Efficacy and Safety of Loading Doses With P2Y12-Receptor Antagonists in Patients Without Dual Antiplatelet Therapy Undergoing Elective Coronary Intervention

2019 ◽  
Vol 73 (1) ◽  
pp. 56-59 ◽  
Author(s):  
Jesús Piqueras-Flores ◽  
Alfonso Jurado-Román ◽  
María Thiscal López-Lluva ◽  
Ignacio Sánchez-Pérez ◽  
José Abellán-Huerta ◽  
...  
2013 ◽  
pp. 88-95
Author(s):  
Gianluca Airoldi ◽  
Mauro Campanini

Antiplatelet drugs are the cornerstone of treatment for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention. Clopidogrel and aspirin improve long-term vascular clinical outcomes in these patients and have become a standard of care. However, many patients still experience ischemic/thrombotic events, and it appears that insufficient response to both aspirin and clopidogrel contribute to this failure. Newer P2Y12 receptor blocker therapy resulted in only an approximately 2% reduction in absolute risk compared with clopidogrel. This indicates that residual ischemic events are mediated by other pathways that are unblocked by current dual antiplatelet therapy. Thrombin is the most potent platelet agonist (over 1000 times more than adenosine diphosphate on a molar basis). Thrombin-mediated platelet activation depends on proteaseactivated receptor (PAR) binding. PAR-1 is the main receptor for thrombin on human platelets; PAR-4 may contribute to platelet activation at much higher concentrations of thrombin. Inhibition of the PAR-1 may provide additional benefits over the standard dual antiplatelet therapy in attenuating ischemic event in patients with ACS. Vorapaxar is a new highly selective oral PAR-1 antagonist that inhibits thrombin-induced platelet activation. We review the pharmacokinetic, pharmacodynamic and clinical profile of vorapaxar. Although preliminary data indicated that vorapaxar may have the potential to improve ischemic outcomes without significantly increasing bleeding, more recent larger clinical trials seem to be less optimistic about both its effectiveness and safety. At this time, the role of vorapaxar in the settings of atherothrombotic disorders is not clear. Although it may be associated with less bleeding than P2Y12 receptor blockers, its antithrombotic effectiveness and side effects are major concerns.


2021 ◽  
Vol 26 (7) ◽  
pp. 4525
Author(s):  
S. B. Aksentiev ◽  
A. V. Solovieva ◽  
D. S. Yunevich

Aim. To compare the efficacy and safety of prasugrel, ticagrelor, or clopidogrel as part of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) due to myocardial infarction (MI).Material and methods. The observational study included 74 patients who underwent PCI due to MI within the first 24 hours after the onset. The patients were devided into 3 groups: group 1 — patients who received ticagrelor as part of DAPT; group 2 — clopidogrel, group 3 — prasugrel. The follow-up period was 28 days. To assess the efficacy and safety of therapy, a composite endpoint was assessed (death + nonfatal recurrent MI (and/or stent rethrombosis) + nonfatal ischemic stroke (IS). Additional secondary endpoints were any moderate and severe (major) bleeding according to the GUSTO and/or TIMI scales. We assessed the incidence of reperfusion arrhythmias, an opening of an infarct-related coronary artery (IRCA), and non-ST elevation myocardial infarction (non-STEMI).Results. The analysis showed no significant differences in the cumulative incidence of adverse outcomes in the study groups within 28 days. The prevalence of secondary endpoints over a 28-day follow-up period was 3,1% in the ticagrelor group and 5,9% in the clopidogrel group, while no moderate and life-threatening bleeding was recorded in the prasugrel group during. There were no significant differences in the incidence of reperfusion arrhythmias, opening of an IRCA, and non-STEMI between the groups.Conclusion. The obtained results suggest the comparable efficacy and safety profiles of prasugrel, ticagrelor and clopidogrel as a part of DAPT in patients undergoing PCI due to MI. There were no significant differences in endpoint event rates. In particular, prasugrel has been shown to be as effective and safe as ticagrelor.


2020 ◽  
Vol 14 ◽  
Author(s):  
Johny Nicolas ◽  
Usman Baber ◽  
Roxana Mehran

A P2Y12 inhibitor-based monotherapy after a short period of dual antiplatelet therapy is emerging as a plausible strategy to decrease bleeding events in high-risk patients receiving dual antiplatelet therapy after percutaneous coronary intervention. Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT), a randomized double-blind trial, tested this approach by dropping aspirin at 3 months and continuing with ticagrelor monotherapy for an additional 12 months. The study enrolled 9,006 patients, of whom 7,119 who tolerated 3 months of dual antiplatelet therapy were randomized after 3 months into two arms: ticagrelor plus placebo and ticagrelor plus aspirin. The primary endpoint of interest, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, occurred less frequently in the experimental arm (HR 0.56; 95% CI [0.45–0.68]; p<0.001), whereas the secondary endpoint of ischemic events was similar between the two arms (HR 0.99; 95% CI [0.78–1.25]). Transition from dual antiplatelet therapy consisting of ticagrelor plus aspirin to ticagrelor-based monotherapy in high-risk patients at 3 months after percutaneous coronary intervention resulted in a lower risk of bleeding events without an increase in risk of death, MI, or stroke.


2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.


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