Association of potent P2Y12 blockers with ischemic and bleeding outcomes in non-ST-segment elevation myocardial infarction

Sim, Doo Sun; Jeong, Myung Ho; Kim, Hyo Soo; Gwon, Hyeon Cheol; Seung, Ki Bae; Rha, Seung Woon; Chae, Shung Chull; Kim, Chong Jin; Soo, Kwang; Yoon, Jung Han; Chae, Jei Keon; Joo, Seung Jae; Choi, Dong Ju; Hur, Seung Ho; Seong, In Whan; Cho, Myeong Chan; Kim, Doo Il; Oh, Seok Kyu; Ahn, Tae Hoon; Hwang, Jin Yong; investigators, Kamir-Nih registry

doi:10.1016/j.jjcc.2018.09.002

Cited by 6 publications

(6 citation statements)

References 41 publications

(42 reference statements)

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“…No significant differences were observed in the incidence of major bleeding between the ticagrelor group and the clopidogrel group. Previous studies have compared the efficacy and safety of ticagrelor vs. clopidogrel in patients with ACS, AMI, STEMI, NSTEMI, and NSTE-ACS [10][11][12][13][14] . However, there is currently no study comparing the efficacy and safety of ticagrelor vs. clopidogrel in patients with SCAD undergoing PCI.…”

Section: Resultsmentioning

confidence: 99%

“…Some studies showed that ticagrelor was associated with an increased risk of bleeding events compared with clopidogrel in patients with AMI 11,[28][29] , NSTEMI 13) , and ACS [30][31][32] . However, the PLATO study and other studies revealed that ticagrelor did not increase the bleeding risk compared with clopidogrel in patients with ACS 33) , NSTE-ACS 14) , and STEMI 12,34) .…”

Section: Resultsmentioning

confidence: 99%

“…The Platelet Inhibition and Patient Outcomes (PLATO) trial and other studies have compared the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome (ACS), acute myocardial infarction (AMI), ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), or non-STsegment elevation acute coronary syndrome (NSTE-ACS) [10][11][12][13][14] . No other previous study comprehensively evaluated the efficacy and safety of ticagrelor in patients with SCAD for a 1-year follow-up period.…”

Section: Treatmentmentioning

confidence: 99%

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Efficacy and Safety of Ticagrelor and Clopidogrel in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Qiu

et al. 2021

JAT

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The efficacy and safety of ticagrelor and clopidogrel in patients with stable coronary artery disease (SCAD) undergoing percutaneous coronary intervention (PCI) remain uncertain. Thus, this study aimed to compare the efficacy and safety of ticagrelor and clopidogrel in patients with SCAD treated with PCI. Methods: A total of 9,379 patients with SCAD undergoing PCI who received dual antiplatelet therapy (DAPT) were consecutively enrolled in two groups, namely, ticagrelor (n 1,081) and clopidogrel (n 8,298) groups. Major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding events according to ticagrelor or clopidogrel use were compared. Results: After propensity matching (n 1,081 in each group), ticagrelor was associated with fewer MACCEs compared with clopidogrel (3.6% vs. 5.7%, hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41-0.93, p 0.019), and the difference between ticagrelor and clopidogrel for bleeding events was nonsignificant (1.7% vs. 1.2%, HR 1.39, 95% CI 0.68-2.85, p 0.366). On the other hand, the difference between ticagrelor and clopidogrel for net adverse clinical events was significant (4.1% vs. 6.0%, HR 0.67, 95% CI 0.46-0.98, p 0.039). In a multivariate analysis, the use of ticagrelor, number of stents, previous history of diabetes, previous history of smoking, and ACC/AHA type B2 or C lesions were considered independent predictors of MACCEs, while radial artery access, previous history of stroke, and weight 60kg were independent predictors of bleeding events. Conclusions: Ticagrelor was associated with a lower incidence of MACCEs without an increased risk of bleeding events in patients with SCAD receiving PCI. Thus, to overcome the shortcomings of clopidogrel, a new generation of antiplatelet drugs, namely, prasugrel and ticagrelor, has been developed 6). Ticagrelor is a reversible, nonthienopyridine, P2Y12 oral inhibitor that has a faster onset and offset of action and a higher inhibitory effect on platelet aggregation compared with clopidogrel 7) , which requires metabolic activation through a multistep process involving multiple cytochrome P450 isoenzymes 8). Ticagrelor can bind directly to the P2Y12 receptor and inhibit platelet aggregation induced by Copyright©2020 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Efficacy and Safety of Ticagrelor and Clopidogrel in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Qiu

et al. 2021

JAT

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“…Globally, clopidogrel is the most frequently used P2Y12 inhibitor in both ACS and CCS, accounting for about 50% to 80% of cases of P2Y12 inhibitor use worldwide [ 13 , 14 , 15 , 16 , 17 ]. However, our data showed that clopidogrel was used only in 24% of patients, while prasugrel was used in 76% of patients in the Japanese ACS registry.…”

