Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

Schnorbus, Boris; Daiber, Andreas; Jurk, Kerstin; Warnke, Silke; Koenig, Jochem; Lackner, Karl J.; Münzel, Thomas; Gori, Tommaso

doi:10.1093/eurheartj/ehz917

Cited by 61 publications

(53 citation statements)

References 52 publications

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“…Platelets have been recognized as crucial regulators of inflammatory processes under various pathophysiological conditions ( Karhausen et al, 2020 ). The inflammation caused by overactivated platelets can further promote the development of thrombosis, atherosclerosis, and cardiovascular diseases ( Barrett et al, 2019 ; Garshick et al, 2020 ; Schnorbus et al, 2020 ). Platelets exert critical roles in the development of inflammatory diseases such as inflammatory bowel disease (IBD) ( Chimen et al, 2019 ; Petrey et al, 2019 ; Nicolai and Massberg, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

et al. 2020

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Background: Increased platelet count has been reported in ankylosing spondylitis (AS) patients, but its clinical significance is still largely elusive. The objective of this study was to evaluate the clinical role of platelet count in AS patients, especially its impact on treatment outcomes. Methods: A case-control study containing 35 AS patients receiving anti-tumor necrosis factor-α (anti-TNF-α) therapy and 45 healthy controls was performed, and AS patients were followed at least 6 months after anti-TNF-α therapy. A systematic review and metaanalysis of studies containing relevant data on outcomes of interest was also performed. Results: AS patients had significantly higher platelet count than controls (p 0.0001), and the significantly increased platelet count in AS patients was confirmed in a metaanalysis of 14 studies involving 1,223 AS patients and 913 controls (mean difference 39.61, 95% CI 27.89-51.34, p < 0.001). Besides, platelet count was significantly correlated with ESR (p < 0.001) and was moderately correlated with ASDAS-CRP score (p 0.002). Moreover, anti-TNF-α therapy could reduce platelet count in AS patients at the first month and the effect was maintained through the treatment duration. In the prospective follow-up study of those 35 AS patients, those responders to anti-TNF-α therapy had significantly lower platelet count than nonresponders (p 0.015). Logistic regression analysis suggested that lower platelet count was associated with higher possibility of achieving good response to anti-TNF-α therapy in AS patients (odds ratio 2.26; 95% CI 1.06-4.82; p 0.035). Conclusion: This study suggested that platelet count was associated with inflammation severity and treatment outcomes in AS patients, and elevated platelet count was a promising biomarker of poorer response to anti-TNF-α therapy. The findings above need to be validated in more future studies.

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Section: Introductionmentioning

confidence: 99%

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

et al. 2020

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“…In diabetic patients presented with non-ST-segment elevation ACS [ 31 ], ticagrelor showed better improvement of endothelial function (indicated by FMD) compared to prasugrel, which has been explained by an increased adenosine level. However, other studies reported that ticagrelor did not improve endothelial function compared to prasugrel and clopidogrel [ 32 ]; rather, endothelial function was improved during prasugrel treatment [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Monotherapy with Clopidogrel vs. Aspirin on Vascular Function and Hemostatic Measurements in Patients with Coronary Artery Disease: The Prospective, Crossover I-LOVE-MONO Trial

