (2015) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2015.1079619 · Cited by 38
“As discussed in detail above, the PEGASUS trial recently investigated the potential benefit of DAPT with aspirin and ticagrelor beyond 1 year in patients with MI [47].”
BackgroundMethod
Occurrence, causes, and outcome after switching from ticagrelor to clopidogrel in a real-life scenario: data from a prospective registry
Biscaglia, S., Campo, G. C., Pavasini, R., Tebaldi, M., Tumscitz, C., & Ferrari, R. (2016) · Platelets · doi:10.3109/09537104.2015.1119815 · Cited by 37
“Nevertheless, our study population well reflects the daily clinical practice, our protocol is consistent with available data [2, 4, 10], and no other strategy has been prospectively validated.”
Result
Consensus Document ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: Long-term Antiplatelet Therapy in Patients with Coronary Artery Disease
Gulizia, M. M., Colivicchi, F., Abrignani, M. G., Ambrosetti, M., Aspromonte, N., Barile, G., Caporale, R., Casolo, G., Chiuini, E., Lenarda, A. D., et al. (2018) · European Heart Journal Supplements · doi:10.1093/eurheartj/suy019 · Cited by 38
Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry
D’Ascenzo, F., Bertaina, M., Fioravanti, F., Bongiovanni, F., Raposeiras‐Roubín, S., Abu‐Assi, E., Kinnaird, T. D., Ariza‐Solé, A., Manzano‐Fernández, S., Templin, C., et al. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319836327 · Cited by 37
“In particular, Bonaca et al.(25) recently demonstrated that extending DAPT with ticagrelor beyond 12 months led to a reduction of ischaemic events in patients with recent acute myocardial infarction and high ischaemic risk profile.”
BackgroundInfluentialSelf-citation
Antithrombotics
Verheugt, F. W. A., ten Berg, J. M., Storey, R. F., Cuisset, T., & Granger, C. B. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.02.080 · Cited by 40
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Management of Bleeding Events Associated with Antiplatelet Therapy: Evidence, Uncertainties and Pitfalls
Godiér, A., Albaladejo, P., & the French Working Group on Perioperative Haemostasis (GIHP) Group (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9072318 · Cited by 37
Mechanistic Insights to Target Atherosclerosis Residual Risk
Alkhalil, M. (2019) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2019.06.004 · Cited by 38
Long-term use of dual antiplatelet therapy for the secondary prevention of atherothrombotic events: Meta-analysis of randomized controlled trials
Fanari, Z., Malodiya, A., Weiss, S. A., Hammami, S., Kolm, P., & Weintraub, W. S. (2016) · Cardiovascular revascularization medicine · doi:10.1016/j.carrev.2016.07.006 · Cited by 36
New directions for pharmacotherapy in the treatment of acute coronary syndrome
Adamski, P., Adamska, U., Ostrowska, M., Koziński, M., & Kubica, J. (2016) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2016.1241234 · Cited by 36
“Regrettably, the authors of the PEGASUS-TIMI 54 study did not provide a net effect analysis of the tested treatment strategies, thus making the results of the trial hard to interpret unambiguously [45].”
Background
Very-low-dose twice-daily aspirin maintains platelet inhibition and improves haemostasis during dual-antiplatelet therapy for acute coronary syndrome
Parker, W. A., Orme, R. C., Hanson, J., Stokes, H. M., Bridge, C. M., Shaw, P. A., Sumaya, W., Thorneycroft, K., Petrucci, G., Porro, B., et al. (2019) · Platelets · doi:10.1080/09537104.2019.1572880 · Cited by 36
“Continuing DAPT with aspirin and reduced-dose ticagrelor longterm in stable high-risk individuals further decreases the riskofMACE compared with aspirin alone [6].”
