High-risk NSTE-ACS: high time for robust data.
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ABSTRACT:
SUBMITTER: Kite TA
PROVIDER: S-EPMC7850134 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionNon-ST-segment elevation acute coronary syndromes (NSTE ACS) are highly prevalent in the United States and globally, and are associated with significant morbidity and mortality.DiscussionThe key role of platelet-mediated thrombosis in the pathogenesis of NSTE ACS is confirmed by the proven clinical benefits of antiplatelet agents (aspirin and a P2Y(12) adenosine diphosphate [ADP] receptor antagonist) in this setting. Despite the documented advantages and broad use of antiplatelet therapy, the long-term morbidity and mortality rates remain significant, and the bleeding risk remains substantial. Residual risk can be attributed, at least in part, to the fact that thrombosis continues in the presence of current treatments because aspirin and P2Y(12) ADP receptor antagonists each block only one of multiple platelet activation pathways, and thus do not impact other platelet activation pathways, such as the one triggered by interaction of thrombin with protease-activated receptor (PAR)-1, thereby exposing patients to continued accumulation of thrombotic events.ConclusionThese considerations suggest that novel therapies with a different mechanism of action, when used in combination with current antiplatelet agents, may provide more comprehensive inhibition of platelet activation and additional reductions in morbidity and mortality, potentially without incremental bleeding risk.
| S-EPMC2797418 | biostudies-literature
Project description:BackgroundResults from randomized controlled trials (RCTs) and meta-analyses comparing invasive and conservative strategies in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are highly debatable. We systematically evaluate the efficacy of invasive and conservative strategies in NSTE-ACS based on time-varied outcomes.MethodsThe RCTs for the invasive versus conservative strategies were identified by searching PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov. Trial data for studies with a minimum follow-up time of 30 days were included. We categorized the follow-up time into six varied periods, namely, ≤6 months, 1 year, 2 years, 3 years, 5 years, and ≥10 years. The time-varied outcomes were major adverse cardiovascular event (MACE), death, myocardial infarction (MI), rehospitalization, cardiovascular death, bleeding, in-hospital death, and in-hospital bleeding. Risk ratios (RRs) and 95% confidence intervals (Cis) were calculated. The random effects model was used.ResultsThis meta-analysis included 30 articles of 17 RCTs involving 12,331 participants. We found that the invasive strategy did not provide appreciable benefits for NSTE-ACS in terms of MACE, death, and cardiovascular death at all time points compared with the conservative strategy. Although the risk of MI was reduced within 6 months (RR 0.80, 95% CI 0.68-0.94) for the invasive strategy, no significant differences were observed in other periods. The invasive strategy reduced the rehospitalization rate within 6 months (RR 0.69, 95% CI 0.52-0.90), 1 year (RR 0.73, 95% CI 0.63-0.86), and 2 years (RR 0.77, 95% CI 0.60-1.00). Of note, an increased risk of bleeding (RR 1.80, 95% CI 1.28-2.54) and in-hospital bleeding (RR 2.17, 95% CI 1.52-3.10) was observed for the invasive strategy within 6 months. In subgroups stratified by high-risk features, the invasive strategy decreased MACE for patients aged ≥65 years within 6 months (RR 0.68, 95% CI 0.58-0.78) and 1 year (RR 0.75, 95% CI 0.62-0.91) and showed benefits for men within 6 months (RR 0.71, 95% CI 0.55-0.92). In other subgroups stratified according to diabetes, ST-segment deviation, and troponin levels, no significant differences were observed between the two strategies.ConclusionsAn invasive strategy is superior to a conservative strategy in reducing early events for MI and rehospitalizations, but the invasive strategy did not improve the prognosis in long-term outcomes for patients with NSTE-ACS.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289579, identifier PROSPERO 2021 CRD42021289579.
| S-EPMC10516546 | biostudies-literature
Project description:BackgroundThere are no studies comparing single-session vs staged multivessel intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) or non-ST-segment-elevation acute coronary syndrome (NSTE-ACS).ObjectivesThe authors aimed to compare single-session vs staged multivessel IVUS-guided PCI in patients with CCS or NSTE-ACS.MethodsThe OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1,021 patients with CCS or NSTE-ACS undergoing multivessel PCI including left anterior descending coronary artery using IVUS aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared single-session vs staged multivessel PCI. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization.ResultsThere were 246 patients (24.1%) undergoing single-session multivessel PCI, and 775 patients (75.9%) undergoing staged multivessel PCI. There was a wide variation in the prevalence of single-session multivessel PCI across the participating centers. The staged multivessel PCI group more often had complex coronary anatomy such as 3-vessel disease, chronic total occlusion, and calcified lesions requiring an atherectomy device compared with the single-session multivessel PCI group. The rates of PCI success, procedural complications, and meeting OPTIVUS criteria were not different between groups. The cumulative 1-year incidence of the primary endpoint was not different between single-session and staged multivessel PCI groups (9.0% vs 10.8%, log-rank P = 0.42). After adjusting confounders, the effect of single-session multivessel PCI relative to staged multivessel PCI was not significant for the primary endpoint (HR: 0.95; 95% CI: 0.58-1.55; P = 0.84).ConclusionsSingle-session and staged multivessel IVUS-guided PCI had similar 1-year outcomes.
