255Impact of the type of acute coronary syndrome on the pharmocodynamic response to P2Y12 inhibitors in the acute and maintenance phase of therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Lugo Gavidia ◽  
D Vivas ◽  
J M De La Hera ◽  
A Tello-Montoliu ◽  
A L Marcano ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Maintenance Phase ◽  
Platelet Inhibition ◽  
Clinical Indication ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
P2y12 Antagonists ◽  
St Elevation ◽  
The Impact

Abstract Background The presence of an acute coronary syndrome (ACS) is per se a predictor of reduced responsiveness to clopidogrel; in particular, patients with ST-elevation myocardial infarction (STEMI) have impaired clopidogrel-induced platelet inhibition than those with other forms of ACS. However, the impact of the type of ACS on the pharmocodynamic efficacy of more potent P2Y12 antagonists such as prasugrel or ticagrelor has not been fully elucidated to date. Purpose To assess the impact of the type of ACS on platelet inhibition mediated by P2Y12 receptor antagonists in the acute and the maintenance phase of therapy in a contemporary cohort of ACS patients undergoing percutaneous coronary intervention (PCI). Methods Substudy of a prospective, national, multicentre, pharmacodynamic registry conducted in a population of ACS patients undergoing PCI and treated with dual antiplatelet therapy including aspirin and a P2Y12 inhibitor as per clinical indication. Patients were classified according to the ACS diagnosis into groups: a) STEMI, b) non-ST-elevation ACS (NSTEACS), c) unstable angina (UA), and d) other (excluded from the present analysis). Platelet function tests (PFT) were performed at day 1 and day 30 (±5) after PCI and included: 1) VerifyNow P2Y12 assay, expressed as P2Y12 reaction units (PRUs); 2) Vasodilator-stimulated phosphoprotein (VASP) assay; and 3) Multiple electrode aggregometry (MEA). Results A total of 965 patients (372 with STEMI, 395 with NSTEACS and 198 with UA) were included in the present substudy. At day 1, the proportions of patients with each type of ACS according to the P2Y12 inhibitor received were: 1) clopidogrel (n=317): STEMI 35.0%, NSTEACS 34.4% and UA 30.6%; 2) prasugrel (n=192): STEMI 70.3%, NSTEACS 17.7% and UA 12.0%; 3) ticagrelor (n=456): STEMI 27.6%, NSTEACS 55.3% and UA 17.1%. A statistically significant reduced platelet inhibition, measured with the VerifyNow system, was observed in STEMI patients compared with the other forms of ACS in patients receiving clopidogrel (STEMI: 217.3±8.1, NSTEACS: 157.1±7.9 and UA: 164.9±8.6 PRUs; p for STEMI vs. NSTEACS <0.001 and p for STEMI vs. UA <0.001) and ticagrelor (STEMI: 57.7±3.8, NSTEACS: 45.2.1±2.6 and UA: 40.6±4.9 PRUs; p for STEMI vs. NSTEACS 0.008 and p for STEMI vs. UA 0.007), while a numerical trend towards greater platelet reactivity in STEMI compared to UA was observed in subjects receiving prasugrel (Figure). Remarkably, at day 30, no significant differences on platelet inhibition were observed according to the ACS type with any of the P2Y12 inhibitors. Similar results were observed with MEA and VASP assays. PD response according to the ACS type Conclusions Patients presenting with STEMI have impaired platelet inhibition mediated by P2Y12 antagonists compared to other types of ACS during the acute phase of therapy, whereas no difference is observed during the maintenance phase of treatment. Acknowledgement/Funding Funded by Instituto de Salud Carlos III through the project PI13/01012 (co-funded by European Regional Development Fund. ERDF, a way to build Europe)

scholarly journals Reversible P2Y12 inhibitor versus irreversible P2Y12 inhibitor in ACS patients undergoing PCI (the acute coronary syndrome israeli survey (ACSIS)

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Eliaz ◽  
B Mengesha ◽  
T Ovdat ◽  
Z Iakobishvili ◽  
D Hasdai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Coronary Syndrome ◽  
Real Life ◽  
Coronary Intervention ◽  
Complication Rates ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Direct Head ◽  
St Elevation

Abstract Introduction Based on data from randomized controlled trials, both American and European guidelines recommend treating acute coronary syndrome (ACS) patients with second generation P2Y12 inhibitors.1,2 Direct head-to-head comparison of these agents was scarce until the recent publication of the ISAR-REACT-5 study which demonstrated the superiority of the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) over the reversible P2Y12 inhibitor in terms of 1-year composite of death, myocardial infarction (MI), and stroke.3,4,5 Given the unexpected outcomes of this trial, we sought to perform a comparison of ticagrelor and prasugrel in real-life ACS patients. Purpose To compare the outcomes of ACS (acute coronary syndrome) patients undergoing in-hospital PCI (percutaneous coronary intervention) treated with the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) versus the reversible P2Y12 inhibitor. Methods ACSIS (Acute Coronary Syndrome in Israel) is a national ACS snapshot survey conducted in all 25 cardiology departments in Israel since 2000 over a two-month period, every two to three years. Both the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) and the reversible P2Y12 inhibitor were commercially introduced in Israel in 2010. We therefore considered patients enrolled in ACSIS surveys 2010–2018 for the present analysis. Results Among 7,233 patients enrolled to the ACSIS (Acute Coronary Syndrome in Israel) registry between 2010 and 2018, we identified 1133 eligible patients treated with the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) and 825 with the reversible P2Y12 inhibitor. In hospital complication rates, including rates of stent thrombosis, were roughly similar between groups. Compared to the reversible P2Y12 inhibitor, the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) was associated with lower 1-year death in ST-elevation myocardial infarction (STEMI) patient compared to non-ST-elevation ACS (NSTE-ACS) patients (p for interaction 0.03). In propensity score matched STEMI patients (502 receiving the Irreversible thienopyridine type P2Y12 inhibitor (prodrug), 251 the reversible P2Y12 inhibitor) 30-day re-hospitalization rate (p&lt;0.05), 30-day MACE (the composite of death, MI, stroke, urgent revascularization; p=0.006), and 1-year mortality rates (p=0.08) were higher in the the reversible P2Y12 inhibitor group compared to the the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) group; In NSTE-ACS patients, outcomes were not impacted by drug choice. Conclusion The Irreversible thienopyridine type P2Y12 inhibitor (prodrug) was more effective than the reversible P2Y12 inhibitor in STEMI patients, but not in NSTE-ACS patients. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): the Israeli working group on acute cardiac care of the Israel heart society

