Prasugrel in the treatment of acute coronary syndrome

2020 ◽  
Author(s):  
Michael Spartalis ◽  
Eleni Tzatzaki ◽  
Eleftherios Spartalis ◽  
Stavroula A Paschou ◽  
Antonios Athanasiou ◽  
...  

Dual antiplatelet therapy is the mainstay therapy in patients with acute coronary syndrome. The combination of aspirin and a P2Y12 inhibitor in patients who receive a coronary stent reduces the rate of stent thrombosis and the rates of major adverse cardiovascular events. The newer P2Y12 inhibitors (prasugrel and ticagrelor) have better efficacy than clopidogrel. Prasugrel provides greater inhibition of platelet aggregation and has a rapid onset of action. Current acute coronary syndrome guidelines recommend the use of both newer P2Y12 inhibitors. However, emerging data have shown that prasugrel is more efficient than ticagrelor in reducing the incidence of nonfatal myocardial infarction, stroke or cardiovascular death, without increased risk of major bleeding.

2019 ◽  
Vol 40 (24) ◽  
pp. 1942-1951 ◽  
Author(s):  
Dániel Aradi ◽  
Lisa Gross ◽  
Dietmar Trenk ◽  
Tobias Geisler ◽  
Béla Merkely ◽  
...  

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.


2012 ◽  
Vol 58 (1) ◽  
pp. 257-266 ◽  
Author(s):  
Payal Kohli ◽  
Marc P Bonaca ◽  
Rahul Kakkar ◽  
Anastacia Y Kudinova ◽  
Benjamin M Scirica ◽  
...  

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 (>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 < 0.0001) and 1 year (12.2% vs 5.2%, P < 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 < 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.


2019 ◽  
Vol 27 (7) ◽  
pp. 696-705 ◽  
Author(s):  
Fabrizio D'Ascenzo ◽  
Maurizio Bertaina ◽  
Francesco Fioravanti ◽  
Federica Bongiovanni ◽  
Sergio Raposeiras-Roubin ◽  
...  

Introduction The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. Methods All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3–5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2–5 bleeding, cardiovascular death and stent thrombosis. Results A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2–5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3–5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. Conclusion In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk–benefit ratio for longer DAPT due to excess of bleedings.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sagune Sakya ◽  
CHRISTOPHER J Regan ◽  
Lionel Picot-Vierra ◽  
Ralph J Riello ◽  
Lydia Tran ◽  
...  

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.


2021 ◽  
Vol 10 (14) ◽  
pp. 3166
Author(s):  
Adrian Włodarczak ◽  
Magdalena Łanocha ◽  
Marek Szudrowicz ◽  
Mateusz Barycki ◽  
Alicja Gosiewska ◽  
...  

Background: Diabetes mellitus (DM) is one of the major risk factors contributing to Acute Coronary Syndromes (ACS) and is associated with an increased risk of adverse clinical outcomes following percutaneous coronary intervention (PCI), even when the second generation of drug-eluting stents (DES) is used. In order to overcome the disadvantages of permanent caging of a vessel with metallic DES, bioresorbable scaffold (BRS) technology has been recently developed. However, the prognosis of patients with DM and ACS treated with PCI via subsequent implantation of Magmaris (Biotronik, Berlin, Germany)—a novel magnesium-bioresorbable scaffold—is poorly investigated. Methods: A total of 193 consecutive subjects with non-ST elevation acute coronary syndrome (NSTE-ACS) who, from October 2016 to March 2020, received one or more Magmaris scaffolds were enrolled in this study. The diabetic group was compared with non-diabetic subjects. Results: There were no significant differences in the occurrence of primary endpoints (cardiovascular death, myocardial infarction, and in-stent thrombosis) and principal secondary endpoints (target-lesion failure, scaffold restenosis, death from any reason, and other cardiovascular events) between the two compared groups in a 1-year follow-up period. Conclusions: The early 1-year-outcome of magnesium bioresorbable scaffold (Magmaris) seems to be favorable and suggests that this novel BRS is safe and effective in subjects with NSTE-ACS and co-existing DM.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Stephen J. Nicholls ◽  
◽  
Gregory G. Schwartz ◽  
Kevin A. Buhr ◽  
Henry N. Ginsberg ◽  
...  

Abstract Background Patients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known. Methods The phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied. Results Patients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38–0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27–0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53–0.98], P = 0.04). Conclusion Apabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lijiao Yang ◽  
Nan Ye ◽  
Guoqin Wang ◽  
Weijing Bian ◽  
Fengbo Xu ◽  
...  

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in patients with chronic kidney disease (CKD) and acute coronary syndrome (ACS). This study aimed to explore the frequency and impact of AF on clinical outcomes in CKD patients with ACS. Methods CKD inpatients with ACS between November 2014 and December 2018 were included based on the improving care for cardiovascular disease in China-ACS (CCC-ACS) project. Included patients were divided into an AF group and a non-AF group according to the discharge diagnosis. Multivariable logistic regression was used to adjust for potential confounders. Results A total of 16,533 CKD patients with ACS were included. A total of 1418 (8.6%) patients had clinically recognized AF during hospitalization, 654 of whom had an eGFR of 45 to < 60 ml/min/1.73 m2, and 764 had an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2. Compared with the non-AF group, the AF group had a higher risk of in-hospital mortality [OR 1.250; 95% CI (1.001–1.560), P = 0.049] and major adverse cardiovascular events (MACEs) [OR 1.361; 95% CI (1.197–1.547), P < 0.001]. We also found that compared with patients with eGFR 45 to < 60 ml/min/1.73 m2, patients with eGFR < 45 ml/min/1.73 m2 had a 1.512-fold increased risk of mortality and a 1.435-fold increased risk of MACEs. Conclusions AF was a risk factor affecting the short-term prognosis of ACS patients in the CKD population. Furthermore, the lower the eGFR, the higher the risk of in-hospital mortality and MACEs in CKD patients with ACS. Trial registry: Clinicaltrial.gov, NCT02306616. Registered 29 November 2014, https://clinicaltrials.gov/ct2/show/NCT02306616?term=NCT02306616&draw=2&rank=1


2020 ◽  
Vol 24 (4 (96)) ◽  
pp. 157-161
Author(s):  
V. Tashchuk ◽  
O. Malinevska-Biliichuk ◽  
I. Makoviichuk ◽  
D. Onofreichuk ◽  
K. Zlonikova

The aim – to determine the peculiarities of duration and treatment of a patient with myocardial infarction, complicated by pulmonary artery thrombosis and oncopathology, to show the complexity of management of such a group of patients.Matherial and methods. A clinical examination of the patient with myocardial infarction, complicated by pulmonary artery thrombosis and oncopathology was conducted.Results. Oncopatients are diagnosed acute coronary syndrome with elevation of ST segment more frequently compared to other patients. Oncothrombosis risk is connected with hypercoagulation and thrombocytopenia, cardiotoxicity of antitumor treatment, prolonged immobilization and procoagulant activity of malignant neoplasms.Сonclusion. Acute coronary syndrome and pulmonary artery thrombosis demand comprehensive approach to treatment, this group of patients has an increased risk of cardiovascular death, multidisciplinary approach and comprehensive analysis of such patients promotes early detection of pathology and timely treatment and prevention. Effective treatment for oncopatients with venous thrombosis are direct oral anticoagulants that reduce the risk of recurrent thrombosis, but should be used with caution in patients who have increased risk of major bleeding, the only recommended ones are rivaroxaban and edoxaban, also low-molecular-weight heparins, which can be prescribed to patients with risk of bleeding, cancer and inflammatory diseases of the gastrointestinal tract.


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