| S-EPMC10442883 | biostudies-literature
Project description:BackgroundIn the era of High-sensitive troponin (hs-Tn), up to 50% of patients with a mild increase of hs-Tn will finally have a normal invasive coronary angiogram. Fractional Flow Reserve (FFR) derived from coronary computed tomographic angiography (FFR-CT) has never been used as a non-invasive tool for the diagnosis of coronary artery disease in patients with high-risk acute coronary syndrome without ST segment elevation (NSTE-ACS).AimsThe study aims to determine the role of coronary CT angiography and FFR-CT in the setting of high-risk NSTE-ACS.MethodologyWe will conduct a prospective trial, enrolling 250 patients admitted with high-risk NSTE-ACS who will rapidly undergo a coronary CT angiography and then a coronary angiography with FFR measurements. Results of coronary CT, FFR-CT and coronary angiography (± FFR) will be compared.Potential significanceIn conclusion, non-invasive identification of patients with high-risk NSTE-ACS who could avoid coronary angiography would reduce procedure related risks and medical costs.
| S-EPMC7063126 | biostudies-literature
Project description:There are no randomised data on which antiplatelet agent to use in elderly patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and an indication for oral anticoagulation (OAC). The randomised POPular Age trial, in patients of 70 years or older with NSTE-ACS, showed a reduction in bleeding without increasing thrombotic events in patients using clopidogrel as compared to ticagrelor. In this sub-analysis of the POPular AGE trial, we compare clopidogrel with ticagrelor in patients with a need for oral anticoagulation. The follow-up duration was one year. The primary bleeding outcome was Platelet Inhibition and Patient Outcomes (PLATO) major and minor bleeding. The primary thrombotic outcome consisted of cardiovascular death, myocardial infarction and stroke. The primary net clinical benefit outcome was a composite of all-cause death, myocardial infarction, stroke, and PLATO major and minor bleeding. A total of 184/1011 (18.2%) patients on OAC were included in this subanalysis; 83 were randomized to clopidogrel and 101 to ticagrelor. The primary bleeding outcome was lower in the clopidogrel group (17/83, 20.9%) compared to the ticagrelor group (33/101, 33.5%; p = 0.051), as was the thrombotic outcome (7/83, 8.4% vs. 19/101, 19.2%; p = 0.035) and the primary net clinical benefit outcome (23/83, 27.7% vs. 49/101, 48.5%; p = 0.003). In this subgroup of patients using OAC, clopidogrel reduced PLATO major and minor bleeding compared to ticagrelor without increasing thrombotic risk. This analysis therefore suggests that, in line with the POPular Age trial, clopidogrel is a better option than ticagrelor in NSTE-ACS patients ≥70 years using OAC.
| S-EPMC7601891 | biostudies-literature
Project description:The timing of coronary angiography in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) remains a matter of debate. The relationship between the timing of invasive management and left ventricular function (LVF) is largely unknown. The An Immediate or Early Invasive Strategy in Non-ST-Elevation Acute Coronary Syndrome trial (OPTIMA-2) was a randomized controlled prospective open-label multicenter trial that randomized 249 NSTE-ACS patients to either an immediate (<3 h) invasive treatment strategy or an early strategy (12-24 h). Patients were pre-treated with a combination of aspirin, ticagrelor and fondaparinux. The aim of this prespecified sub-analysis was to assess (the recovery of) left ventricular function by analysing echocardiography data obtained <72 h after admission and at 30-day follow-up, for patients with a confirmed diagnosis of acute coronary syndrome. LVF was determined using ejection fraction (EF) and global longitudinal strain (GLS). Inter-observer variability was tested. No difference in the recovery of EF was found between an immediate and early strategy if the follow-up echocardiograms were compared to baseline: 2.5% (standard deviation (SD): 7.9) and 3.3% (SD: 8.5), p = 0.51, nor was there any difference in GLS recovery between the study groups: -0.8% (SD: 2.5) vs. -0.7% (SD 2.8) p = 0.82. If baseline and follow-up echocardiograms were compared, there was a similar but significant improvement in both EF and GLS in both separate study groups. An immediate invasive strategy in NSTE-ACS patients did not result in an improved left ventricular EF or GLS recovery compared with an early strategy.
