Treatment Of Acute Coronary Syndrome Patients Research Articles

Population pharmacokinetic study and application of ticagrelor and AR-C124910XX after percutaneous coronary intervention in Chinese patients with acute coronary syndrome.

This study aimed to understand the pharmacokinetics of ticagrelor in Chinese patients with acute coronary syndrome (ACS), identify influencing factors, and inform ticagrelor treatment optimization. Data from 195 ACS patients, including 491 plasma ticagrelor concentration timepoints and clinical information, were analyzed using NONMEN for pharmacokinetic (PK) parameter factors. The model underwent internal validation with bootstrap methodology. The PK curve of ticagrelor was well delineated using a one disposition compartment model with first-order absorption rate constant, 0.67/h. When the direct bilirubin levels and white plasma cell counts increased, female patients showed decreased glomerular filtration rate, decreased ticagrelor clearance rate, and increased exposure. When the direct bilirubin levels increased and body weight and hemoglobin decreased, rs6787801 was GG compared with AA and GA, the ticagrelor metabolite clearance rate decreased and exposure increased. The study offers key insights into ticagrelor's dose-exposure relationship post-percutaneous coronary intervention in ACS patients, highlighting factors critical for personalized treatment strategies.

Type of thrombus, no reflow and outcomes of coronary intervention in ACS patients: OCT-guided study.

Thrombus is the main finding in most patients with acute coronary syndrome (ACS), the type of which potentially impacts the end result of the interventional procedure in terms of no reflow and edge dissection. Optical coherence tomography (OCT) is considered a precise intra-vascular tool to image thrombi and characterise its properties. We aimed to study the impact of thrombus type, as defined by OCT, on procedural outcome in ACS patients. In this retrospective study we enrolled 100 patients who were treated by percutaneous coronary intervention (PCI) with the guidance of OCT. We recorded demographic and clinical data of the whole studied cohort. Angiographic details and procedural data were noted. Baseline OCT study was performed before intervention and repeated post- intervention. Plaque characterisation was identified, and thrombi were defined as red or white thrombi. Acute angiographic outcome was defined with special emphasis on no reflow. Male patients and ST-elevation myocardial infarction (STEMI) patients more often had white thrombi (58.1% and 71.2%, respectively). Cases with red thrombi had longer pain duration, which was statistically significant. Edge dissection was more frequent with red thrombus, 44.7% versus 32.1% with white thrombus, but the difference is not statistically significant, while 17% of patients with white thrombi were complicated by no-reflow phenomenon versus only 4.3% in patients with red thrombi, and this difference was statistically significant. In conculsion, OCT-guided PCI is feasible and safe in ACS settings. OCT- guided intra-procedural differentiation of thrombus type is potentially beneficial in predicting acute procedural outcome.

Benefit and Harm of Extended Dual Antiplatelet Therapy After PCI in high-risk TWILIGHT-like patients with acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following PCI irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients. This study sought to investigate the benefits and risks of extended-term (>12-month) DAPT as compared with short-term DAPT in high-risk "TWILIGHT-like" ACS patients undergoing PCI. Methods All consecutive patients fulfilling the "TWILIGHT-like" criteria undergoing PCI from January 2013 to December 2013 were identified from the prospective Fuwai PCI Registry. High-risk "TWILIGHT-like" patients were defined by at least 1 clinical and 1 angiographic feature based on TWILIGHT trial selection criteria. The present analysis evaluated 4,875 high-risk "TWILIGHT-like" patients with ACS who were event-free at 12 months after PCI. The primary outcome was the composite of all-cause death, myocardial infarction (MI), or stroke at 30 months while BARC type 2, 3, or 5 bleeding was key secondary outcome. Results Extended DAPT compared with shorter DAPT reduced the composite outcome of all-cause death, MI, or stroke by 63% (1.5% vs. 3.8%; HRadj: 0.374, 95% CI: 0.256 to 0.548; HRmatched: 0.361, 95% CI: 0.221-0.590). The HR for cardiovascular death was 0.049 (0.007 to 0.362) and that for MI 0.45 (0.153 to 1.320) and definite/probable stent thrombosis 0.296 (0.080-1.095) in propensity-matched analyses. Rates of BARC type 2, 3, or 5 bleeding (0.9% vs. 1.3%; HRadj: 0.668 [0.379 to 1.178]; HRmatched: 0.721 [0.369-1.410]) did not differ significantly in patients treated with DAPT > 12-month or DAPT ≤ 12-month. The effect of long-term DAPT on primary and key secondary outcome across the proportion of ACS patients with 1-3, 4-5, or 6-9 risk factors showed a consistent manner (Pinteraction > 0.05). Conclusion Among high-risk "TWILIGHT-like" patients with ACS after PCI, long-term DAPT reduced ischemic events without increasing clinically meaningful bleeding events as compared with short-term DAPT, suggesting that extended DAPT might be considered in the treatment of ACS patients who present with a particularly higher risk for thrombotic complications. Abstract Figure.