BackgroundSelf-citation
Long-term antiplatelet therapy following myocardial infarction: implications of PEGASUS-TIMI 54
Parker, W. A., & Storey, R. F. (2016) · Heart · doi:10.1136/heartjnl-2015-307858 · Cited by 35
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Antithrombotic therapy for secondary prevention of atherothrombotic events in cerebrovascular disease
Capodanno, D., Alberts, M. J., & Angiolillo, D. J. (2016) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.111 · Cited by 34
Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54
Dellborg, M., Bonaca, M. P., Storey, R. F., Steg, P. G., Im, K. A., Cohen, M. C., Bhatt, D. L., Ophuis, T. O., Budaj, A., Hamm, C. W., et al. (2019) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvz020 · Cited by 36
Self-citation
Antithrombotic treatment in peripheral artery disease
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Nonculprit Lesion Myocardial Infarction Following Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome
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Self-citation
Acute Coronary Syndrome, Antiplatelet Therapy, and Bleeding: A Clinical Perspective
Tersalvi, G., Biasco, L., Cioffi, G. M., & Pedrazzini, G. B. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9072064 · Cited by 35
“In the PEGASUS-TIMI 54 trial [58], a prolonged DAPT with ticagrelor (90 mg twice daily or 60 mg twice daily) and low-dose aspirin 1 to 3 years after MI showed a significant reduction in cardiovascular death, MI, or stroke compared to aspirin and placebo on a median follow-up of 33 months.”
Method
Polyvascular disease: A narrative review of current evidence and a consideration of the role of antithrombotic therapy
Weissler, E. H., Jones, W. S., Désormais, I., Debus, S., Mazzolai, L., Espinola–Klein, C., Nikol, S., Nehler, M. R., Sillesen, H. H., Aboyans, V., et al. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.11.001 · Cited by 35
Impact of Aspirin and Clopidogrel Hyporesponsiveness in Patients Treated With Drug-Eluting Stents
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Rationale and Design of the Effectiveness of LowEr maintenanCe dose of TicagRelor early After myocardial infarction (ELECTRA) pilot study
Kubica, J., Adamski, P., Buszko, K., Kubica, A., Kuliczkowski, W., Fabiszak, T., Jilma, B., Alexopoulos, D. K., Paciorek, P., & Navarese, E. P. (2017) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvx032 · Cited by 34
Outcomes of Patients with Critical Limb Ischaemia in the EUCLID Trial
Norgren, L., Patel, M. R., Hiatt, W. R., WOJDYLA, D. M., Fowkes, F. G. R., Baumgärtner, I., Mahaffey, K. W., Berger, J. S., Jones, W. S., Katona, B. G., et al. (2017) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2017.11.006 · Cited by 34
Self-citation
Impact of Clopidogrel Therapy on Mortality and Cancer in Patients With Cardiovascular and Cerebrovascular Disease
Elmariah, S., Doros, G. D., Benavente, O., Bhatt, D. L., Connolly, S. J., Yusuf, S., Steinhubl, S. R., Liu, Y., Hsieh, W.-H., Yeh, R. W., et al. (2018) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.117.005795 · Cited by 36
Self-citation
Platelet inhibition with standard vs. lower maintenance dose of ticagrelor early after myocardial infarction (ELECTRA): a randomized, open-label, active-controlled pharmacodynamic and pharmacokinetic study
Kubica, J., Adamski, P., Buszko, K., Barańska, M., Sikora, J., Marszałł, M. P., Sobczak, P., Sikora, A., Kuliczkowski, W., Fabiszak, T., et al. (2019) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvz004 · Cited by 34
Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque
Moss, A. J., Dweck, M. R., Doris, M. K., Andrews, J. P. M., Bing, R., Forsythe, R. O., Cartlidge, T. R. G., Pawade, T., Daghem, M., Raftis, J. B., et al. (2019) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2019.05.023 · Cited by 34
“346 Peripheral vascular disease 8 (4) 7 (4) 1 (1) 6 (6) 0.”
BackgroundInfluential
2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome.
Ueng, K., Chiang, C., Chao, T., Wu, Y., Lee, W.-L., Li, Y., Ting, K.-H., Su, C.-H., Lin, H., Su, T., et al. (2023) · PubMed Central · doi:10.6515/acs.202301_39(1).20221103a · Cited by 34
Ischaemic and bleeding outcomes in elderly patients undergoing a prolonged versus shortened duration of dual antiplatelet therapy after percutaneous coronary intervention: insights from the PRODIGY randomised trial
Piccolo, R., Magnani, G., Ariotti, S., Gargiulo, G., Marino, M., Santucci, A., Franzone, A., Tebaldi, M., Heg, D., Windecker, S., et al. (2017) · EuroIntervention · doi:10.4244/eij-d-16-00497 · Cited by 35
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Update on antithrombotic therapy after percutaneous coronary revascularisation
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Recombinant GPVI-Fc added to single or dual antiplatelet therapy in vitro prevents plaque-induced platelet thrombus formation
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“Dual antiplatelet therapy with aspirin (ASA) and the P2Y12– receptor antagonists such as ticagrelor can reduce cardiovascular mortality or stent thrombosis albeit with limited efficiency and at the cost of increased bleeding risk (11).”