Section: Discussionmentioning

confidence: 99%

A Japanese Dose of Prasugrel versus a Standard Dose of Clopidogrel in Patients with Acute Myocardial Infarction from the K-ACTIVE Registry

Mori

Mizukami

Maeda

et al. 2022

JCM

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Background: Dual antiplatelet therapy (DAPT) with aspirin plus P2Y12 inhibitor is used as a standard therapy for patients with acute myocardial infarction (AMI) treated with drug-eluting stents (DESs). In Japan, clopidogrel was the major P2Y12 inhibitor used for a decade until the new P2Y12 inhibitor, prasugrel, was introduced. Based on clinical studies considering Japanese features, the set dose for prasugrel was reduced to 20 mg as a loading dose (LD) and 3.75 mg as a maintenance dose (MD); these values are 60 and 10 mg, respectively, globally. Despite this dose discrepancy, little real-world clinical data regarding its efficacy and safety exist. Methods: From the K-ACTIVE registry, based on the DAPT regimen, patients were divided into a prasugrel group and a clopidogrel group. The ischemic event was a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. The bleeding event was type 3 or 5 bleeding based on the Bleeding Academic Research Consortium (BARC) criteria. Results: Substantially more patients were prescribed prasugrel (n = 2786) than clopidogrel (n = 890). Clopidogrel tended to be selected over prasugrel in older patients with numerous comorbidities. Before adjustments were made, the cumulative incidence of ischemic events at 1 year was significantly greater in the clopidogrel group than in the prasugrel group (p = 0.007), while the cumulative incidence of bleeding events at 1 year was comparable between the groups (p = 0.131). After adjustments were made for the age, sex, body weight, creatine level, type of AMI, history of MI, approach site, oral anticoagulation therapy, presence of multivessel disease, Killip classification, and presence of intra-aortic balloon pumping, both ischemic and bleeding events became comparable between the groups. Conclusion: A Japanese dose of prasugrel was commonly used in AMI patients in the real-world database. Both the prasugrel and clopidogrel groups showed comparable rates of 1 year ischemic and bleeding events.

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“…The occlusive effect of these aggregates combines with their inherent instability and tendency to embolic distal circulation. Thus, this aggregation mechanism may enhance cerebral blood vessel symptoms of acute coronary syndrome and intermittent thromboembolism [71]. In addition, this aggregation process can occur independent of soluble agonists, further illustrating the important role of platelet aggregation mechanism driven by hemodynamic changes [11].…”

Section: P2y12 Receptor and Atherosclerosismentioning

confidence: 95%

The Role and Molecular Mechanism of P2Y12 Receptors in the Pathogenesis of Atherosclerotic Cardiovascular Diseases

Wang

et al. 2021

Applied Sciences

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The P2Y receptor family is a class of G protein-coupled receptors activated primarily by adenosine triphosphate (ATP), adenosine diphosphate (ADP), uridine triphosphate (UTP) and uridine diphosphate (UDP). The P2Y12 receptor is expressed on platelets which mediates platelet aggregation and morphological changes. At the same time, during the process of vascular remodeling and atherosclerosis, ADP can also promote the migration and proliferation of vascular smooth muscle and endothelial cells through P2Y12 receptor activating. Furthermore, P2Y12 is involved in many signal transductions processes, such as intimal hyperplasia, monocyte infiltration and so on, which play an important role in immune inflammation and brain injury. In order to solve the diseases induced by P2Y12 receptor, inhibitors such as ticagrelor, clopidogrel were widely used for cardiovascular diseases. However, there were some problems, such as limited antithrombotic effect, remain unsolved. This article summarizes the role and molecular mechanism of P2Y12 receptors in the pathogenesis of cardiovascular-related diseases, providing in-depth expounding on the molecular mechanism of P2Y12 receptor inhibitors and contributing to the treatment of diseases based on P2Y12 receptors.

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Association of potent P2Y12 blockers with ischemic and bleeding outcomes in non-ST-segment elevation myocardial infarction

Cited by 6 publications

References 41 publications

Efficacy and Safety of Ticagrelor and Clopidogrel in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Efficacy and Safety of Ticagrelor and Clopidogrel in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

A Japanese Dose of Prasugrel versus a Standard Dose of Clopidogrel in Patients with Acute Myocardial Infarction from the K-ACTIVE Registry

The Role and Molecular Mechanism of P2Y12 Receptors in the Pathogenesis of Atherosclerotic Cardiovascular Diseases

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