Oral Antiplatelet Therapy After Acute Coronary Syndrome

Kamran, H; Jneid, Hani; Kayani, Waleed Tallat; Virani, Salim S.; Levine, Glenn N.; Nambi, Vijay; Khalid, Umair

doi:10.1001/jama.2021.0716

Cited by 70 publications

(41 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While P2XRs are implicated in a host of physiological and pathophysiological conditions found within the cardiovascular, central nervous, and immune systems, there are no FDA-approved drugs targeting this receptor family. The success of antiplatelet drugs which antagonize the related P2Y GPCR family exemplifies the therapeutic value of targeting purinergic signaling (Kamran et al, 2021). To this point, there remains substantial untapped therapeutic potential for P2XR modulation.…”

Section: Discussionmentioning

confidence: 99%

Molecular Pharmacology of P2X Receptors: Exploring Druggable Domains Revealed by Structural Biology

Oken

Krishnamurthy²,

Savage³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Extracellular ATP is a critical signaling molecule that is found in a wide range of concentrations across cellular environments. The family of nonselective cation channels that sense extracellular ATP, termed P2X receptors (P2XRs), is composed of seven subtypes (P2X1-P2X7) that assemble as functional homotrimeric and heterotrimeric ion channels. Each P2XR is activated by a distinct concentration of extracellular ATP, spanning from high nanomolar to low millimolar. P2XRs are implicated in a variety of physiological and pathophysiological processes in the cardiovascular, immune, and central nervous systems, corresponding to the spatiotemporal expression, regulation, and activation of each subtype. The therapeutic potential of P2XRs is an emerging area of research in which structural biology has seemingly exceeded medicinal chemistry, as there are several published P2XR structures but currently no FDA-approved drugs targeting these ion channels. Cryogenic electron microscopy is ideally suited to facilitate structure-based drug design for P2XRs by revealing and characterizing novel ligand-binding sites. This review covers structural elements in P2XRs including the extracellular orthosteric ATP-binding site, extracellular allosteric modulator sites, channel pore, and cytoplasmic substructures, with an emphasis on potential therapeutic ligand development.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Pharmacology of P2X Receptors: Exploring Druggable Domains Revealed by Structural Biology

Oken

Krishnamurthy²,

Savage³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Besides, acute coronary syndrome (ACS), as a common and serious CVD, has a dramatically increased incidence with age, proposing a great challenge to public medical care. Dual antiplatelet therapy (DAPT) is the mainstay treatment strategy for ACS, with timely vascularization as needed (2,3). As for the choice of antiplatelet agent, ticagrelor is recommended over clopidogrel for patients with ACS or who have received the percutaneous coronary intervention (PCI) in the 2016 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines and the 2018 European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines (2,4).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Clinical Outcomes Between Ticagrelor and Clopidogrel in Acute Coronary Syndrome: A Comprehensive Meta-Analysis

Sun

Cui

2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundTicagrelor is currently recommended for patients with the acute coronary syndrome (ACS). However, recent studies have yielded controversial results.ObjectiveTo compare the clinical outcomes between ticagrelor and clopidogrel in patients with ACS.MethodsThree electronic databases were queried until April 25, 2021. We defined major adverse cardiovascular events (MACEs) as the primary efficacy endpoint. The secondary efficacy endpoints included stroke, stent thrombosis, cardiovascular death, all-cause death, and myocardial infarction. The safety endpoints were (major and minor) bleeding. Odds ratios (ORs) and 95% CIs were calculated to represent the estimated effect sizes.ResultsA total of 270,937 patients with ACS from 10 clinical trials and 18 observational studies were included. No significant difference was detected in MACE (OR 0.81, 95% CI 0.60–1.08, p = 0.15, I2 = 64.83%). However, ticagrelor introduced a higher risk of bleeding (1.46, 1.17–1.83, 0.00, 61.66%) and minor bleeding (1.71, 1.33–2.21, 0.00, 4.65%) in clinical trials. The results of secondary efficacy endpoints differed in the clinical trials and observational studies. Subgroup analysis demonstrated that ticagrelor showed better therapeutic effects in patients who underwent the percutaneous coronary intervention (PCI) (0.38, 0.23–0.63, 0.00, 0) than those intended for PCI (1.03, 0.76–1.38, 0.87, 64.26%). Meanwhile, ticagrelor showed different therapeutic effects on patients with ACS of different ethnicities and different countries.ConclusionThis meta-analysis demonstrated that ticagrelor is not superior to clopidogrel in MACE but is associated with a higher risk of bleeding in patients with ACS. Different PCI strategies, ethnicities, and countries may be the factors that contribute to different therapeutic effects of ticagrelor.Systematic Review RegistrationThis study is registered with PROSPERO (CRD42021251212).

show abstract

“…Among LT candidates, it is frequent to find indications for aspirin with or without P2Y12 inhibitors in bearers of coronary stents or as secondary prevention of noncardioembolic ischemic stroke. 21 , 22 Again, the scientific evidence supporting antiplatelet therapies in patients with advanced liver disease is scarce and their use is considered of high risk, particularly in patients with severe thrombocytopenia.…”

Section: Methodsmentioning

confidence: 99%

Consensus Statement on Hemostatic Management, Anticoagulation, and Antiplatelet Therapy in Liver Transplantation

et al. 2022

View full text Add to dashboard Cite

show abstract

Oral Antiplatelet Therapy After Acute Coronary Syndrome

Abstract: This narrative review summarizes oral antiplatelet therapy and specifically addresses the effects of dual antiplatelet therapy for patients with acute coronary syndrome who have not taken anticoagulants.

Cited by 70 publications

References 72 publications

Molecular Pharmacology of P2X Receptors: Exploring Druggable Domains Revealed by Structural Biology

Molecular Pharmacology of P2X Receptors: Exploring Druggable Domains Revealed by Structural Biology

Comparison of Clinical Outcomes Between Ticagrelor and Clopidogrel in Acute Coronary Syndrome: A Comprehensive Meta-Analysis

Consensus Statement on Hemostatic Management, Anticoagulation, and Antiplatelet Therapy in Liver Transplantation

Contact Info

Product

Resources

About