Setting Of Acute Coronary Syndrome Research Articles

Impact of tailored anti-P2Y12 therapies in acute coronary syndromes.

Acute coronary syndromes are a major disease burden and the prognosis has improved over the last decades due to improvement of medical and interventional treatments. Novel P2Y12-ADP-receptor antagonists have been introduced into clinical treatment offering more potent and rapid onset of action with the downside of increased bleeding risk. This special report will focus on interindividual variability of antiplatelet drugs in the setting of acute coronary syndromes and the current impact and potential future of point-of-care testing to personalize therapy aiming to improve prognosis in acute coronary syndrome patients.

Procalcitonin as an Early Predictor of Contrast-Induced Acute Kidney Injury in Patients With Acute Coronary Syndromes Who Underwent Percutaneous Coronary Intervention.

Contrast-induced acute kidney injury (CI-AKI) is a major issue after percutaneous coronary intervention (PCI), especially in the setting of acute coronary syndrome (ACS). Contrast-induced acute kidney injury is associated with increased mortality and morbidity. Inflammation plays an important role in the pathophysiology of CI-AKI. Procalcitonin (PCT) is introduced as a new marker of inflammation. We sought to examine whether admission PCT levels predict the development of CI-AKI. Patients (n = 814) were divided into 2 groups, namely, CI-AKI (-) and CI-AKI (+). An increase in serum creatinine of ≥0.5 mg/dL from baseline within 48 to 72 hours of contrast exposure was defined as CI-AKI. Contrast-induced acute kidney injury occurred in 96 (11.8%) patients. The PCT levels were significantly higher in patients with CI-AKI than in those without, 0.11 (0.056-0.495) vs 0.04 (0.02-0.078) µg/L; P < .001. After multivariable analysis, PCT remained a significant independent predictor of CI-AKI (odds ratio 2.544; 95% CI [1.207-5.347]; P = .014) as well as age, women, white blood cell, hemoglobin, glomerular filtration rate, creatine kinase myocarial band, and SYNTAX score. In conclusion, serum PCT levels are independently associated with a risk of CI-AKI in patients with ACS who underwent urgent PCI.

Overview of the 2014 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee Meeting Regarding Cangrelor

Landmark clinical trials have established the benefit of P2Y12 inhibitors in the setting of acute coronary syndrome and percutaneous coronary intervention. On February 12, 2014, the Medicines Company (Sponsor) presented efficacy and safety data regarding cangrelor to the Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee. The Sponsor sought approval for 2 indications: (1) in the setting of percutaneous coronary intervention for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with coronary artery disease and (2) in the setting of bridging therapy in patients with acute coronary syndrome or with stents who are at increased risk for thrombotic events (such as stent thrombosis) when oral P2Y12 therapy is interrupted because of surgery. The following is a summary of the data presented to the FDA by the Sponsor, the FDA's clinical review of cangrelor.

CRT-114 Echocardiographic Left Ventricular Hypertrophy Predicts In-hospital Heart Failure in Patients with Non-ST Elevation Myocardial Infarction

Left ventricular hypertrophy (LVH) is a well-known predictor of heart failure in the general population. However, its clinical significance in the setting of acute coronary syndrome has not been well established. We aimed to determine the predictive value of echocardiographic LVH for in-hospital

Ticagrelor: a novel drug for an old problem.

Cardiovascular disease and in particular, acute coronary syndromes are one of the principle causes of death in the industrialized countries. In the setting of acute coronary syndromes (both ST - segment or non ST - segment elevation myocardial infarction), platelets aggregation plays a key and central role in their development. Platelets are the mediators of hemostasis at sites of vascular injury, but they also mediate pathologic thrombosis; activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion promoting atherothrombotic disease. Recent patent relates to the methods and devices for treating atherosclerosis and to prevent in-stent restenosis or thrombosis. Because of the importance of platelets involvement in the initiation and propagation of thrombosis, antiplatelet drugs have a source of research; in the recent past, new antiplatelet drugs (such as ticagrelor) have been studied and placed in the routine therapy. The aim of this paper is to summarize the pharmacological properties and the clinical characteristics of ticagrelor.

