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Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction
Open accessAbstract
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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“No sufficient safety and efficacy data are available for DAPT with reduced-dose ticagrelor beyond 3 years”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [317]
In the citing paper
“Reduced-dose ticagrelor (60 mg) decreased MACE compared with placebo (7.77% vs. 9.04%, respectively; HR 0.84; 95% CI, 0.74-0.95;P = 0.004; NNT 79), with no heterogeneity with respect to the diabetes sub-group”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [317]
In the citing paper
“whereas it significantly increased TIMI major bleeding (2.3% vs. 1.06%, respectively; HR 2.32; 95% CI, 1.68-3.21;NNH 81)”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [317]
In the citing paper
“dyspnoea, serious adverse events, and drug discontinuation rates.317”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [317]
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“guidelines do not directly address this chronic phase of disease [2-4] and yet recent trials found that dual antiplatelet therapy continued beyond the first year after acute MI lowers the risk of cardiovascular death, MI, and stroke [5, 6].”
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“Lastly, unlike clopidogrel, ticagrelor retained some efficacy to prevent ischemic events over and above those of aspirin during chronic therapy [8].”
BackgroundLiang, Y., Zhu, J., Liu, L., Anand, S. S., Connolly, S. J., Bosch, J., Guzik, T. J., O'Donnell, M. J., Dagenais, G. R., Fox, K. A. A., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa100 · Cited by 26
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“Recently, accumulating data support extended DAPT beyond 1 year after ACS, especially for patients with MI [1,18,19].”
BackgroundKupka, D., & Sibbing, D. (2018) · Korean Circulation Journal · doi:10.4070/kcj.2018.0255 · Cited by 24
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“78 eGFR CKD-EPI b15 ml/min 0 0 93 STEMI, ST elevationmyocardial infarction; FMC,firstmedical contact; h, hours; PCI, percutaneou receptor blocker; COPD, chronic obstructive pulmonary disease; BP, blood pressure; GRACE [ Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AH [23], bl…”
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Ticagrelor versus clopidogrel in patients with STEMI treated with thrombolysis: the MIRTOS trial
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“For instance, there are important risk reductions with new therapies for LDL-lowering(6) and relating to antithrombotic therapy.(7,8) Identifying the spectrum of risk in stable patients eligible for such treatments will identify those high-risk patients for whom the absolute reduction will be greatest.”
BackgroundSelf-citationAntithrombotic therapy for patients with chronic coronary syndromes
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Self-citationTicagrelor or Prasugrel in Acute Coronary Syndromes — The Winner Takes It All?
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Current Antithrombotic Treatments for Cardiovascular Diseases: A Comprehensive Review
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“The studied population, at high ischemic risk without recent bleeding or anticoagulation indications, may not represent all MI patients, especially those with different risk profiles [30].”
BackgroundMethodInfluentialTicagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis
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Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents
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“…have been demonstrated to significantly reduce recurrent MACE in this population: prolonged DAPT, which combines P2Y12 receptor antagonists, preferably ticagrelor 60 mg with aspirin [13], or a dual-pathway inhibition (DPI) approach, which combines a low-dose of rivaroxaban (2.5 mg) and aspirin [15].”
BackgroundInfluentialPerspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization
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Treatment of stable ischaemic heart disease: the old and the new
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Efficacy and safety of newer P2Y12 inhibitors for acute coronary syndrome: a network meta-analysis
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“However, several studies demonstrated extended treatment with aspirin and a P2Y12 inhibitor beyond 1 year after coronary stenting was associated with reduction in the rate of major adverse cardiovascular and cerebrovascular events and increase in the rate of bleeding events (12,13).”
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A critical reappraisal of aspirin for secondary prevention in patients with ischemic heart disease
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“04% over the subsequent 1 to 2 years which has a modest reduced with clopidogrel monotherapy or DAPT.(13,18,19) In these same trials, ASA monotherapy”
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“The PEGASUS-TIMI 54 study [2] included 1161 patients with a history of MI at 1 to 3 years prior to enrolment and at high risk of an atherothrombotic event.”
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Central apnoeas and ticagrelor-related dyspnoea in patients with acute coronary syndrome
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Metadata
- 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
- 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
- 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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