ST-elevation Acute Coronary Syndrome Patients Research Articles

Unfolding the reality of the smoking paradox in a South Asian cohort of patients presenting with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention.

Smoking is a potent risk factor for coronary artery disease, but there is controversy about its protective nature in terms of prognosis in ST-elevation acute coronary syndrome patients undergoing primary percutaneous coronary intervention. So, the main objective of this study is to unfold this controversy in a South Asian population in terms of clinical angiographic parameters and its in-hospital outcomes. In this study, we included 1756 consecutive patients diagnosed with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention. Patients were classified into smokers and non-smokers, and the in-hospital mortality rate was compared. Multivariable logistic regression analysis was performed to evaluate the paradoxical role of smoking. Smokers were younger (53.78 ± 11.16 years vs 56.43 ± 11.17 years; p < 0.001) and more frequently men (98.7% vs 69.9%; p < 0.001) and had less diabetes (19.6% vs 44.8%; p < 0.001) and hypertension (38.5% vs 64.9%; p < 0.001). Smokers presented less frequently in Killip III (5.6% vs 8.1%; p < 0.001) and Killip IV (2.5% vs 4.8%; p < 0.001). Smokers mostly had single vessel disease (41.7% vs 34.4%; p = 0.013), whereas non-smokers had the multi-vessel disease and frequently presented with total occlusion of the culprit vessel (64.6% vs 58.8%; p = 0.040). Smokers have significantly lesser mortality (1.8% vs 4.3%; p = 0.009) compared to non-smokers with an odds ratio of 0.41 (95% confidence interval (CI): 0.21-0.82, p = 0.011); however, adjusted odds ratio on multivariable analysis was 0.67 (95% CI: 0.31-1.41, p = 0.290). The paradoxical protective role of smoking is the confounding effect of mainly younger age, less coronary artery disease burden, lower prevalence of diabetes and hypertension, and lower Killip III/IV at presentation.

Efficacy of clopidogrel and ticagrelor under NT-proBNP in hospitalized ST-elevation acute coronary syndrome patients on percutaneous coronary intervention: CCC-ACS Project Analysis

BackgroundRisk stratification with specific biomarkers is proposed for tailored P2Y12 inhibitor therapy in patients with STEMI. MethodsThis nationwide registry and quality improvement study is from November 1, 2014, to June 30, 2017. In total, 11,512 STEMI patients received aspirin and P2Y12 receptor inhibitor (clopidogrel or ticagrelor) and underwent PCIs in hospitals. Of the patients, 2992 were prescribed ticagrelor and 8520 clopidogrel. The primary effectiveness outcome was major adverse cardiovascular and cerebrovascular events (MACCE: cardiac death, myocardial infarction, stent thrombosis, in-hospital ischemic stroke). The primary safety outcome was in-hospital major bleeding. ResultsMACCE incidence was lower in the ticagrelor group than in the clopidogrel group (0.8% versus 1.2%; P=0.046), but under different NT-proBNP levels, cumulative hazards of MACCE were without statistical significance. Bleeding rates were higher in the ticagrelor group than in the clopidogrel group (all bleeding: 9.9% versus 6.9%, P<0.001; major bleeding: 4.0% versus 2.7%, P<0.001). The higher cumulative hazard of bleeding could be identified in the Kaplan–Meier curves. In the multivariate analysis, ticagrelor increased bleeding events, compared with clopidogrel, at NT-proBNP >1800 ng/L patients (all bleeding: HR 1.46; 95%CI, 1.07–2.01; major bleeding: HR 1.68, 95%CI, 1.03–2.74), but a low effect was found in those with lower NT-proBNP level. Subgroup analyses show that ticagrelor increased major bleeding in patients with left ventricular ejection fraction (LVEF) <0.50 (HR 3.29; 95% CI 1.61–6.74) (interaction p=0.03). ConclusionWe found that ticagrelor, compared with clopidogrel, increased bleeding complications in hospitalized patients with NT-proBNP>1800 ng/L, especially in patients with EF < 0.50.

Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during percutaneous coronary intervention for acute coronary syndrome

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non–ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.

