scholarly journals Downstream or upstream administration of P2Y12 receptor blockers in non-ST elevated acute coronary syndromes: study protocol for a randomized controlled trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Giuseppe Tarantini ◽  
Marco Mojoli ◽  
Ferdinando Varbella ◽  
Roberto Caporale ◽  
Stefano Rigattieri ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Randomized Study ◽  
Academic Research ◽  
Optimal Timing ◽  
Coronary Anatomy ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Safety Endpoint ◽  
Research Consortium

Abstract Background The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors—ticagrelor and prasugrel—currently recommended by the guidelines. Study design DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. Conclusions The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. Trial registration ClinicalTrials.gov NCT02618837. Registered on 1 December 2015.

scholarly journals Clopidogrel or ticagrelor alongside dabigatran in acute coronary syndrome and indication for NOAC: a study rationale

2021 ◽  
Author(s):  
Jasper Luijkx ◽  
Patty Winkler ◽  
Arnoud van 't Hof
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Controlled Trial ◽  
Oral Anticoagulants ◽  
Academic Research ◽  
Coronary Intervention ◽  
Open Label ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

The combination of oral anticoagulants with platelet inhibitors has been widely investigated in patients with coronary stenting and concomitant atrial fibrillation. In these patients, default therapy after percutaneous coronary intervention in acute coronary syndrome is clopidogrel plus non–vitamin K antagonist oral anticoagulant, omitting aspirin. However, in view of the high thromboembolic risk associated with acute coronary syndrome and the number of poor metabolizers for clopidogrel, investigation of alternative P2Y12-inhibitors is mandatory. This prospective, multicenter, open-label, registry-based, randomized, controlled trial aims to show the non-inferiority of dabigatran plus ticagrelor versus dabigatran plus clopidogrel in patients on chronic anticoagulants who undergo percutaneous coronary intervention in acute coronary syndrome. The primary end point is major bleeding as defined by the Bleeding Academic Research Consortium bleeding definition. Trial registration number: NL75644.096.21

scholarly journals Switching Ticagrelor to 600 mg or 300 mg Clopidogrel Loading Bridge in Patients with Unstable Angina

2021 ◽  
Vol 10 (11) ◽  
pp. 2463
Author(s):  
Sinem Cakal ◽  
Beytullah Cakal ◽  
Zafer Güven ◽  
Aydın Rodi Tosu ◽  
Muhsin Kalyoncuoglu ◽  
...  
Keyword(s):  
Unstable Angina ◽  
Stent Thrombosis ◽  
Ad Hoc ◽  
Antiplatelet Agent ◽  
Academic Research ◽  
Coronary Intervention ◽  
Coronary Syndrome ◽  
Significant Difference ◽  
Safety Endpoint ◽  
Research Consortium

Ticagrelor is believed to be a more potent and faster antiplatelet agent compared with clopidogrel and may result in lower ischemic outcomes in patients with acute coronary syndrome. However, the best strategy of switching from ticagrelor to clopidogrel is unclear. Current guidelines advocate clopidogrel bridging with a 600 mg loading dose (LD). This study aimed to compare the safety and feasibility of switching protocols from ticagrelor to clopidogrel 600 mg or 300 mg LD in patients with unstable angina pectoris (USAP). One hundred and eighty patients with USAP undergoing adhoc percutaneous coronary intervention (PCI) received preprocedural ticagrelor 180 mg/daily. The decision to switch antiplatelet therapy to clopidogrel with either 300 mg LD or 600 mg LD at 12 h was left to the discretion of the treating physician. The primary outcome was a composite of an efficacy endpoint major adverse cardiac and cerebrovascular events (MACCEs) and a safety endpoint Bleeding Academic Research Consortium scale (BARC) (≥1). There were no differences in our composite clinical endpoint of MACCE between the two strategies, with one event occurring in each group. One patient in each group had myocardial infarction due to stent thrombosis, and the patient in the 300 mg switching group died due to stent thrombosis. No difference between the two arms was observed in terms of BARC bleeding criteria. This study showed that among USAP patients undergoing PCI, switching to clopidogrel with 300 mg LD showed no significant difference compared to 600 mg clopidogrel LD. Ticagrelor LD in ad hoc PCI and de-escalation to clopidogrel with 300 mg LD could translate to lower costs for patients with USAP without compromising safety and efficacy.