Background
Reversibility of platelet P2Y12 inhibition by platelet supplementation: ex vivo and in vitro comparisons of prasugrel, clopidogrel and ticagrelor
Bertling, A., Fender, A. C., Schüngel, L., Rumpf, M., Mergemeier, K., Geissler, G., Sibrowski, W., Kelsch, R., Waltenberger, J. L., Jakubowski, J. A., et al. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14014 · Cited by 33
Ticagrelor Monotherapy Versus Ticagrelor With Aspirin in Patients With ST-Segment Elevation Myocardial Infarction
Lee, S., Cho, J. Y., Kim, B., Yun, K. H., Suh, Y., Cho, Y., Kim, Y. H., Her, A., Cho, S., Jeon, D. W., et al. (2021) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2020.11.036 · Cited by 33
A review of the effects of ticagrelor on adenosine concentration and its clinical significance
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Trends in Cardiovascular Medicine
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Bleeding in cardiac patients prescribed antithrombotic drugs: electronic health record phenotyping algorithms, incidence, trends and prognosis
Pasea, L., Chung, S., Pujades‐Rodríguez, M., Shah, A. D., Alvarez‐Madrazo, S., Allan, V., Teo, J., Bean, D. M., Sofat, R., Dobson, R., et al. (2019) · BMC Medicine · doi:10.1186/s12916-019-1438-y · Cited by 32
Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis
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Self-citation
Antiplatelet and antithrombotic treatment for secondary prevention in ischaemic heart disease
Lettino, M., Leonardi, S., Maria, E. D., & Halvorsen, S. (2017) · European Journal of Preventive Cardiology · doi:10.1177/2047487317707854 · Cited by 32
Ticagrelor in modern cardiology - an up-to-date review of most important aspects of ticagrelor pharmacotherapy
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“also found to be beneficial for reducing the incidence of cardiovascular death or stroke [27].”
Background
Effect of antiplatelet therapy on cardiovascular and kidney outcomes in patients with chronic kidney disease: a systematic review and meta-analysis
Su, X., Yan, B., Wang, L., Lv, J., Cheng, H., & Chen, Y. (2019) · BMC Nephrology · doi:10.1186/s12882-019-1499-3 · Cited by 32
Dual Pathway Inhibition for Vascular Protection in Patients with Atherosclerotic Disease: Rationale and Review of the Evidence
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2020 Korean Society of Myocardial Infarction Expert Consensus Document on Pharmacotherapy for Acute Myocardial Infarction
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Vulnerable plaque detection: an unrealistic quest or a feasible objective with a clinical value?
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Dyspnea related to reversibly-binding P2Y12 inhibitors: A review of the pathophysiology, clinical presentation and diagnostics
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Self-citation
Impact of Sex on 2-Year Clinical Outcomes in Patients Treated With 6-Month or 24-Month Dual-Antiplatelet Therapy Duration
Gargiulo, G., Ariotti, S., Santucci, A., Piccolo, R., Baldo, A., Franzone, A., Magnani, G., Marino, M., Esposito, G., Windecker, S., et al. (2016) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2016.05.046 · Cited by 31
Self-citation
The risk of bleeding with the use of antiplatelet agents for the treatment of cardiovascular disease
Nathan, A. S., Sen, S., & Yeh, R. W. (2017) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2017.1315101 · Cited by 31
Thrombosis in diabetes: a shear flow effect?