Long-term survival and causes of death in patients with ST-elevation acute coronary syndrome without obstructive coronary artery disease.

We aimed to study survival and causes of death in patients with ST-elevation acute coronary syndrome (STE-ACS) with and without obstructive coronary artery disease (CAD). We included 4793 consecutive patients with STE-ACS triaged for acute coronary angiography at a large cardiac invasive centre (2009-2014). Of these, 88% had obstructive CAD (stenosis ≥50%), 6% had non-obstructive CAD (stenosis 1-49%), and 5% had normal coronary arteries. Patients without obstructive CAD were younger and more often female with fewer cardiovascular risk factors. Median follow-up time was 2.6 years. Compared with patients with obstructive CAD, the short-term hazard of death (≤30 days) was lower in both patients with non-obstructive CAD [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.27-0.89, P = 0.018] and normal coronary arteries (HR 0.31, 95% CI 0.11-0.83, P = 0.021). In contrast, the long-term hazard of death (>30 days) was similar in patients with non-obstructive CAD (HR 1.15, 95% CI 0.77-1.72, P = 0.487) and higher in patients with normal coronary arteries (HR 2.44, 95% CI 1.58-3.76, P < 0.001), regardless of troponin levels. Causes of death were cardiovascular in 70% of patients with obstructive CAD, 38% with non-obstructive CAD, and 32% with normal coronary arteries. Finally, patients without obstructive CAD had lower survival compared with an age and sex matched general population. STE-ACS patients without obstructive CAD had a long-term risk of death similar to or higher than patients with obstructive CAD. Causes of death were less often cardiovascular. This suggests that STE-ACS patients without obstructive CAD warrant medical attention and close follow-up.

ANTIPLATELET TREATMENT IN ST ELEVATION ACUTE CORONARY SYNDROME UNDER REAL CLINICAL CIRCUMSTANCES: THE DYNAMICS OF THROMBOCYTE FUNCTION

Aim. To evaluate the dynamics of thrombocyte functional activity (TFA) under antiplatelet treatment conditions which include the branded, and generic compounds as well, in ST elevation acute coronary syndrome patients (STEACS) in routine clinical practice. Material and methods. The open-label prospective study was done, including STEACS patients stratified according to the kind of antiplatelet in-patient treatment (original and/or generics). As an endpoint, we used the surrogate — functional activity of thrombocytes (TFA), measured by impedance and luminescent aggregatometry at 1 and 7 day from STEACS onset. Results. By the inclusion, baseline point all patients were comparable by TFA. On double antiplatelet therapy (DAT) by the 7th day of STEACS there was statistically significant difference of all ADP-induced thrombocyte aggregation. There was difference in ADP-induced platelet aggregation depending on the DAT variant, which included the original drug and generic. Conclusion. In STEACS patients the level of aggregation activity of platelets does significantly differ from the kind of antiplatelet treatment. Usage of the branded and generic compounds of the came antiplatelet agent by the same regimen does differ by different grade and dynamics of platelets activeness suppression.

ROLE OF THE VARIABLE SITES G-1082A AND C-592A OF GENE IL10 IN DEVELOPMENT OF ONE YEAR ADVERSE OUTCOMES OF ST ELEVATION ACUTE CORONARY SYNDROME