Optimal Timing of P2Y12 Inhibitor Loading in Patients Undergoing PCI: A Meta-Analysis

2019 ◽  
Vol 119 (06) ◽  
pp. 1000-1020 ◽  
Author(s):  
Anna Komosa ◽  
Maciej Lesiak ◽  
Zbigniew Krasiński ◽  
Marek Grygier ◽  
Andrzej Siniawski ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Bleeding Complications ◽  
Major Adverse Cardiovascular Events ◽  
Optimal Timing ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
St Elevation

Background and Aim The timing of P2Y12 inhibitor loading in patients undergoing percutaneous coronary intervention (PCI) is a matter of debate. The aim of our study was to compare the efficacy and safety of oral P2Y12 inhibitors: clopidogrel, ticagrelor and prasugrel administered at two different time points in relation to PCI: early (> 2 hours pre-PCI) versus late (< 2 hours pre-PCI or post-PCI). Methods This is a systematic review and meta-analysis. Randomized controlled trials and non-randomized studies were included. Outcomes evaluated were combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), target vessel revascularization, death and bleeding complications. Summary estimates of the relative risks with therapy were calculated. Results Twenty-three studies met the selection criteria and included 60,907 patients. Early P2Y12 inhibitor loading was associated with a 22% relative risk reduction (RRR) of MACE (95% confidence interval [CI] = 0.68–0.89; p < 0.001). Early clopidogrel loading was associated with a 25% RRR of MACE (95% CI = 0.65–0.85; p < 0.001), a 30% RRR of MI (95% CI = 0.6–0.82; p < 0.0001) and 25% RRR of death (95% CI = 0.64–0.87; p = 0.0002), without an impact on major bleedings. In ST-elevation myocardial infarction as well as non-ST elevation acute coronary syndrome (NSTE-ACS), early clopidogrel loading resulted in 35 and 22% RRR in 30 days MACE (p < 0.001), respectively, with no impact in elective PCI. Whereas early loading with prasugrel and ticagrelor did not improve ischaemic outcomes, prasugrel administered early increased bleeding risks in NSTE-ACS. Conclusion Early clopidogrel loading is associated with a better efficacy and similar safety, whereas timing of ticagrelor or prasugrel loading had no effects on ischaemic events.

scholarly journals EARLY PRESCRIPTION OF PLATELET P2Y12 RECEPTOR INHIBITORS TO PATIENTS WITH ACUTE CORONARY SYNDROME: A BENEFIT OR A HARM?

2018 ◽  
pp. 76-86
Author(s):  
Roman M. Shakhnovich
Keyword(s):  
Acute Coronary Syndrome ◽  
Coronary Angiography ◽  
Secondary Prevention ◽  
Randomized Trials ◽  
P2y12 Receptor ◽  
Coronary Anatomy ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Main Component

Double antiplatelet therapy, which includes aspirin and platelet P2Y12 receptor inhibitors (hereinafter P2Y12 inhibitor) is the main component of treatment and secondary prevention after ACS. In recent years, the issue of determining whether it is expedient for P2Y12 inhibitors to be early prescribed to patients with ACS – prior to coronary angiography, when coronary anatomy is unknown – has been widely debated. The review provides comprehensive up-to-date information on this topic based on data from randomized trials, registers, and official clinical guidelines.

Assessing bleeding in acute coronary syndrome using the Bleeding Academic Research Consortium definition

2019 ◽  
Vol 20 (12) ◽  
pp. 818-824
Author(s):  
Federico Fortuni ◽  
Gabriele Crimi ◽  
Nuccia Morici ◽  
Giuseppe De Luca ◽  
Luca Paolo Alberti ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Academic Research ◽  
Coronary Syndrome ◽  
Research Consortium

Abstract 16898: Clinical Implementation of Pharmacogenomics Testing to Guide P2Y12 Inhibitor Use in Older Adults With Acute Coronary Syndrome: Insights From a Prospective Pilot Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sagune Sakya ◽  
CHRISTOPHER J Regan ◽  
Lionel Picot-Vierra ◽  
Ralph J Riello ◽  
Lydia Tran ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Pilot Study ◽  
Health System ◽  
Acceptance Rate ◽  
Clinical Implementation ◽  
Implementation Barriers ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome

Introduction: CYP2C19 testing is a known pharmacogenomics application to identify patients who can activate clopidogrel. Evidence-based guidelines now support second generation P2Y12 inhibitors over clopidogrel for the management of acute coronary syndrome (ACS). However, continued broad use of clopidogrel within our health-system indicated the potential value of pharmacogenomic testing to guide P2Y12 inhibitor prescribing. This study aimed to evaluate the clinical application of pharmacogenomic testing within a cardiovascular population and identify optimizations to the implementation process. Methods: This was a prospective, descriptive cohort pilot study at a large academic health-system. A high-impact pilot population included patients 65 years and older admitted for ACS who underwent percutaneous coronary intervention (PCI). Pharmacists identified eligible patients and made genomic-guided P2Y12 inhibitor recommendations for each patient. Surrogate markers of clinical impact included clopidogrel prescribing rates and quantification of active medication-gene interactions. Process indicators included acceptance rate of recommendations. Results: A total of 151 patients were included. At the time of result return, 46% of patients were on clopidogrel. Of these patients, 27% were identified as poor or intermediate metabolizers and were indicated for a change in therapy. The acceptance rate of genomic-guided recommendations was 42%. Identified barriers to uptake included result turnaround time limiting application of findings and unclear responsibility of follow-up. Conclusions: Results from this real-world study support implementation of CYP2C19 testing to guide P2Y12 inhibitor use. Identifying candidates for clopidogrel use through testing has potential clinical and cost benefits, but further studies are needed. Process optimizations are required to address implementation barriers and increase follow-up on actionable results.