Predictors of Long Term Outcomes in 11,441 Consecutive Patients Following Percutaneous Coronary Interventions

Given the vicissitudes of percutaneous coronary intervention (PCI) technology, epidemiology, and mode of practice, the aim of this study was to define contemporary outcome predictors in a very large consecutive patient cohort. Data from 11,441 consecutive patients who underwent PCI at a tertiary medical center from April 2004 to September 2013 are presented. A comprehensive database was built using various data sources, with outcome end points defined as all-cause mortality and as a composite of death or nonfatal myocardial infarction during follow-up. Candidate variables to influence outcome were chosen a priori and were tested using multivariate time-dependent models to estimate each interaction. Mean follow-up was 5.5 years (range 3 months to 9.5 years). The cohort consisted of 75% men, 42% patients with diabetes, and 61% patients who underwent PCI in acute coronary syndrome settings and 7.8% for ST-elevation myocardial infarction. Drug-eluting stents were used in 43.4% of patients, bare-metal stents in 52%, and balloon angioplasty alone in 4.6%. In multivariate analysis, in addition to already well-recognized predictors of death or myocardial infarction such as advanced age (hazard ratio [HR] 1.031, p <0.001), female gender (HR 1.23, p <0.001), urgent setting (HR 1.23, p <0.001) and diabetes mellitus (HR 1.28, p <0.001), we particularly noted previous anemia (HR 1.55 p <0.001), previous chronic kidney injury (HR 1.93, p <0.001) and previous moderate to severe left ventricular dysfunction (HR 2.29, p <0.001). Drug-eluting stent placement was associated with better outcomes (HR 0.70, p <0.001). In conclusion, this analysis confirms the effect of some known predictors of PCI outcomes. However, the extent of their effect is modest, while other predictors may have a greater influence on outcomes. Risk stratification of PCI patients should take into account kidney injury, anemia, and left ventricular function. Drug-eluting stents provide sustained benefit.

Impact of Human Development Index on the profile and outcomes of patients with acute coronary syndrome

ObjectiveTo study the impact of national economic and human development status on patient profiles and outcomes in the setting of acute coronary syndrome (ACS).MethodsWe conducted a retrospective analysis of the...

Outcomes in patients with cardiogenic shock following percutaneous coronary intervention in the contemporary era: an analysis from the BCIS database (British Cardiovascular Intervention Society).

This study sought to determine mortality rates among cardiogenic shock (CGS) patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome in the contemporary treatment era and to determine predictors of mortality. It is unclear whether recent advances in pharmacological and interventional strategies have resulted in further improvements in short- and long-term mortality and which factors are associated with adverse outcomes in patients presenting with CGS and undergoing PCI in the setting of acute coronary syndrome. This study analyzed prospectively collected data for patients undergoing PCI in the setting of CGS as recorded in the BCIS (British Cardiovascular Intervention Society) PCI database. In England and Wales, 6,489 patients underwent PCI for acute coronary syndrome in the setting of CGS. The mortality rates at 30 days, 90 days, and 1 year were 37.3%, 40.0%, and 44.3%, respectively. On multiple logistic regression analysis, age (for each 10-year increment of age: odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.51 to 1.68; p < 0.0001), diabetes mellitus (OR: 1.47, 95% CI: 1.28 to 1.70; p < 0.0001), history of renal disease (OR: 2.03, 95% CI: 1.63 to 2.53; p < 0.0001), need for artificial mechanical ventilation (OR: 2.56, 95% CI: 2.23 to 2.94; p < 0.0001), intra-aortic balloon pump use (OR: 1.57, 95% CI: 1.40 to 1.76; p < 0.0001), and need for left main stem PCI (OR: 1.90, 95% CI: 1.62 to 2.23; p < 0.0001) were associated with higher mortality at 1 year. In this large U.K. cohort of patients undergoing PCI in the context of CGS, mortality remains high in spite of the use of contemporary PCI strategies. The highest mortality occurs early, and this time period may be a particular target of therapeutic intervention.

Abstract 19569: High-sensitive Troponin T Cut-off Value for Myocardial Infarction After Vascular Surgery