Aim. Evaluation of the association of variation sites G-1082A (rs3024491) and C-592A (rs1800872) gene IL10 with one year outcomes of ST elevation acute coronary syndrome (STEACS). Material and methods. Totally, 178 patients included, with STEACS in whom the polymorphisms C-592А (rs1800872) and G-1082А (rs3024491) of the gene IL10 were checked. Genotyping was done with TaqMan “iCycler iQ” (BIO-RAD, USA). To the control group 185 relatively healthy persons included living in Kemerovo city. In 93, the concentration of interleukin-10 (IL-10) was measured by the hard-phase immune-enzyme assay, by BIOSOURCE (Belgium). Reference values of IL-10 were set at 2,98 (1,75-4,31) pg/mL. At the one-year stage, endpoints developed in 42 (23,5%) patients, progressive angina — in 30 (16,8%); cardiovascular mortality for one year reached 1,1% (n=2), nonfatal myocardial infarction developed in 6 (3,4%), ischemic stroke — in 4 (3,2%) patients. Results. While comparing IL-10 concentrations in STEACS with the reference values in Kemerovo city inhabitants, relatively low concentration was revealed in STEACS patients (0,38 vs 2,98 pg/mL; p=0,001). Association analysis of the variation sites of IL-10 with adverse outcomes during one year showed that genotype А/С rs3024491 (G-1082А) of gene IL10 is associated with the development of adverse outcome after NSTEACS. Endowment analysis towards the endpoint during 12 months showed that the most adverse is heterozygous carriage of А/С rs3024491 (G-1082А) gene IL10 (р=0,048). Conclusion. In NSTEACS patients genotype С/С rs1800872 (С-592А) gene IL10 associated with lots of cardiovascular risk factors, but genotype А/А rs3024491 (G-1082А) on the contrary, shows associations with protective factors. Genotype A/C of polymorphic variant rs3024491(G-1082А) gene IL10 is associated with adverse yearly outcomes in STEACS patients.

Biomarkers in Relation to the Effects of Ticagrelor in Comparison With Clopidogrel in Non–ST-Elevation Acute Coronary Syndrome Patients Managed With or Without In-Hospital Revascularization

Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial. Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, and stroke in medically managed patients (P<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT ≥14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive group Hs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT. URL:http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Troponin-Specific Autoantibody Interference in Different Cardiac Troponin I Assay Configurations

Autoantibodies to cardiac troponins (cTnAAb) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays. The aim of this study was to explore the degree of cTnAAb interference in different cTnI assay configurations. Ternary troponin complex was added into samples (serum or plasma, n = 132, 68% cTnAAb positive) from individuals without known cardiac conditions. The recovery of cTnI was then measured with 6 investigational cTnI assays (2, 3, or 4 antibodies per assay). Three of these assays were then selected for further comparison by use of samples (plasma, n = 210, 33% cTnAAb positive) from non-ST-elevation acute coronary syndrome patients in the FRISC-II (FRagmin/Fast Revascularisation during InStability in Coronary artery disease) cohort. Finally, these results were compared to those obtained with 3 commercial cTnI assays. Analytical recoveries varied widely among the 6 investigational assays. Notably the low recoveries (median 9%) of the midfragment-targeting reference assay were normalized (median 103%) with the use of the 4-antibody assay construct (3 capture, 1 tracer antibody) with only 1 antibody against a midfragment epitope. Reduced analytical recoveries correlated closely with measured autoantibody amounts. cTnI concentrations from cTnAAb-positive patient samples determined with 3 investigational assays confirmed the reduced concentrations expected from the low analytical recoveries. The results from the commercial cTnI assays with antibody selections representative for contemporary assay constructs revealed a similar underestimation (up to 20-fold) of cTnI in cTnAAb-positive samples. A novel cTnI assay deviating from the conventional IFCC-recommended midfragment approach substantially improves cTnI detection in samples containing cTnAAbs.

Underutilization of clopidogrel and glycoprotein IIb/IIIa inhibitors in non–ST-elevation acute coronary syndrome patients: The Canadian Global Registry of Acute Coronary Events (GRACE) experience