A Cross-sectional Study of Atherogenic Index of Plasma and Angiographic Profile by Gensini Score in Patients of Acute Coronary Syndrome

Introduction: Coronary Artery Disease (CAD) is the leading cause of death worldwide. India has the highest burden of Acute Coronary Syndrome (ACS). Atherogenesis is a multifactorial process, abnormalities in lipoprotein metabolism especially elevated Low Density Lipoprotein Cholesterol (LDLc) remains one of most attributing key factor. Atherogenic Index of Plasma (AIP), can be calculated easily from the formula AIP=Log 10 Triglyceride (TG)/High Density Lipoprotein Cholesterol (HDLc). The AIP is inversely proportional to the diameter of LDLc particles, which indirectly reflects Small Dense LDLc levels. AIP has been proposed as a marker for Cardiovascular (CV) risk. Aim: The study aimed to assess the correlation between AIP and the Angiographic Profile by Gensini Score (GS) in ACS patients and also to evaluate the relationship between AIP and in-hospital mortality of ACS patients. Materials and Methods: This study was a hospital based cross- sectional study. This study was done from November 2019 to October 2020 in the Department of Cardiology, Sriram Chandra Bhanja Medical College, Odisha, India. A total of 240 patients of ACS were included in the study. AIP was calculated from the lipid profile of all the ACS patients. Coronary Angiography was done in all of these patients. Correlation of the AIP was done with the severity of CAD according to Gensini scoring system. Chi-square test was used to compare continuous variables p<0.05 was considered significant. Spearman’s rho correlation was also used to compare AIP with GS. Statistical analysis was performed using Statistical Package for the Social Sciences, (SPSS) 26 (IBM). Results: Majority of the cases were males 194 (80.8%) and females were 46 (19.2%). The Spearmans rho coefficient between AIP and GS was 0.663. It was statistically significant (p<0.001). AIP had positive correlation (value) with severity of CAD by GS. In-hospital mortality was 5%. It was more in high risk AIP group with a p-value of 0.006 which was statistically significant. Conclusion: AIP shows positive correlation with the severity of CAD in terms of GS. High AIP is also associated with increased in-hospital mortality. AIP can be used in the treatment of ACS patients and is a suitable alternative to various costly biomarkers of CAD. Therefore, AIP can be advocated for routine measurement in clinical practice.