Park

Kang

Ahn

et al. 2021

JCM

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To evaluate the effect of clopidogrel vs. aspirin monotherapy on vascular function and hemostatic measurement. Background: Monotherapy with P2Y12 receptor inhibitor vs. aspirin can be a useful alterative to optimize clinical efficacy and safety in high-risk patients with coronary artery disease (CAD). Methods: We performed a randomized, open-label, two-period crossover study in stented patients receiving at least 6-month of dual antiplatelet therapy (DAPT). Thirty CAD patients with moderate-to-high ischemic risk were randomly assigned to receive either 75 mg of clopidogrel or 100 mg of aspirin daily for 4 weeks, and were crossed over to the other strategy for 4 weeks. Vascular function was evaluated with reactive hyperemia-peripheral arterial tonometry (RH-PAT) and brachial-ankle pulse wave velocity (baPWV). Hemostatic profiles were measured with VerifyNow and thromboelastography (TEG). The primary endpoint was the reactive hyperemia index (RHI) during clopidogrel or aspirin monotherapy. Results: Clopidogrel vs. aspirin monotherapy was associated with better endothelial function (RHI: 2.11 ± 0.77% vs. 1.87 ± 0.72%, p = 0.045), lower platelet reactivity (130 ± 64 vs. 214 ± 50 P2Y12 reaction unit [PRU], p < 0.001) and prolonged reaction time (TEG R: 5.5 ± 1.2 vs. 5.1 ± 1.1 min, p = 0.037). In multivariate analysis, normal endothelial function (RHI ≥ 2.1) was significantly associated with clot kinetics (TEG angle ≤ 68 degree) and ‘PRU ≤ 132’. ‘PRU ≤ 132’ was achieved in 46.2% vs. 3.8% during clopidogrel administration vs. aspirin monotherapy (odds ratio 21.4, 95% confidence interval 2.7 to 170.1, p < 0.001). Conclusions: In CAD patients, clopidogrel vs. aspirin monotherapy was associated with better endothelial function, greater platelet inhibition and lower coagulation activity, suggesting pleiotropic effects of clopidogrel on endothelial function and hemostatic profiles.

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“…In fact, another study recently reported prasugrel to better prevent the endothelial dysfunction and inflammation associated with coronary stenting and NSTEMI, as compared with clopidogrel or ticagrelor. 63 Following these results, the 2020 ESC guidelines have granted a class IIb evidence favoring prasugrel over ticagrelor in patients with NSTEMI undergoing PCI, and for whom use of potent P2Y12 inhibitors is indicated. The loading dose of P2Y12 inhibitors may be administered as soon as the coronary angiogram is performed and prior to PCI.…”

Section: Which P2y 12 Inhibitors In the Acute Setting?mentioning

confidence: 99%

Antithrombotic Therapy in Acute Coronary Syndromes: Current Evidence and Ongoing Issues Regarding Early and Late Management

Guedeney

Collet

2021

Thromb Haemost

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A few decades ago, the understanding of the pathophysiological processes involved in the coronary artery thrombus formation has placed anticoagulant and antiplatelet agents at the core of the management of acute coronary syndrome (ACS). Increasingly potent antithrombotic agents have since been evaluated, in various association, timing, or dosage, in numerous randomized controlled trials to interrupt the initial thrombus formation, prevent ischemic complications, and ultimately improve survival. Primary percutaneous coronary intervention, initial parenteral anticoagulation, and dual antiplatelet therapy with potent P2Y12 inhibitors have become the hallmark of ACS management revolutionizing its prognosis. Despite these many improvements, much more remains to be done to optimize the onset of action of the various antithrombotic therapies, for further treating and preventing thrombotic events without exposing the patients to an unbearable hemorrhagic risk. The availability of various potent P2Y12 inhibitors has opened the door for individualized therapeutic strategies based on the clinical setting as well as the ischemic and bleeding risk of the patients, while the added value of aspirin has been recently challenged. The strategy of dual-pathway inhibition with P2Y12 inhibitors and low-dose non-vitamin K antagonist oral anticoagulant has brought promising results for the early and late management of patients presenting with ACS with and without indication for oral anticoagulation. In this updated review, we aimed at describing the evidence supporting the current gold standard of antithrombotic management of ACS. More importantly, we provide an overview of some of the ongoing issues and promising therapeutic strategies of this ever-evolving topic.

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Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

Cited by 61 publications

References 52 publications

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

Effects of Monotherapy with Clopidogrel vs. Aspirin on Vascular Function and Hemostatic Measurements in Patients with Coronary Artery Disease: The Prospective, Crossover I-LOVE-MONO Trial

Antithrombotic Therapy in Acute Coronary Syndromes: Current Evidence and Ongoing Issues Regarding Early and Late Management

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