There are limited contemporary data on the early use of clopidogrel or glycoprotein (Gp) IIb/IIIa inhibitors, alone versus combination therapies, in non-ST-elevation acute coronary syndrome (NSTE-ACS). This study included 5,806 Canadian NSTE-ACS patients with elevated cardiac biomarker and/or ST deviation on presentation in the prospective GRACE between 2003-2007. We stratified the study population according to the management strategy (non-invasive vs invasive) and into low-(GRACE risk score <or=108), intermediate- (109-140), and high-risk groups (>or=141). Overall, 3,893 patients (67.1%) received early (<or=24 hours of admission) antiplatelet therapy; the rates of use were 76%, 73%, and 57% in the low-, intermediate-, and high-risk groups, respectively (P for trend < .001). Only 54% of the conservatively managed patients and 12% of the invasively managed patients received early clopidogrel and GpIIb/IIIa inhibitors, respectively. High-risk patients were less likely (adjusted odds ratio = 0.48, 95% CI 0.39-0.59, P < .001) to receive early clopidogrel or GpIIb/IIIa inhibitors, whereas in-hospital catheterization was an independent positive predictor (adjusted odds ratio = 2.02, 95% CI 1.74-2.34, P < .001) of use. In this contemporary NSTE-ACS population, both clopidogrel and GpIIb/IIIa inhibitors were targeted toward patients treated with an invasive strategy but paradoxically toward the lower-risk group. In particular, clopidogrel appeared to be underused among conservatively managed patients despite its proven efficacy, whereas GpIIb/IIIa inhibitors were administered to only a minority of the high-risk patients with elevated cardiac biomarkers. Our findings emphasize the ongoing need to promote the optimal use of evidence-based antiplatelet therapies among high-risk patients with NSTE-ACS.

Autoantibodies to Cardiac Troponin Associate with Higher Initial Concentrations and Longer Release of Troponin I in Acute Coronary Syndrome Patients

Cardiac troponin (cTn) is an established marker of myocardial infarction. Pronounced heterogeneity and the minute amounts released into the circulation constitute significant challenges for cTn detection. Recently, autoantibody formation to cTn was shown to be common and to interfere with immunoassay performance. In this study, we investigated cTn autoantibodies and cardiac troponin I (cTnI) in acute coronary syndrome (ACS) patients over a 1-year period after the index event. We used a second-generation cTnI assay designed to reduce the interference of cTn autoantibodies. The assay for cTn autoantibodies used 2 anti-cTnI antibodies to capture the ternary cTnI-complex, enabling unrestricted binding of the autoantibodies, which were detected with a labeled antihuman IgG antibody. We analyzed serum samples from 81 non-ST-elevation ACS patients taken at admission and after 1 week and 3 and 12 months. We found 14 cTn autoantibody-positive patients (21%) among the 67 cTnI-positive and none among the 14 cTnI-negative patients. Nine were autoantibody-positive at admission, and 5 became positive at 1 week. Autoantibody signals significantly increased in the 1-week and 3-month samples. At all time points, cTnI was significantly increased in the autoantibody-positive group relative to the negative group. Persistent cTnI elevations at 3 and 12 months were seen in the patients already autoantibody positive at admission. During ACS, patients with cTn autoantibodies have higher cTnI release and therefore larger myocardial damage than patients without autoantibodies. Their cTnI release also lasts longer, at least months. The possible prognostic impact of these observations must be evaluated in larger clinical cohorts.

Stopping the Hemorrhage

Aggressive management of high-risk non–ST-elevation acute coronary syndrome patients has focused on reducing ischemic complications with potent medications and mechanical interventions1,2 but at the cost of increased rates of major bleeding and associated adverse outcomes.3,4 The American College of Cardiology/American Heart Association 2007 guidelines for management of patients with unstable angina/non–ST-elevation myocardial infarction (NSTEMI)1 stress the importance of balancing antithrombotic and interventional therapies with therapeutic risk, and they urge special attention in groups at high bleeding risk, including women, the elderly, and those with renal insufficiency. For risk-prone groups, careful selection and dose adjustment of antithrombotics is encouraged, but no specific instruction for calculating bleeding risk or modifying treatment is provided. Article p 1873 The European Society of Cardiology’s 2007 guidelines for the diagnosis and treatment of non–ST-segment elevation acute coronary syndromes2 also recognize and devote a special section to bleeding complications, covering predictors of bleeding risk, the impact of bleeding on prognosis, the management of bleeding complications, and the impact of blood transfusions on outcomes. Major bleeding has been reported in 2% to 8% of non–ST-elevation acute coronary syndrome patients, with higher rates noted in broad-based registries (as in CRUSADE: Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines) than in controlled clinical trials. Complicating therapeutic decision making is the observation that baseline predictors of bleeding, ie, old age, female sex, renal dysfunction, and baseline anemia, also predict the risk of death due to ischemic complications. The impact of bleeding on prognosis is increasingly recognized. Major bleeding in the Global Registry of Acute Coronary Events (GRACE) was significantly associated with in-hospital death (adjusted OR 1.645). In registries and trials of more than 30 000 patients, major bleeding was associated with a 4-fold increase in the …