Comparison of Efficacy between Clopidogrel and Ticagrelor in Patients with Acute Coronary Syndrome after Interventional Treatment and Their Effects on IL-6

We aimed to compare the efficacy between clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) and their effects on IL-6. A retrospective analysis and collection of 200 ACS patients diagnosed by the Department of Cardiology, Affiliated Hospital of Qingdao University, Qingdao, China in 2016 were performed. Patients were randomly divided into clopidogrel group and ticagrelor group. Data of left ventricular ejection fraction and ACS clinical classification before PCI, PCI treatment, IL-6, platelet aggregation status, maximum platelet aggregation rate (MPAR), P2Y12 response unit (PRU) and adverse reaction of patients were collected. After PCI, patients were followed up for 1 year to compare the ischemia after treatment between clopidogrel group and tigravilol group. MPAR and PRU after PCI of clopidogrel group were significantly higher than those of ticagrelor group (P<0.05). The expression of IL-6 in two groups peaked at 1 day after PCI and then decreased. That of ticagrelor group was consistently lower than that of clopidogrel group (P<0.05). The incidence of ischemic events after treatment in clopidogrel group was significantly higher than that in ticagrelor group (P<0.001). Compared with clopidogrel, tigerrilol had more significant inhibition of platelet aggregation after PCI in ACS patients, and tigerrilol had better effect after interventional treatment in ACS patients. In addition, compared with clopidogrel, tegrel can significantly inhibit the expression of IL-6 in patients with ACS and better alleviate the inflammatory response after PCI.

P6412The AKR1D1*36 (rs1872930) allelic variant is independently associated with adverse cardiac events during Clopidogrel treatment

Abstract Background The treatment of acute coronary syndrome (ACS) includes dual antiplatelet therapy (DAPT) comprising of aspirin and a P2Y12 inhibitor; clopidogrel is usually the P2Y12 inhibitor of choice in patients with ACS. However, its efficacy has been questioned because of the relatively high incidence of Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) among ACS patients despite adherence to clopidogrel-DAPT. Several risk factors for MACCE following intervention in ACS patients have been described, among others, mutations in the CYP2C19 gene, a member of the cytochrome P450 (CYP450) network. The CYP2C19 enzyme is involved in the metabolism of clopidogrel Interindividual response variability to clopidogrel-DAPT and the increased risk for MACCE have been strongly linked to the CYP2C19*2 and CYP2C19*3 loss-of-function (LOF) allelic variants. Nonetheless, the known CYP2C19 polymorphisms fail to account for all adverse events related to clopidogrel insensitivity. Recent studies point to a putative role of the AKR1D1 gene as a trans-genetic regulator of the CYP450 network. The AKR1D1*36 (rs1872930) minor allelic variant was shown to augment hepatic CYP450 mRNA expression, consequently, increasing the CYP2C19 enzyme activity. To this end, we hypothesise that the AKR1D1*36 polymorphism contributes to the observed incidence of MACCE during clopidogrel antiplatelet therapy. Purpose To determine the association between the AKR1D1*36 (rs1872930) allele and MACCE in Acute Coronary Syndrome (ACS) patients on clopidogrel-DAPT Methods We evaluated 198 consecutive ACS patients indicated for coronary angiography from October to November 2010. We performed a 5-year retrospective medical record review and screened for AKR1D1 and CYP2C19 polymorphisms; 118 patients had a complete medical history and were included in the study. The study participants were prospectively followed for five years or until the first incidence of MACCE. The Median follow up time was 38.5 months (IQR 24–48 months) Results The median age of the cohort was 62.5 years (IQR 57–66), and 55% were females. Follow-up was complete, there were no mortality cases. ACS patients carrying the AKR1D1*36 had a significantly shorter event-free-survival compared to wildtype patients, Hazard Ratio = 2.193 [CI95% 1.091 to 4.406], p=0.0155 (Figure 1). Median time-to-event was 36 months. Evaluation of additional candidate risk predictors in a Cox Proportional Hazards Model confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 additional risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), a history of Myocardial Infarction, HR = 2.62; (95% CI, 1.48 to 4.64), at baseline and presence of the CYPC19*2 allele (HR = 2.33; 95% CI, 1.33 to 4.06). Figure 1. Time-to-Event curve of MACCE Conclusions The AKR1D1*36 (rs1872930) minor variant allele is independently associated with a higher risk for MACCE. Acknowledgement/Funding None

