Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: a pre-specified exploratory analysis from the TROPICAL-ACS trial

2019 ◽  
Vol 40 (24) ◽  
pp. 1942-1951 ◽  
Author(s):  
Dániel Aradi ◽  
Lisa Gross ◽  
Dietmar Trenk ◽  
Tobias Geisler ◽  
Béla Merkely ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Outcomes ◽  
Independent Predictor ◽  
Platelet Reactivity ◽  
Academic Research ◽  
Study Groups ◽  
Cardiovascular Death ◽  
Control Group ◽  
Coronary Syndrome ◽  
Increased Risk

Abstract Aims The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. Methods and results Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2–5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57–1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47–1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01–4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18–2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. Conclusion Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel.

A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study

Cardiology ◽  
2017 ◽  
Vol 138 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Cai De Jin ◽  
Moo Hyun Kim ◽  
Junghee Bang ◽  
Victor Serebruany
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Academic Research ◽  
P2y12 Receptor ◽  
Drug Eluting Stent ◽  
Platelet Response ◽  
Open Label ◽  
Korean Patients ◽  
Coronary Syndrome ◽  
Half Dose

Background: The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. Design: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). Conclusion: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.

CHECKING THE ASSOCIATION OF FIVE SNP WITH UNVALVED ATRIAL FIBRILLATION IN PATIENTS WITH ACUTE CORONARY SYNDROME

2021 ◽  
pp. 42-52
Author(s):  
Lozhkina N.G. ◽  
Gurazheva A.A. ◽  
Maksimov V.N.
Keyword(s):  
Atrial Fibrillation ◽  
Acute Coronary Syndrome ◽  
Acute Coronary Syndrome Patient ◽  
Study Groups ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Male Patients ◽  
European Society Of Cardiology

Вackground. It is known that 5–21% of patients with acute coronary syndrome (ACS) develop atrial fibrillation (AF), which entails an increased risk of recurrence of myocardial infarction, heart failure, and increased mortality. The genetic predisposition to AF has been actively studied in recent years, but the data on the association of certain single nucleotide polymorphisms (SNPs) in the development of AF are contradictory, which determines the relevance of this study. Purpose of the study. To study five SNPs for associations with the development of non-valvular atrial fibrillation in patients with acute coronary syndrome Patient Characterization and Research Methods. The study included female and male patients not younger than 18 years old with ACS and AF (n = 133) and ACS without AF (n = 133) ACS was diagnosed according to the criteria of the European Society of Cardiology (2015; 2017). The study was approved by the Ethics Committee (Minutes No. 102 dated November 24, 2017). The observation period was 12 months. In addition to the standard examination, all patients underwent a SNP study: rs6795970 (Scn10a), rs2200733 (4th stage), rs11556924 (ZC3HC1), rs599839 (PSRC1), rs10824026 (10th stage). Statistical analysis was performed using Statistica 12.1 StatSoft. Results. The results of the rs599839 study showed that the GG genotype was significantly less common in the ACS + AF group compared to the ACS group without AF (OR 0.11 CI 95% 0.01; 0.86 p = 0.0163). A reliable connection was lost when divided by sex and by age (older and younger than 55). Allele G rs599839 significantly correlates with AF (p = 0.0043; OR 1.56). The T allele rs11556924 is highly reliably associated with a predisposition to atrial fibrillation (p = 0.0043; OR 1.93). Genotype GG rs10824026 is conditionally protective in terms of the risk of AF in patients with ACS. For rs6795970 (p = 0.290) and rs2200733 (p = 0.30), there were no statistically significant differences between the study groups. Conclusion. The study verified the association of rs6795970 (Scn10a), rs2200733, rs11556924, rs599839, rs10824026 with AF associated with ACS. The genotypes GG rs599839 and GG rs10824026 were found to be conditionally protective in relation to the risk of AF in patients with ACS.

Genotype-Phenotype Association and Impact on Outcomes following Guided De-Escalation of Anti-Platelet Treatment in Acute Coronary Syndrome Patients: The TROPICAL-ACS Genotyping Substudy

2018 ◽  
Vol 118 (09) ◽  
pp. 1656-1667 ◽  
Author(s):  
Lisa Gross ◽  
Dietmar Trenk ◽  
Claudius Jacobshagen ◽  
Anne Krieg ◽  
Meinrad Gawaz ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Control Group ◽  
Carrier Status ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Coronary Syndrome ◽  
Alternative Treatment Strategy