scholarly journals 817 Potent P2Y12 inhibitors in elderly population, insigth from praise registry

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Edoardo Elia ◽  
Fabrizio D’Ascenzo ◽  
Susanna Breviario ◽  
Francesco Bruno ◽  
Giorgio Marengo ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Academic Research ◽  
Coronary Intervention ◽  
Cardiac Events ◽  
Safety And Efficacy ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Neutral Effect

Abstract Background The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly patients with acute coronary syndrome (ACS) remains unclear. Methods All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3-5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones. Results 4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16±3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63-1.52, p=0.94 and HR 0.38; 0.14-1.04, p=0,06), reduced risk of MACE and MI (HR 0.82; 0.23-0.91, p=0.03 and HR 0.43; 0.14-0.89, p=0.04) and increased risk of BARC 3-5 bleeding (HR 2.14; 1.19-3.85, p=0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22-0.95, p=0.04 and HR 2.36; 1.02-5.52, p=0.04, all 95%CI) with neutral effect on NACE and MACE. Conclusions In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older. 817 Figure 1

scholarly journals Outcomes and Hemodynamic Performances of Transcatheter Aortic Valve Replacement With Two Generations of Self-expanding Transcatheter Aortic Valves

2021 ◽  
Author(s):  
Chia-Cheng Kuo ◽  
Hsiao-Huang Chang ◽  
Hsin-Bang Leu ◽  
I-Ming Chen ◽  
Po-Lin Chen ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Clinical Performance ◽  
Academic Research ◽  
Conversion To Open Surgery ◽  
Transcatheter Aortic Valve ◽  
Two Generations ◽  
Safety Endpoint ◽  
Transcatheter Valve ◽  
Research Consortium ◽  
New Generation

Abstract The aim of this study was to investigate the hemodynamic and clinical performance of the Evolut R compared with its direct predecessor, CoreValve, in Taiwanese population. This study included all consecutive patients who underwent TAVR with either the CoreValve or Evolut R between March 2013 to December 2020. Thirty-day Valve Academic Research Consortium-2 (VARC-2)-defined outcomes and hemodynamic performances were investigated. There were no significant differences in baseline demographic characteristics between patients receiving CoreValve (n= 117) or Evolut R (n=117). Aortic valve-in-valve procedures for failed surgical bioprosthesis and procedures under conscious sedation were performed significantly more often with Evolut R. Pre-dilatation was performed significantly more often and contrast media volume was significantly higher with CoreValve. Stroke (0% vs 4.3%, p = 0.024) and the need for emergent conversion to open surgery (0% vs 5.1%, P = 0.012) were significantly lower in Evolut R than CoreValve recipients. Evolut R significantly reduce 30-day composite safety endpoint (4.3% vs 15.4%, p = 0.004). In conclusion, advancements in transcatheter valve technologies have resulted in improved outcomes for patients undergoing TAVR with self-expanding valves. With new-generation Evolut R, device success was high and significantly reduced 30-day composite safety endpoint after TAVR compared with CoreValve.

scholarly journals Risk of Major Bleeding With Potent Antiplatelet Agents After an Acute Coronary Event: A Comparison of Ticagrelor and Clopidogrel in 5116 Consecutive Patients in Clinical Practice

2021 ◽  
Author(s):  
Liam Mullen ◽  
Mohammed N. Meah ◽  
Ahmed Elamin ◽  
Suneil Aggarwal ◽  
Adeel Shahzad ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Practice ◽  
Coronary Artery ◽  
Major Bleeding ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Academic Research ◽  
Artery Bypass Graft ◽  
Coronary Syndrome ◽  
Research Consortium

Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all‐cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3–5, hazard ratio [HR], 1.23; 95% CI, 0.90–1.68; P =0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98–1.74; P =0.07) except in the non‐coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3–5, adjusted HR, 1.58; 95% CI, 1.09–2.31; P =0.017; and PLATO major HR, 1.67; 95% CI, 1.18–2.37; P =0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87–1.64; P =0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76–1.10; P =0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52–1.32; P =0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02484924.

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