The soluble receptor for advanced glycation end-products (sRAGE) has a dual phase-dependent association with residual cardiovascular risk after an acute coronary event

Background and aimsThe pro-inflammatory alarmin S100A12 (EN-RAGE) and the soluble form of its receptor, the receptor for advanced glycation endproducts (sRAGE), have diverging roles in cardiovascular disease. In experimental studies, S100A12 promoted atherosclerosis while sRAGE treatment was anti-atherogenic and reduced myocardial infarction size by scavenging RAGE ligands. Here, we aimed to explore the links between S100A12, sRAGE, and long-term prognosis after an acute coronary syndrome (ACS). MethodsWe measured S100A12 and sRAGE in 524 patients within 24 h after an ACS, and again 6 weeks later in a subgroup of 114 patients. This subgroup also completed a follow-up echocardiography after 1 year. The median follow-up time for recurrent major adverse cardiovascular events (MACE), defined as recurrent ACS or cardiovascular death, was 25.7 ± 12.6 months. ResultsIn Cox proportional hazard analyses, baseline S100A12 and sRAGE were positively associated with the risk of MACE, independently of traditional cardiovascular risk factors. The association between sRAGE and MACE remained significant after additional adjustment for troponin T, NT-proBNP and hsCRP [HR 95%CI for highest versus lowest tertile 3.2 (1.5–6.5), p = 0.002]. High sRAGE was also associated with deteriorating left ventricular function and an increased rate of heart failure hospitalization post-discharge. In contrast, patients with increasing sRAGE at 6 weeks compared to baseline had lower incidence of recurrent ACS. ConclusionsOur data suggest that sRAGE has a dual, phase-dependent association with residual cardiovascular risk after ACS. These findings are important for the design and interpretation of future studies on sRAGE as biomarker and potential treatment in ACS patients.

Endothelial function as predictor in patients with coronary syndrome treated by percutaneous coronary intervention.

We aimed at identifying the predictive role of endothelial function assessed by the RH-PAT index (RHI) for future major cardiovascular events (MACEs) in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). We measured RHI in 308 subjects with ACS, and they were divided into the normal endothelial function (NEF) group and the endothelial dysfunction (DEF) group according to the RHI. The subjects were followed up for a mean of 16 months (interquartile range [IQR]: 14–20 months) after PCI treatment, and their MACEs were also recorded. Cumulative incidence curves were constructed for time-to-event variables with Kaplan–Meier estimates and compared using the log-rank test. The overall incidence of MACEs was 25.39% in the DEF group and 15.96% in the NEF group (P<0.05). Kaplan–Meier analysis also demonstrated a significantly higher probability of MACEs in the DEF group than in the NEF group (log-rank test: P<0.05). Multivariate Cox hazard analysis identified RHI (Model 2, adjusted by blood pressure, hazard ratio [HR]: 0.425; 95% confidence interval [CI]: 0.198–0.914; P=0.029) and SYNTAX score (HR: 1.043; 95% CI: 1.019–1.067; P<0.001) as independent predictors of future MACEs after PCI treatment in ACS patients. Endothelial function measured by reactive hyperemia-peripheral arterial tonometry (RH-PAT) is impaired in ACS subjects treated with PCI. The RHI was an independent predictor of MACEs, suggesting that RHI may be useful as a candidate biomarker in the risk stratification of patients with ACS after PCI treatment.

The short-term and long-term clinical efficacy of aspirin combined with ticagrelor in the treatment of acute coronary syndrome patients with non-revascularization