Background Phenotype-guided de-escalation (PGDE) of P2Y12-inhibitor treatment with an early switch from prasugrel to clopidogrel was identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Genotyping Substudy aimed to investigate whether CYP2C19 genotypes correlate with on-treatment platelet reactivity (PR) in ACS patients treated with clopidogrel or prasugrel and thus might be useful for guidance of early de-escalation of anti-platelet treatment. Methods and Results A total of 603 ACS consecutive patients were enrolled in four centres (23.1% of the overall TROPICAL-ACS population). Rapid genotyping (Spartan RX) for CYP2C19*2, *3 and *17 alleles was performed. Associations between PR and the primary and secondary endpoints of the TROPICAL-ACS trial and CYP2C19*2 and CYP2C19*17 carrier status were evaluated.For the PGDE group, the on-clopidogrel PR significantly differed across CYP2C19*2 (p < 0.001) and CYP2C19*17 genotypes (p = 0.05). Control group patients were not related (p = 0.90, p = 0.74) to on-prasugrel PR. For high PR versus non-high PR patients within the PGDE group, significant differences were observed for the rate of CYP2C19*2 allele carriers (43% vs. 28%, p = 0.007). Conclusion CYP2C19*2 and CYP2C19*17 carrier status correlates with PR in ACS patients treated with clopidogrel and thus might be useful for pre-selecting patients who will and who may not be suitable for PGDE of anti-platelet treatment. Regarding phenotype-guided treatment, we did not observe added benefit of genotyping to predict ischaemic and bleeding risk in patients who underwent a PGDE approach. Clinical Trial Registration URL: https//www.clinicaltrials.gov. Unique Identifier: NCT: 01959451.

scholarly journals Impact of new P2Y12 blockers on platelet reactivity and clinical outcomes after acute coronary syndrome: Insight from a large single center registry

2014 ◽  
Vol 4 ◽  
pp. 188-192 ◽  
Author(s):  
Pierre Deharo ◽  
Marie Loosveld ◽  
Guillaume Bonnet ◽  
Mathieu Pankert ◽  
Jacques Quilici ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Outcomes ◽  
Platelet Reactivity ◽  
Single Center ◽  
Coronary Syndrome

scholarly journals Role of ST2 in Non–ST-Elevation Acute Coronary Syndrome in the MERLIN-TIMI 36 Trial

2012 ◽  
Vol 58 (1) ◽  
pp. 257-266 ◽  
Author(s):  
Payal Kohli ◽  
Marc P Bonaca ◽  
Rahul Kakkar ◽  
Anastacia Y Kudinova ◽  
Benjamin M Scirica ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Controlled Trial ◽  
Cardiovascular Death ◽  
Acute Injury ◽  
Metabolic Efficiency ◽  
Coronary Syndrome ◽  
Independent Events ◽  
Increased Risk ◽  
St Elevation ◽  
Elevation Acute Coronary Syndrome

Abstract OBJECTIVE We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial. BACKGROUND Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS. METHODS We measured ST2 with a high-sensitivity assay in all available baseline samples (N = 4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non–ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee. RESULTS Patients with ST2 concentrations in the top quartile (&gt;35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P &lt; 0.0001) and 1 year (12.2% vs 5.2%, P &lt; 0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15–3.13 at 30 days, P = 0.012; 1.51, 95% CI 1.15–1.98 at 1 year, P = 0.003), with a significant integrated discrimination improvement (P &lt; 0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction = 0.15). CONCLUSIONS ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.

scholarly journals Clinical outcomes of patients with acute coronary syndrome and moderate or severe chronic anaemia undergoing coronary angiography or intervention

2017 ◽  
Vol 7 (7) ◽  
pp. 646-651 ◽  
Author(s):  
Lea Ohana-Sarna-Cahan ◽  
Shaul Atar
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Coronary Angiography ◽  
Haemoglobin Level ◽  
Clinical Outcomes ◽  
Coronary Intervention ◽  
Severe Anaemia ◽  
Control Group ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Background: There are limited data on the impact of chronic moderate or severe anaemia on the clinical outcomes of patients with acute coronary syndrome undergoing coronary angiography or percutaneous coronary intervention. Methods: We retrospectively compared two groups of consecutive patients with acute coronary syndrome according to their haemoglobin level on admission. The research group ( n=89) had a haemoglobin level of 10.9 g/dl or less and a control group ( n=79) of age-matched patients had a haemoglobin level greater than 10.9 g/dl. We studied drug therapy before, during and after intervention, and performed 1-year follow-up of bleeding complications according to the Bleeding Academic Research Consortium criteria, all-cause mortality and re-infarction, as well as haemoglobin level on discharge, 6 and 12 months after admission. Results: Compared to controls, a haemoglobin level less than 10.9 g\dl on admission is associated with a higher rate of major bleeding: 26 patients (32%) versus none in the control group ( P<0.001); and the use of packed red blood cell (RBC) transfusion: nine patients (11.7%) versus none in the control group ( P=0.003) within the first 6 months post-catheterisation. However, the re-infarction rate and mortality were similar in the study and control groups: 9.2% versus 9.7% ( P=0.915) and 12.6% versus 8.9% ( P=0.434), accordingly. Conclusions: Chronic moderate or severe anaemia in patients with acute coronary syndrome undergoing coronary angiography or percutaneous coronary intervention is associated with a substantially increased risk of bleeding in the first 6 months. However, rates of mortality and re-infarction were similar.

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