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Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery
Howell, S. J., Hoeks, S. E., West, R. M., Wheatcroft, S. B., Hoeft, A., Leva, B., Plichon, B., Damster, S., Momeni, M., Watremez, C., et al. (2018) · British Journal of Anaesthesia · doi:10.1016/j.bja.2018.09.029 · Cited by 33
“Based on the results of the PEGASUS study, the UK National Institute for Health and Care Excellence now recommends ticagrelor at reduced dose (60 mg bd) for up to 3 yr after the usual 12months course in selected patientswith recentMI.(38,39)”
Result
Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design
Kim, C., Hong, S., Shin, D., Kim, B., Ahn, C., Kim, J., Ko, Y., Choi, D., Hong, M., & Jang, Y. (2019) · American Heart Journal · doi:10.1016/j.ahj.2019.02.015 · Cited by 32
The Two-way Relationship Between Cancer and Atherosclerosis
Raposeiras‐Roubín, S., & Cordero, A. (2019) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2018.12.010 · Cited by 32
Antiplatelet therapy in very elderly and comorbid patients with acute coronary syndromes.
Rosa, R. D., Piscione, F., Galasso, G., Servi, S. D., & Savonitto, S. (2019) · PubMed Central · doi:10.11909/j.issn.1671-5411.2019.02.006 · Cited by 31
Salp15, a Multifunctional Protein From Tick Saliva With Potential Pharmaceutical Effects
Wen, S., Wang, F., Ji, Z., Pan, Y., Jian, M., Bi, Y., Zhou, G., Luo, L., Chen, T., Li, L., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03067 · Cited by 31
Predictors, Type, and Impact of Bleeding on the Net Clinical Benefit of Long‐Term Ticagrelor in Stable Patients With Prior Myocardial Infarction
Magnani, G., Ardissino, D., Im, K., Budaj, A., Storey, R. F., Steg, P. G., Bhatt, D. L., Cohen, M. C., Ophius, T. O., Goudev, A., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.017008 · Cited by 31
Self-citation
Atrial Fibrillation, thromboembolic risk, and the potential role of the natriuretic peptides, a focus on BNP and NT-proBNP – A narrative review
Kerr, B., & Brandon, L. (2022) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2022.101132 · Cited by 34
Dual antiplatelet therapy use by Canadian cardiac surgeons
Yanagawa, B., Ruel, M., Bonneau, C., Lee, M. M., Chung, J. C.-Y., Shouli, S. A., Fagan, A., Khalifa, A. A., White, C. W., Yamashita, M. H., et al. (2015) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2015.08.066 · Cited by 31
Comparing the long-term outcomes in chronic coronary syndrome patients with prior ST-segment and non-ST-segment elevation myocardial infarction: findings from the TIGRIS registry
Krishnamurthy, S. N., Pocock, S., Kaul, P., Owen, R., Goodman, S. G., Granger, C. B., Nicolau, J. C., Simon, T., Westermann, D., Yasuda, S., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2022-070237 · Cited by 32
Self-citation
Progress in the clinical effects and adverse reactions of ticagrelor
Wei, P., Wang, X., Fu, Q., & Cao, B. (2024) · Thrombosis Journal · doi:10.1186/s12959-023-00559-3 · Cited by 34
“In recent study, patients undergoing long-term treatment with ticagrelor were twice as likely to develop gout as those in the placebo group [84].”
Background
Residual cardiovascular risk in coronary artery disease: from pathophysiology to established and novel therapies
Galli, M., Abbate, A., Bonaca, M. P., Crea, F., Forte, M., Frati, G., Gaudino, M. F. L., Gibson, C. M., Gorog, D. A., Mehran, R., et al. (2026) · Nature Reviews Cardiology · doi:10.1038/s41569-026-01249-z · Cited by 41
“However, although prolonged DAPT improves the protection against ischaemic events in patients with high ischaemic risk, the approach also increases the risk of bleeding 131,132 , which necessitates individualized decision-making based on the thrombotic versus haemorrhagic risks 133 .”
Self-citation
Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease
Husted, S., Wallentin, L. C., Andreotti, F., Arnesen, H., Bachmann, F., Baigent, C., Collet, J., Halvorsen, S., Huber, K., Jespersen, J., et al. (2016) · Thrombosis and Haemostasis · doi:10.1160/th15-09-0703 · Cited by 30
Self-citation
Dual antiplatelet therapy after stroke or transient ischaemic attack – how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta‐analysis
Ge, F., Lin, H., Liu, Y., Li, M., Guo, R., Ruan, Z., & Chang, T. (2016) · European Journal of Neurology · doi:10.1111/ene.12982 · Cited by 30
Update on primary PCI for patients with STEMI
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“The Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin (PEGASUS)-TIMI 54 trial enrolled patients with previous MI 1–3 years earlier and randomized half to prolonged DAPT [38].”