Objective To explore the short-term and long-term clinical efficacy of aspirin combined with ticagrelor in the treatment of acute coronary syndrome(ACS) patients with non-revascularization, to assess the improvement of cardiac function. Methods A total of 114 ACS patients with non-revascularization in Dajiang Hospital of Hangzhou were selected.They were randomly divided into control group and study group by random number table method, with 57 patients in each group.The control group was given aspirin and clopidogrel conventional therapy.The study group was treated with aspirin and ticagrelor.The clinical efficacy was evaluated.The Grace scores of ACS before and after treatment were evaluated, and the serum levels of lactate dehydrogenase (LDH) and creatine phosphokinase(CPK) were measured.The patients were followed up for 12 months, the incidence of primary and secondary end points and the occurrence of dyspnea were observed. Results The total effective rate of the study group was 87.72% (50/57), which was higher than 71.93%(41/57) of the control group, the difference was statistically significant(χ2=10.65, P<0.05). The incidence rates of primary end point and secondary end point of the study group were 12.28%(7/57) and 17.54%(10/57), respectively, which were lower than 21.05%(12/57) and 35.09% (20/57) of the control group, the differences were statistically significant(χ2=9.82, 10.13, all P<0.05). The incidence rate of dyspnea of the study group was 24.56%(14/157), which was higher than 3.51%(2/57) of the control group, the difference was statistically significant (χ2=10.96, P<0.05). The Grace score of the study group was (80.23±7.89)points, which was lower than (85.58±8.14) points of the control group, the difference was statistically significant(t=9.38, P<0.05). The levels of LDH and CPK of the study group were (217.06±44.34)U/L and (167.52±37.41)U/L, respectively, which were lower than (261.58±43.10)U/L and (225.48±38.26)U/L of the control group, the differences were statistically significant(t=10.06, 10.29, all P<0.05). Conclusion Aspirin combined with ticagrelor for ACS patients with non-revascularization can effectively inhibit platelet aggregation, the clinical efficacy is significant, the incidence of primary and secondary end points of patients with ACS was significantly reduced, the prognosis is good.While dyspnea rate increased, but does not affect the treatment of patients. Key words: Acute coronary syndrome; Aspirin; Ticagrelor

In-hospital acute coronary syndrome management in Europe: Pharmacological treatment trends, adequacy to the latest guidelines and its impact on vital status at discharge

Acute coronary syndrome (ACS) early management can be decisive and is subject to guidelines. To describe the variations of in-hospital pharmacological treatments of ACS patients in Europe over time, to describe the adequacy of the in-hospital pharmacological treatments of ACS patients with the latest ESC guidelines (2012 and 2015 ESC guidelines for STEACS and non-STEACS patients respectively), and to assess the link between treatment adequacy with guidelines and vital status at discharge. EUROTRACS (EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis) database was created by merging data from European studies and surveys, national/regional clinical registries of ASC patients. Beta-blockers, statins, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), and aspirin were considered. The analyses were performed separately for STEACS and non-STEACS patients. Due to missing data regarding the variables of interest (> 20%), only data from the Euro Heart Surveys I and II, the Greek, German and Spanish registries (respectively HELIOS, MONICA/KORA MI, MASCARA) have been used. Aspirin appeared to be steadily prescribed (91.2% in 2000 and 97.9% of ACS patients treated in 2010). Beta-blockers, statins and ACEI/ARB prescriptions have increased ( Fig. 1 ). Regarding adequacy to the guidelines, beta-blockers and statins seemed to be better prescribed over time whereas ACEI/ARB prescription adequacy decreased (but this comparison was partial since some patient's parameters, such as intolerance to statins or to ACEI, were not available). Same trends were observed in STEACS and non-STEACS patients. The final analyses are still in progress. Prescription of pharmacological treatment in ACS patients varied over time as well as the respect of the recommendations.

Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation.

Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1mg followed by 0.5mg 1h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are 'primed' to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β.

Das akute Koronarsyndrom

Acute coronary syndrome (ACS) is the working diagnosis of patients with acute chest pain and a presumed insufficient myocardial perfusion. Prognosis of myocardial infarction with delayed or incorrect treatment is poor, therefore rapid diagnosis is essential. Since chest pain is frequent, all medical personal is likely to be confronted with ACS patients in everyday practice. Even for cardiologist however, treatment of ACS patients can be challenging.

