A Comprehensive Review of the Pleiotropic Effects of Ticagrelor

Triska, Jeffrey; Maitra, Neil; Deshotels, Matthew R.; Haddadin, Faris; Angiolillo, Dominick J.; Vilahur, Gemma; Jneid, Hani; Atar, Dan; Birnbaum, Yochai

doi:10.1007/s10557-022-07373-5

Cited by 6 publications

(2 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It remains unclear whether this finding on clopidogrel reflects chance or a loss of protective effects of aspirin beyond its antiplatelet activity in clopidogrel-treated but not in ticagrelor-treated patients. Ticagrelor, unlike clopidogrel and similar to aspirin, has been associated with pleiotropic outcomes that seem to be unrelated to platelet inhibition …”

Section: Discussionmentioning

confidence: 99%

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Valgimigli,

Gragnano,

Branca

et al. 2024

JAMA Cardiol

Self Cite

View full text Add to dashboard Cite

ImportanceAmong patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor.ObjectiveTo assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI.Data SourcesMEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction.Study SelectionIncluded studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI.Data Extraction and SynthesisPatient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data.Main Outcomes and MeasuresThe primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding.ResultsAnalyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority &gt; .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P &lt; .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P &lt; .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04).Conclusions and RelevanceThis systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

show abstract

Section: Discussionmentioning

confidence: 99%

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Valgimigli,

Gragnano,

Branca

et al. 2024

JAMA Cardiol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further investigations are required to determine whether these P2Y 12 -independent effects provide unexpected advantages to the immune system and, therefore, can be employed as inflammatory drugs. On the other hand, it could also cause negative effects, especially when administered in combination with other drugs [ 84 ].…”

Section: Drugs Targeting P2y 12mentioning

confidence: 99%

The Signaling Pathway of the ADP Receptor P2Y12 in the Immune System: Recent Discoveries and New Challenges

Entsie

Kong

Amoafo

et al. 2023

IJMS

View full text Add to dashboard Cite

P2Y12 is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y12 has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y12 is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y12 could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y12 in the cells of the immune system and the effect of P2Y12 activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome.

show abstract

Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study

Mathew

Sidhu

Rihal

et al. 2022

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

A Comprehensive Review of the Pleiotropic Effects of Ticagrelor

Cited by 6 publications

References 94 publications

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

The Signaling Pathway of the ADP Receptor P2Y12 in the Immune System: Recent Discoveries and New Challenges

Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study

Contact Info

Product

Resources

About