Introduction: Isolated high sensitive cardiac troponin T (hsTnT) elevations after vascular surgery are frequent and may lead to over diagnosis of myocardial infarction (MI). The aim of our study was to determine the accuracy of the current hsTnT cut-off value in the setting of acute coronary syndrome (ACS) after vascular surgery. Methods: Between August 2012 and March 2014, we included 337 consecutive patients submitted to arterial vascular surgery for which cardiac perioperative evaluation was requested. Perioperative surveillance included 12-lead electrocardiogram and hsTnT measurements on the three days following surgery. Patients were followed-up by cardiologists until hospital discharge and monitored for ACS. A receiver operating characteristics (ROC) curve analysis was performed to determine the hsTnT cut-off value with better accuracy for the diagnosis of perioperative ACS. Results: Of the 337 patients included, 240 (71.2%) presented hsTnT elevation above the manufacturer-provided cut-off value (0.014 ng/ml), whereas 22 (6.5%) fulfilled criteria for ACS. Median post-operative peak hsTnT of ACS patients were 0.215 ng/ml (IQR 0.043-0.493 ng/ml), versus 0.02 ng/ml (IQR 0.012-0.038 ng/ml) in patients that did not have events (P&lt;0.001). After performing a ROC curve analysis (AUC = 0.876), we found that the manufacture-provided cutoff hsTnT value yielded a sensitivity of 100% and specificity of only 35% for diagnosis of perioperative ACS. A new hsTnT cutoff value of 0.0415 ng/ml was obtained with 86.4% sensitivity and 77% specificity for the diagnosis of perioperative ACS. Ninety-two patients (27.3%) had hsTnT elevations above the proposed new cutoff. Conclusion: A different hsTnT cutoff value of 0.0415 ng/ml is proposed and could be more useful for the diagnosis of perioperative ACS.

Glucose-insulin-potassium therapy in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials.

BackgroundGlucose-insulin-potassium (GIK) has been advocated in the setting of acute coronary syndrome (ACS) to reduce ischemia-related arrhythmias and myocardial injury. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess whether the use of GIK infusions >3 or <3 hours after the onset of symptoms reduce mortality or cardiac arrest.MethodsElectronic databases (Medline, EMBASE, and Cochrane Central Register of Controlled Trials) and references of retrieved articles were searched for RCTs evaluating the effect of GIK infusions, <3 hours or >3 hours after the onset of symptoms, on mortality and/or cardiac arrest. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each outcome.ResultsNine trials were identified and eligible for review. The summary OR for in-hospital mortality was 1.01 (95% CI 0.94 to 1.09), based on 2,542 deaths among 27,294 patients. The subgroup analysis according to the study enrollment time (within 3 hours [OR, 0.77, 95% CI 0.50-1.16], vs. >3 hours [OR, 0.90; 95% CI, 0.67-1.21]) did not reveal any difference in mortality.ConclusionsAdministration of GIK in ACS patients does not significantly reduce mortality whether or not GIK administration >3 or <3 hours after the onset of symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-169) contains supplementary material, which is available to authorized users.

The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome.

In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet–monocyte and platelet–neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events. Electronic supplementary materialThe online version of this article (doi:10.1007/s11239-014-1142-x) contains supplementary material, which is available to authorized users.

Troponins in heart failure

The signs and symptoms of heart failure are frequently unspecific and correlate poorly with objective indices of cardiac function. Objective assessment of cardiac function by echocardiography or other imaging modalities also correlate poorly with symptomatic status and functional capacity. Accordingly, there is a need for circulating biomarkers that can provide incremental diagnostic and prognostic information to the existing armamentarium of tests. The introduction of more sensitive assays that allow determination of very low circulating concentrations of the myofibrillar proteins cardiac troponin I and T has not only resulted in improved diagnostic accuracy in the setting of acute coronary syndromes. The high sensitivity assays have also shown that cardiac troponins are frequently found chronically circulating in a variety of acute and chronic, cardiac and non-cardiac disease conditions, including acute heart failure and chronic symptomatic and asymptomatic left ventricular dysfunction. Cardiac troponin I and T provide may provide clinically useful prognostic information both concerning the future risk of developing heart failure in asymptomatic subjects and the risk of fatal events and hospital admissions in those with already established heart failureThis review summarizes current literature on the clinical performance and utility of cardiac troponin measurements as diagnostic and prognostic tools in patients with symptomatic heart failure, as well as in those with asymptomatic left ventricular dysfunction, and clinical phenotypes at high risk for developing heart failure, including stable coronary artery disease, left ventricular hypertrophy, and aortic stenosis.

Genetic variation at glucose and insulin trait loci and response to glucose-insulin-potassium (GIK) therapy: the IMMEDIATE trial.