Abstract 13715: Colchicine Acutely Suppresses the NLRP3 Inflammasome in Acute Coronary Syndrome Patients Monocytes

Objectives: Inflammasome activation, with subsequent release of pro-inflammatory cytokines IL-1β and IL-18, has recently been implicated in atherosclerosis-associated inflammation. Here, in acute coronary syndrome (ACS) patients, we assessed (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. Methods: ACS patients (n=21) were randomized to oral colchicine (1.5mg) or no treatment, and compared with untreated healthy controls. Venous samples were drawn pre- (day 1) and 24h post- (day 2) treatment. Cultured monocytes were stimulated with ATP which facilitates the release of cleaved cytokines. Analysis of key inflammasome markers was performed in cell media and lysates. Results: Monocytes from untreated ACS patients secreted significantly higher levels of cleaved IL-1β and IL-18 vs healthy controls (p&lt;0.05 for both; Fig A). Colchicine treatment in ACS patients markedly reduced intracellular pro- and cleaved IL-1β protein levels as well as secreted cleaved IL-1β protein levels (Fig A) vs pre-treatment levels. Colchicine treatment significantly reduced pro-caspase-1 mRNA levels and secreted caspase1 protein levels (p&lt;0.05) vs untreated patients (Fig B). IL-18 levels were unaffected by treatment. In untreated ACS patients, inflammasome-related protein levels did not significantly change between day 1 and day 2 Conclusion: We show here, for the first time, that (1) monocytes from ACS patients are “primed” to secrete inflammasome-related cytokines and (2) short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing cellular protein secretion of IL-1β. These data, therefore, provide mechanistic insights into a potential role for colchicine in suppressing coronary inflammation in ACS patients.

Effect on short and long term clinical outcome of attenuated plaque in patients with acute coronary syndrome after percutaneous coronary intervention

Objective To explore the effect on prognosis of attenuated plaque (AP) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention(PCI). Methods This study was a prospective study which included 225 ACS patients who admitted to the cardiology and met the conditions between January 2009 and December 2011. Clinical data, intravascular ultrasound characteristics of plaque, blood flow in coronary angiography and cardiovascular complications within 30 days after PCI were recorded. The main form of follow-up was telephone follow-up, supplemented by patient follow-up and out-patient follow-up. Endpoint was major adverse cardiac events (MACE). Kaplan-Meier method was used to estimate survival rate. The survival difference between the two groups was compared using the Log-Rank test. Results Extravascular elastic membrane area (EEMA), plaque area (PA), plaque burden, remodeling index in AP group were significantly increased than those in non-AP group. Corrected TIMI frame count (CTFC) immediately after the balloon dilatation was significantly higher in AP group than in non-AP group. Recent overall complications were more frequently documented in AP group than in non-AP group, but long-term follow-up outcome of MACE-free survival curves showed no significant difference between the two groups. Conclusions Recent prognosis, not long-term prognosis, is affected by attenuated plaque in ACS patients after PCI, which help to stratify risk further and guide treatment in ACS patients. Key words: Echocardiography; Acute coronary syndrome; Attenuated plaque; Prognosis

Effects of Statin versus the Combination of Ezetimibe plus Statin on Serum Lipid Absorption Markers in Patients with Acute Coronary Syndrome.