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

2020 ◽  
Vol 41 (33) ◽  
pp. 3144-3152 ◽  
Author(s):  
Boris Schnorbus ◽  
Andreas Daiber ◽  
Kerstin Jurk ◽  
Silke Warnke ◽  
Jochem Koenig ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Endothelial Function ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Clinical Parameter ◽  
Mean Difference ◽  
Low Flow ◽  
Flow Mediated Dilation ◽  
Coronary Syndrome ◽  
The Impact

Abstract Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P &lt; 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68–3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31–2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI −0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusion As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73

Prasugrel compared with high-dose clopidogrel in acute coronary syndrome

2010 ◽  
Vol 103 (01) ◽  
pp. 213-223 ◽  
Author(s):  
Georgios Sideris ◽  
Remy Cohen ◽  
Catherine Meuleman ◽  
Claire Bal dit Sollier ◽  
Olivier Barthélémy ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Poor Response ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
High Dose ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
St Elevation ◽  
To Receive

SummaryCompared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 μM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

scholarly journals Impact of smoking habit on platelet reactivity in a cohort of patients admitted due to an acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.C Gomez Polo ◽  
D Vivas Balcones ◽  
A.L Marcano Fernandez ◽  
J Playan Escribano ◽  
L.M Lugo Gavidia ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Smoking Habit ◽  
Tertiary Care ◽  
Funding Source ◽  
P2y12 Inhibitors ◽  
Lower Response ◽  
Coronary Syndrome ◽  
The Impact

Abstract Background Several pharmacodynamic studies have shown the impact of smoking habit on platelet reactivity; with a reduction on platelet aggregation. Wether this inhibition in platelet reactivity is due to tobacco effects in platelet signaling pathways or due to a pharmacodynamic interaction with antiplatelet therapies is not well stablished. Purpose Our aim was to study the influence of smoking habit in platelet reactivity and in the response to P2Y12 inhibitors. Methods Patients admitted in four tertiary care hospitals due to an acute coronary syndrome that undergone percutaneous coronary intervention (PCI) were consecutively and prospectively recruited. All the patients received dual antiplatelet therapy with aspirin and a P2Y12 inhibitor following current European Guidelines. Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y12, VASP (Vasodilator-stimulated phosphoprotein) y MEA (Multiple electrode aggregometry). Results A total of 1000 patients were enrolled, of whom 12 had to be excluded due to inaccurate processing of blood samples. 372 patients (37,6%) had smoking habit. Non-smoking patients showed higher prevalence of high blood pressure [423 (68.7%) vs 196 (52.7%)] and diabetes mellitus [213 (34.6%) vs 81 (21.8%)]. Smoking patients were younger [57.3 (9,6) years old vs 68.4 (11.1)], with higher incidence of acute coronary syndrome with ST segment elevation [184 patients (49,5%) vs 241 (39.1%), p&lt;0,001]. There were no differences in platelet function at day 1. When analysing platelet function 30 days post-PCI, a lower inhibition of platelet reactivity in non-smoking patients as compared with smoking patients was observed in those treated with clopidogrel, with higher prevalence of clopidogrel-resistance in non-smoking patients (VerifyNow, 51,2% prevalence of high platelet reactivity in non-smoking patients vs 34,9% 30 days after PCI, p=0,023). On the other hand, smoking patients that received ticagrelor did not show any differences. Patients with smoking habit treated with prasugrel showed a lower response of borderline statistical significance. Conclusion Smoking habit was associated with a lower response to prasugrel of borderline significance, and with higher response to clopidogrel, according with previous studies suggesting a pharmacodynamics interaction between tobacco use and P2Y12 inhibitors. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fondo de Investigaciones Sanitarias (FIS)

The impact of in-hospital P2Y12 inhibitor switch in patients with acute coronary syndrome

2018 ◽  
Vol 19 (8) ◽  
pp. 912-916 ◽  
Author(s):  
Deepakraj Gajanana ◽  
William S. Weintraub ◽  
Paul Kolm ◽  
Toby Rogers ◽  
Micaela Iantorno ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
P2y12 Inhibitor ◽  
Coronary Syndrome ◽  
The Impact

scholarly journals 2020 Asia Pacific Society of Cardiology Consensus Recommendations on the Use of P2Y12 Receptor Antagonists in the Asia-Pacific Region

2021 ◽  
Vol 16 ◽  
Author(s):  
Jack WC Tan ◽  
Derek P Chew ◽  
Muhamad Ali SK Abdul Kader ◽  
Junya Ako ◽  
Vinay K Bahl ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Asia Pacific ◽  
Current Evidence ◽  
Regional Studies ◽  
Pacific Region ◽  
Asia Pacific Region ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Asian Patients ◽  
St Elevation

The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.

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.

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