The mechanistic effects of intravenous glucose, insulin and potassium (GIK) in cardiac ischemia are not well understood. We conducted a genetic sub-study of the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial to explore effects of common and rare glucose and insulin-related genetic loci on initial to 6-h and 6- to 12-h change in plasma glucose and potassium. We identified 27 NOTCH2/ADAM30 and 8 C2CD4B variants conferring a 40-57% increase in glucose during the first 6 h of infusion (P<5.96 × 10(-6)). Significant associations were also found for ABCB11 and SLC30A8 single-nucleotide polymorphisms (SNPs) and glucose responses, and an SEC61A2 SNP with a potassium response to GIK. These studies identify genetic factors that may impact the metabolic response to GIK, which could influence treatment benefits in the setting of acute coronary syndromes (ACS).

Long‐term safety and efficacy of second‐generation everolimus‐eluting stents compared to other limus‐eluting stents and bare metal stents in patients with acute coronary syndrome

This study aimed to investigate the long-term safety and efficacy of everolimus-eluting stents (EES) compared with other limus-eluting stents and bare metal stents (BMS) in ACS patients. There have been concerns about the long-term safety of drug-eluting stents in the setting of acute coronary syndrome. The study cohort included 1,612 patients presenting with acute coronary syndrome who underwent BMS, SES, E-ZES, or EES implantation. End points included probable or definite stent thrombosis and major adverse cardiovascular events (MACE), defined as a composite of all-cause death, Q-wave myocardial infarction, and target lesion revascularization up to 3 years. The overall MACE rates were significantly higher for both BMS and SES, but not E-ZES, when compared with EES (EES vs. BMS: HR 2.68, 95% CI 1.91-3.78, P <0.001; EES vs. SES: HR 1.75, 95% CI 1.24-2.47, P = 0.001 and EES vs. HR 1.08, 95% CI 0.65-1.77, P = 0.72). Stent thrombosis rates were similar for EES, E-ZES, and BMS but higher for SES throughout the 3-year follow-up (EES vs. BMS: HR 1.02, 95% CI: 0.31-3.35, P = 0.973; EES vs. SES: HR 4.90, 95% CI: 1.75-13.69, P = 0.002 and EES vs. HR 1.63, 95% CI 0.37-7.31, P = 0.449). There was an improvement in the long-term outcome for MACE with EES when compared to earlier-generation stents, but this was comparable with the 2nd-generation E-ZES. There was no additional risk of early or late stent thrombosis in EES when compared with BMS.

Use of bioresorbable vascular scaffolds in patients with stable angina and acute coronary syndromes. Polish National Registry.

Current revascularisation guidelines recommend coronary stenting with either a bare metal stent or a drug eluting stent. The results of bioresorbable vascular scaffold (BVS) implantation in the setting of both stable angina and acute coronary syndrome (ACS) have proven to be both safe and efficacious. To describe current use and real life experience among Polish percutaneous coronary intervention (PCI) operators in using BVS since they were made commercially available on our market. We performed a one-arm retrospective observational registry study which enrolled patients in 30 invasive cardiology centres in Poland who had their PCI procedure performed between October 2012 and November 2013. All patients who received at least one BVS stent during index PCI were included in the registry. There were no additional inclusion or exclusion criteria. There were 591 patients enrolled in the registry in 30 centres in Poland. Of these, 48% were with stable angina (CCS I-III) and 52% with ACS (23% unstable angina, 18% NSTEMI and 11% STEMI). Radial access for PCI was used in 70% of cases. Left anterior descending was the target lesion in 48% of patients and predilatation used in 90%. PCI complications occurred very rarely with dissection in 2.9% of patients, slow-flow in 0.5%, no-reflow in 0.17%, and side branch occlusion in 0.33%. Technical success, defined as successful BVS delivery to the lesion, was achieved in all cases (100%). There were no periprocedural deaths. The early in-hospital results of this large scale national registry of 'real world' utilisation of BVS in Poland present excellent device performance in a properly selected group of patients with appropriate lesion preparation.

Safety and efficacy of first-generation and second-generation drug-eluting stents in the setting of acute coronary syndromes.

Drug-eluting stents (DESs) are known to reduce in-stent restenosis rate, compared with bare metal stents (BMSs). Stent thrombosis, one of the most dangerous complications of DES, has emerged as a major concern. This issue has limited the use of DES in unstable coronary artery disease till recent years. In fact, acute coronary syndrome (ACS) and the subsequent activation of the hemocoagulative pathway could represent a prothrombotic environment, thus limiting the use of DES in this situation. Nowadays, there is increasing evidence in literature of similar stent thrombosis rates both for BMS and DES in ACS, and most interventional cardiologists are confident with the use of DES in ACS. The aim of this article is to review the current literature on this topic in order to compare first-generation and second-generation DES vs. BMS as concerns safety and efficacy.