BackgroundMethod
Cost-Effectiveness of Long-Term Ticagrelor in Patients With Prior Myocardial Infarction
Magnuson, E. A., Li, H., Wang, K., Vilain, K. R., Shafiq, A., Bonaca, M. P., Bhatt, D. L., Cohen, M. C., Steg, P. G., Storey, R. F., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.05.063 · Cited by 30
Self-citation
Ticagrelor, a P2Y12 antagonist, attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein-E-deficient mice
Ganbaatar, B., Fukuda, D., Salim, H. M., Nishimoto, S., Tanaka, K., Higashikuni, Y., Hirata, Y., Yagi, S., Soeki, T., & Sata, M. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.05.053 · Cited by 30
Updated Recommendations on Cardiovascular Prevention in 2022: An Executive Document of the Italian Society of Cardiovascular Prevention
Volpe, M., Gallo, G., Modena, M. G., Ferri, C., Desideri, G., Tocci, G., Members of the Board of the Italian Society of Cardiovascular Prevention, Bellone, S., Bertolotti, M., Biffi, A., et al. (2022) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-021-00503-4 · Cited by 30
Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis
Kim, W., Mun, J.-Y., Baek, S.-W., Kim, M., Yang, G., Jeong, M.-S., Choi, S. Y., Han, J.-Y., Kim, M. H., & Leem, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179596 · Cited by 30
“In addition, ticagrelor administration was correlated with cancer development in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI) clinical trial [16,21].”
Method

Authors: Bonaca, M. P., Bhatt, D. L., Cohen, M., Steg, P. G., Storey, R. F., Jensen, E. C., Magnani, G., Bansilal, S., Fish, M. P., Im, K., Bengtsson, O., Ophuis, T. O., Budaj, A., Theroux, P., Ruda, M., Hamm, C., Goto, S., Spinar, J., Nicolau, J. C., Kiss, R. G., Murphy, S. A., Wiviott, S. D., Held, P., Braunwald, E., & Sabatine, M. S.
Affiliations: Newark Beth Israel Medical Center (US)
Brigham and Women's Hospital (US)
University of Sheffield (GB)
AstraZeneca (Sweden) (SE)
Icahn School of Medicine at Mount Sinai (US)
Canisius-Wilhelmina Ziekenhuis (NL)
Grochowski Hospital (PL)
National Medical Research Center of Cardiology (RU)
Justus-Liebig-Universität Gießen (DE)
Tokai University (JP)
Universidade de São Paulo (BR)
ORCID: Bonaca, Marc P.
Bhatt, Deepak L.
Cohen, Marc
Storey, Robert F.
Magnani, Giulia
Im, Kyungah
Bengtsson, Olof
Budaj, Andrzej
Hamm, Christian
Goto, Shinya
Nicolau, José Carlos
Murphy, Sabina A.
Wiviott, Stephen D.
Sabatine, Marc S.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2015-05-07
Volume: 372
Issue: 19
Pages: 1791-1800
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1500857
OpenAlex: W2141358924
Cited by: 1,999
References: 32
Citations by year: 2026: 86 · 2025: 99 · 2024: 102 · 2023: 130 · 2022: 163 · 2021: 189 · 2020: 232 · 2019: 205 · 2018: 220 · 2017: 222 · 2016: 236 · 2015: 108
FWCI: 188.81
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
HAL (submittedVersion)
University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
Digital Access to Libraries (submittedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Use Siena air (University of Siena) (submittedVersion)
Funders: Japan Society for the Promotion of Science (24390202)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Coronary Interventions and Diagnostics
Keywords: ticagrelor, P2Y12 inhibitors, old myocardial infarction, dual antiplatelet therapy, long-term antiplatelet therapy, cardiovascular mortality, myocardial infarction, stroke, intracranial hemorrhage, aspirin, dose comparison, secondary prevention, bleeding risk, cardiovascular risk reduction
MeSH terms: Ticagrelor, Adenosine, Aged, Aspirin, Cardiovascular Diseases, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Hemorrhage, Humans, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Risk, Intracranial Hemorrhages, Kaplan-Meier Estimate, Secondary Prevention, Purinergic P2Y Receptor Antagonists

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Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction

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