Background. The use of statins is essential for aggressive lipid-lowering treatment in acute coronary syndrome (ACS) patients with dyslipidemia. Recently, elevation of sitosterol, a lipid absorption marker, was reported to be associated with premature atherosclerosis. The purpose of the present study was to examine the impact of ezetimibe, a selective intestinal cholesterol transporter inhibitor, in ACS patients. Methods. A total of 197 ACS patients were randomized to pitavastatin + ezetimibe (n = 100) or pitavastatin (n = 97). Low-density lipoprotein cholesterol (LDL-C) and sitosterol levels were evaluated on admission and after 12 weeks. Results. After 12 weeks, the pitavastatin + ezetimibe group showed a significantly greater decrease of sitosterol (baseline versus after 12 weeks; 2.9 ± 2.5 versus 1.7 ± 1.0 ng/mL, P < 0.001) than the pitavastatin group (2.7 ± 1.5 versus 3.0 ± 1.4 ng/mL). The baseline sitosterol level was significantly higher in patients with achieved LDL-C levels ≥ 70 mg/dL than in patients with levels < 70 mg/dL (3.2 ± 2.5 versus 2.4 ± 1.3 ng/mL, P = 0.006). Conclusions. Ezetimibe plus statin therapy in ACS patients with dyslipidemia decreased LDL-C and sitosterol levels more than statin therapy solo. Sitosterol Elevation was a predictor of poor response to aggressive lipid-lowering treatment in ACS patients.

ANMCO/SICI-GISE paper on antiplatelet therapy in acute coronary syndrome

Antiplatelet therapy is the cornerstone of the pharmacologic management of patients with acute coronary syndrome (ACS). Over the last years, several studies have evaluated old and new oral or intravenous antiplatelet agents in ACS patients. In particular, research was focused on assessing superiority of two novel platelet adenosine diphosphate (ADP) P2Y12 receptor antagonists (i.e. prasugrel and ticagrelor) over clopidogrel. Several large randomized controlled trials have been undertaken in this setting and a wide variety of pre-specified and post hoc analyses are available that evaluated the potential benefits of novel antiplatelet therapies in different subsets of patients with ACS. The aim of this document is to review recent data on the use of current antiplatelet agents for in-hospital treatment of ACS patients. For each drug or class of drugs, strong evidence and/or areas of uncertainty that warrant further research are highlighted by examining 10 subgroups of patients with ACS.

A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients

Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incremental-cost-effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.

Randomized Comparison of Ticagrelor versus Prasugrel in Patients with Acute Coronary Syndrome and Planned Invasive Strategy—Design and Rationale of the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 Trial

In acute coronary syndromes (ACS), a dual antiplatelet regimen with an adenosine diphosphate (ADP) receptor antagonist plus aspirin has become the cornerstone of treatment. The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater, more rapid and consistent platelet inhibition compared to their predecessor clopidogrel. Based on their advantages over clopidogrel in two landmark studies, both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation. Due to differences in ACS populations and conditions investigated, the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy cannot be reliably estimated from independent trials. To date, no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists. The aim of this multicenter, randomized, open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy.

In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: Prevalence, predictors and short-term outcome

P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P < .001, P = .03, P < .001 and P = .03 respectively). In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategy's choice, while switching to a novel agent may be associated with higher risk of bleeding.

Potent P2Y12 receptor inhibitors in patients with acute coronary syndrome

SummaryBlood platelets are highly activated in the setting of an acute coronary syndrome (ACS). This fact mandates the need for potent platelet inhibition in ACS patients and especially in patients undergoing a percutaneous coronary intervention (PCI). The 2nd generation thienopyridine clopidogrel has been the standard of treatment in the past. Due to its pharmacological properties including a delayed onset of action, a large response variability and an insufficient antiplatelet action in some patients (low responsiveness or high on-treatment platelet reactivity), there was a need to develop, to study and to introduce more potent agents with a fast, reliable and potent antiplatelet action. With the 3rd generation thienopyridine prasugrel and with ticagrelor two potent agents for antiplatelet treatment of ACS patients are available now. Both drugs have demonstrated their superiority compared to clopidogrel in terms of thrombotic risk reduction in large-scale randomized trials. However, for these agents and in line with the expectations towards a more potent anti platelet treatment regimen, a higher risk for bleeding was observed for prasugrel and ticagrelor. Further on, the new anti platelet agents have their own and characteristic contraindications and numerous issues to be considered in clinical practice.This review aims to provide an overview on the state of the art P2Y12 receptor directed inhibition in ACS patients with a focus on patients undergoing a coronary stenting procedure.