Lipoproteins as biomarkers and therapeutic targets in the setting of acute coronary syndrome.

The period following an acute coronary syndrome (ACS) represents a critical time frame with a high risk for recurrent events and death. The pathogenesis of this increase in clinical cardiovascular disease events after ACS is complex, with molecular mechanisms including increased thrombosis and inflammation. Dyslipoproteinemia is common in patients with ACS and predictive of recurrent cardiovascular disease events after presentation with an ACS event. Although randomized clinical trials have provided fairly convincing evidence that high-dose statins reduce the risk of recurrent cardiovascular events after ACS, there remain questions about how aggressively to reduce low-density lipoprotein cholesterol levels in ACS. Furthermore, no other lipid-related interventions have yet been proven to be effective in reducing major cardiovascular events after ACS. Here, we review the relationship of lipoproteins as biomarkers to cardiovascular risk after ACS, the evidence for lipid-targeted interventions, and the potential for novel therapeutic approaches in this arena.

71 Percutaneous Coronary Intervention (PCI) Risk Scores Predicting Inpatient Mortality and Major Adverse Cardiac Events (MACE) are Poorly Concordant in High Risk Patients

BackgroundHigh-risk percutaneous coronary intervention (PCI) procedures are being performed in greater numbers, in older patients with multiple comorbidities, and increasingly in the setting of acute coronary syndromes. Estimating inpatient PCI...

Clinical characteristics and outcomes of acute coronary syndrome patients with left anterior hemiblock

ObjectiveWe aimed to study the relationships between left anterior hemiblock (LAHB) and the patient characteristics, management, and clinical outcomes in the setting of acute coronary syndromes (ACS).MethodsAdmission ECGs of patients...

Second-generation versus first-generation drug-eluting stents for the treatment of patients with acute coronary syndromes and obstructive coronary artery disease

Randomized trials and registries have shown that drug-eluting stents (DES) have an overall better performance than bare-metal stents in patients treated in the setting of both ST-segment and non-ST-segment elevation acute coronary syndromes, mainly by reducing restenosis. Whether or not the use of newer second-generation devices (vs. first-generation DES) differs in these high-risk patients remains to be determined. In a single-centre prospective registry, 3266 patients underwent a percutaneous coronary intervention with at least one DES from January 2003 to December 2009. Of these, 1423 (43.6%) were treated in the setting of an acute coronary syndrome, using either first-generation-only DES [paclitaxel or sirolimus; n=923 (64.9%)] or second-generation-only [zotarolimus or everolimus; n=500 (35.1%)]. The occurrence of death from any cause, nonfatal myocardial infarction or target vessel failure (composite primary endpoint) was compared between these two groups; repeat revascularization of the index stented lesion and definite stent thrombosis [according to the academic research consortium (ARC) definition] were assessed as isolated secondary outcomes. At a median follow-up of 598 days (interquartile range 453-1206), the incidence of death was 10.7% (152), 136 patients (9.6%) had a new myocardial infarction and target vessel failure events occurred in 147 patients (10.3%). Disparity in the follow-up duration was accounted for by considering only the 1-year major adverse cardiac event rate (n=161; 11.3%). After adjustment for baseline characteristics using a Cox proportional hazard model, we could not find a significant difference in the incidence of the composite primary endpoint at 1-year between first-generation (10.8%) and second-generation DES (12.2%) [hazard ratio (HR): 1.1; 95% confidence interval (CI): 0.82-1.57, P=0.463], nor in the occurrence of repeat target lesion revascularization (3.6 vs. 4.4%; HR 1.35; 95% CI 0.77-2.34; P=0.293). In a per patient analysis, at 1 year, ARC-definite ST was documented in 1.0% of patients treated with second-generation DES versus 2.8% in those treated with first-generation DES (corrected HR 0.36; 95% CI 0.14-0.94; P=0.037), owing mostly to a higher difference in late ST. Our results suggest that both first-generation and second-generation DES seem to be similarly effective in patients undergoing a percutaneous coronary intervention in the setting of acute coronary syndromes. However, newer second-generation devices may offer potential advantages because of a significantly lower incidence of ARC-definite ST.