scholarly journals Vorapaxar

2013 ◽  
pp. 88-95
Author(s):  
Gianluca Airoldi ◽  
Mauro Campanini
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Dual Antiplatelet Therapy ◽  
Absolute Risk ◽  
Standard Of Care ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Human Platelets ◽  
P2y12 Receptor ◽  
Thrombin Inhibition

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.

Abstract 15510: Trials of Dual Antiplatelet Therapy Do Not Include Evidence-Based Strategies for Gastrointestinal Bleeding Prevention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jacob E Kurlander ◽  
Geoffrey Barnes ◽  
Devraj Sukul ◽  
Danielle Helminski ◽  
Alex Kokaly ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Standard Of Care ◽  
Coronary Intervention ◽  
Flow Diagram ◽  
Clinical Trial Registries ◽  
Study Protocols ◽  
Registration Number ◽  
Hemorrhagic Risk

Background: Proton pump inhibitors (PPIs) substantially reduce the risk of upper gastrointestinal bleeding (GIB) and are recommended for high-risk patients by professional cardiology societies but remain underused in clinical practice. By reducing hemorrhagic risk associated with dual antiplatelet therapy (DAPT), PPIs may affect the risk-benefit equation of varying durations of DAPT and should be considered in such clinical trials. We sought to determine the extent to which randomized controlled trials (RCTs) evaluating DAPT after percutaneous coronary intervention (PCI) provide guidance on the use of PPIs for GIB prevention. Methods: A previously completed systematic review was updated to identify all RCTs comparing varying durations of DAPT between June 1983 and October 2019. Primary publications, online supplements, clinical trial registries and additional publications linked to the trial registration number were reviewed for protocol information. Results: Of 21 included studies (n=58,625; Figure), none of the study protocols provided guidance on the use of PPIs by trial participants. One study stated that the decision to use PPIs was left to the discretion of the treating physician. Two studies specified that treating physicians could prescribe non-mandated medications concordant with standard of care but did not specifically mention PPIs. Only 5 studies reported rates of PPI use, which ranged from 25.6-69.1%. Conclusions: Trials of DAPT regimens did not provide guidance on the use of PPI gastroprotection, a guideline-supported strategy for prevention of bleeding from the GI tract, the most common site of bleeding in patients using DAPT. Guidance on and reporting of PPI use should be mandatory in future antithrombotic trials to enhance their safety and interpretability. Figure 1. PRISMA flow diagram

Supplemental Fibrinogen Restores Platelet Inhibitor-Induced Reduction in Thrombus Formation without Altering Platelet Function: An In Vitro Study

2020 ◽  
Vol 120 (11) ◽  
pp. 1548-1556
Author(s):  
Thomas Bärnthaler ◽  
Elisabeth Mahla ◽  
Gabor G. Toth ◽  
Rufina Schuligoi ◽  
Florian Prüller ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Function ◽  
Dual Antiplatelet Therapy ◽  
Thrombus Formation ◽  
In Vitro Study ◽  
Coronary Intervention ◽  
Calcium Flux ◽  
Major Surgery

Abstract Background For patients treated with dual antiplatelet therapy, standardized drug-specific 3-to-7 day cessation is recommended prior to major surgery to reach sufficient platelet function recovery. Here we investigated the hypothesis that supplemental fibrinogen might mitigate the inhibitory effects of antiplatelet therapy. Methods and Results To this end blood from healthy donors was treated in vitro with platelet inhibitors, and in vitro thrombus formation and platelet activation were assessed. Ticagrelor, acetylsalicylic acid, the combination of both, and tirofiban all markedly attenuated the formation of adherent thrombi, when whole blood was perfused through collagen-coated microchannels at physiological shear rates. Addition of fibrinogen restored in vitro thrombus formation in the presence of antiplatelet drugs and heparin. However, platelet activation, as investigated in assays of P-selectin expression and calcium flux, was not altered by fibrinogen supplementation. Most importantly, fibrinogen was able to restore in vitro thrombogenesis in patients on maintenance dual antiplatelet therapy after percutaneous coronary intervention. Conclusion Thus, our in vitro data support the notion that supplementation of fibrinogen influences the perioperative hemostasis in patients undergoing surgery during antiplatelet therapy by promoting thrombogenesis without significantly interfering with platelet activation.

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 ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
P2y12 Receptor ◽  
Efficacy And Safety ◽  
Receptor Antagonists

Abstract 15357: P2Y12 Inhibitor Monotherapy After Short-term Dual Antiplatelet Therapy in Patients Receiving Percutaneous Coronary Intervention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ahmad Naeem Lone ◽  
Safi U Khan
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Short Term ◽  
P2y12 Inhibitor ◽  
Percutaneous Coronary ◽  
New Strategy

Introduction: The safety and effectiveness of new strategy of de-escalating short-term dual antiplatelet therapy (DAPT) (≤ 3-month) followed by P2Y12 inhibitor monotherapy versus 12-month DAPT after percutaneous coronary intervention (PCI) is unclear. Hypothesis: Short-term DAPT followed by P2Y12 inhibitor therapy might be safer and equally effective compared with 12-month DAPT. Methods: Five randomized controlled trials (n=32,181) comparing P2Y12 inhibitor monotherapy with DAPT after PCI were selected from MEDLINE and EMBASE databases through June 2020. Meta-analysis was performed using random effects model. Results are reported as absolute risk differences (ARDs) with 95% confidence intervals (CIs). Results: Short-term DAPT followed by P2Y12 monotherapy was associated with lesser risk of major bleeding compared with 12-month DAPT (ARD, -0.73% [95% CI, -1.32%, -0.14%]). There were no differences between all-cause mortality (ARD, -0.22% [95% CI, -0.50%, 0.07%]), cardiovascular mortality (ARD, -0.24% [95% CI, -0.51%, 0.03%]), myocardial infarction (ARD, -0.13% [95%CI, -0.40%, 0.14%]), MACE (ARD, -0.25% [95% CI, -0.73%, 0.24%]) and stroke (ARD, 0.03% (95% CI, -0.22%, 0.29%]). These results were consistent across use of clopidogrel or ticagrelor. Conclusions: Short term DAPT followed by P2Y12 inhibitor monotherapy after PCI is safer and equally effective compared with 12-month DAPT.

TWILIGHT: A Randomized Trial of Ticagrelor Monotherapy Versus Ticagrelor Plus Aspirin Beginning at 3 Months in High-risk Patients Undergoing Percutaneous Coronary Intervention

2020 ◽  
Vol 14 ◽  
Author(s):  
Johny Nicolas ◽  
Usman Baber ◽  
Roxana Mehran
Keyword(s):  
Percutaneous Coronary Intervention ◽  
High Risk ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
High Risk Patients ◽  
Risk Of Death ◽  
Percutaneous Coronary ◽  
Risk Patients

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.

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