Impact of In-Hospital Revascularization on Survival in Patients With Non–ST-Elevation Acute Coronary Syndrome and Congestive Heart Failure

Patients with non-ST-elevation acute coronary syndrome complicated by congestive heart failure (CHF) have a poor prognosis. The aims of this study were to describe the use of revascularization in non-ST-elevation acute coronary syndrome and CHF and to analyze its impact on survival. In the Global Registry of Acute Coronary Events, 29 844 patients with non-ST-elevation acute coronary syndrome were enrolled at 120 hospitals in 14 countries between April 1999 and June 2007; 4953 had CHF at presentation. One fifth of the patients with CHF underwent revascularization versus 35% of those without CHF (P<0.001). Among CHF patients, revascularized patients had lower-risk baseline clinical characteristics than nonrevascularized patients and were more likely to receive evidence-based cardiac medications. Hospital rates were not affected by revascularization (adjusted hazard ratio 0.97, 95% confidence interval 0.72 to 1.33, P=0.87). Death from discharge to 6-month follow-up was lower in patients who underwent revascularization than in those who did not (odds ratio 0.51, 95% confidence interval 0.35 to 0.74, P<0.001). This difference persisted after adjustment for GRACE risk score variables, country, and propensity for revascularization (odds ratio 0.58, 95% confidence interval 0.40 to 0.85, P=0.005). When revascularization as a time-varying covariate was taken into account in an adjusted Cox regression, the rate of death was again lower in patients undergoing revascularization (hazard ratio 0.64, 95% confidence interval 0.45 to 0.93, P=0.02). This observational study suggests a low use of in-hospital revascularization in non-ST-elevation acute coronary syndrome patients with CHF. The consistent reduction in postdischarge death in revascularized patients suggests that broader application of revascularization in this high-risk group may be beneficial.

Persistent Cardiac Troponin I Elevation in Stabilized Patients After an Episode of Acute Coronary Syndrome Predicts Long-Term Mortality

In patients with non-ST-elevation acute coronary syndrome, any troponin elevation is associated with an increased risk for cardiovascular events. However, the prevalence and prognostic importance of persistent troponin elevation in stabilized patients after an episode of non-ST-elevation acute coronary syndrome are unknown and were therefore assessed in this study. Cardiac troponin I (cTnI) was measured in 1092 stabilized patients at 6 weeks and 3 and 6 months after enrollment in the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC-II) trial. cTnI was analyzed with the Access AccuTnI assay with the application of different prognostic cutoffs. Outcomes were assessed through 5 years. Elevated cTnI levels >0.01 microg/L were found in 48% of the study patients at 6 weeks, in 36% at 6 months, and in 26% at all 3 measurements. cTnI elevation was associated with increased age and other cardiovascular high-risk features. The lowest tested cTnI cutoff (0.01 microg/L) was prognostically most useful and was independently predictive of mortality (hazard ratio, 2.1 [95% confidence interval, 1.3 to 3.3]; P=0.001) on multivariable analysis adjusted for cardiovascular risk factors and randomization to an invasive versus noninvasive treatment strategy, whereas it was related to myocardial infarction only on univariate analysis. Persistent minor cTnI elevation can be detected frequently in patients stabilized after an episode of non-ST-elevation acute coronary syndrome with the use of a sensitive assay. Elevated cTnI levels >0.01 microg/L predict mortality during long-term follow-up. Our results emphasize the importance of further troponin testing in non-ST-elevation acute coronary syndrome patients after hospital discharge.

1313: Management of ST-Elevation Acute Coronary Syndrome Patients. A Nurses' View on the Euro Heart Survey on Acute Coronary Syndromes

1313: Management of ST-Elevation Acute Coronary Syndrome Patients. A Nurses' View on the Euro Heart Survey on Acute Coronary Syndromes