| S-EPMC8396935 | biostudies-literature
Project description:BackgroundIn light of overlapping symptoms, discrimination between non-ST-elevation (NSTE) acute coronary syndrome (ACS) and acute heart failure (HF) is challenging, particularly in patients with equivocal clinical presentation for suspected ACS. We sought to evaluate the diagnostic and prognostic properties of copeptin in this scenario.MethodsData from 1088 patients from a single-center observational registry were used to test the ability of serial high sensitivity cardiac troponin T (hs-cTnT)-compared to copeptin, or a combination of copeptin with hs-cTnT-to discriminate acute HF from uncomplicated non-ST-elevation myocardial infarction (NSTEMI) and to evaluate all-cause mortality after 365 days. Patients with STEMI, those with unstable angina and either normal or undetectable hs-cTnT concentrations were excluded. The findings were validated in an independent external NSTE-ACS cohort.ResultsA total of 219 patients were included in the analysis. The final diagnosis was acute HF in 56 and NSTE-ACS in 163, with NSTEMI in 78 and unstable angina having stable elevation of hs-cTnT >ULN in 85. The rate of all-cause death at 1 year was 9.6% and occurred significantly more often in acute HF than in NSTE-ACS (15 vs. 6%, p < 0.001). In the test cohort, the area under the receiver operator curve (AUC) for the discrimination of acute HF vs. NSTE-ACS without HF was 0.725 (95% confidence interval [CI] 0.625-0.798) for copeptin and significantly higher than for hs-cTnT at 0 h (AUC = 0.460, 0.370-0.550) or at 3 h (AUC = 0.441, 0.343-0.538). Copeptin and hs-cTnT used either as continuous values or at cutoffs optimized to yield 90% specificity for acute HF were associated with significantly higher age- and sex-adjusted risk for all-cause mortality at 365 days. The findings from the test cohort were consistently replicated in the independent external NSTE-ACS validation cohort.ConclusionsHigh concentrations of copeptin in patients with suspected NSTE-ACS and equivocal clinical presentation suggest the presence of acute HF compared to uncomplicated NSTE-ACS and are associated with higher rates of all-cause death at 365 days.
| S-EPMC10092967 | biostudies-literature
Project description:Quantitative high throughput screening (qHTS) assays use cells or tissues to screen thousands of compounds in a short period of time. Data generated from qHTS assays are then evaluated using nonlinear regression models, such as the Hill model, and decisions regarding toxicity are made using the estimates of the parameters of the model. For any given compound, the variability in the observed response may either be constant across dose groups (homoscedasticity) or vary with dose (heteroscedasticity). Since thousands of compounds are simultaneously evaluated in a qHTS assay, it is not practically feasible for an investigator to perform residual analysis to determine the variance structure before performing statistical inferences on each compound. Since it is well-known that the variance structure plays an important role in the analysis of linear and nonlinear regression models it is therefore important to have practically useful and easy to interpret methodology which is robust to the variance structure. Furthermore, given the number of chemicals that are investigated in the qHTS assay, outliers and influential observations are not uncommon. In this article we describe preliminary test estimation (PTE) based methodology which is robust to the variance structure as well as any potential outliers and influential observations. Performance of the proposed methodology is evaluated in terms of false discovery rate (FDR) and power using a simulation study mimicking a real qHTS data. Of the two methods currently in use, our simulations studies suggest that one is extremely conservative with very small power in comparison to the proposed PTE based method whereas the other method is very liberal. In contrast, the proposed PTE based methodology achieves a better control of FDR while maintaining good power. The proposed methodology is illustrated using a data set obtained from the National Toxicology Program (NTP). Additional information, simulation results, data and computer code are available online as supplementary materials.
| S-EPMC3727440 | biostudies-literature
Project description:BackgroundMean-based clustering algorithms such as bisecting k-means generally lack robustness. Although componentwise median is a more robust alternative, it can be a poor center representative for high dimensional data. We need a new algorithm that is robust and works well in high dimensional data sets e.g. gene expression data.ResultsHere we propose a new robust divisive clustering algorithm, the bisecting k-spatialMedian, based on the statistical spatial depth. A new subcluster selection rule, Relative Average Depth, is also introduced. We demonstrate that the proposed clustering algorithm outperforms the componentwise-median-based bisecting k-median algorithm for high dimension and low sample size (HDLSS) data via applications of the algorithms on two real HDLSS gene expression data sets. When further applied on noisy real data sets, the proposed algorithm compares favorably in terms of robustness with the componentwise-median-based bisecting k-median algorithm.ConclusionStatistical data depths provide an alternative way to find the "center" of multivariate data sets and are useful and robust for clustering.
| S-EPMC2099500 | biostudies-literature
Project description:Single-cell gene expression data provide invaluable resources for systematic characterization of cellular hierarchy in multi-cellular organisms. However, cell lineage reconstruction is still often associated with significant uncertainty due to technological constraints. Such uncertainties have not been taken into account in current methods. We present ECLAIR (Ensemble Cell Lineage Analysis with Improved Robustness), a novel computational method for the statistical inference of cell lineage relationships from single-cell gene expression data. ECLAIR uses an ensemble approach to improve the robustness of lineage predictions, and provides a quantitative estimate of the uncertainty of lineage branchings. We show that the application of ECLAIR to published datasets successfully reconstructs known lineage relationships and significantly improves the robustness of predictions. ECLAIR is a powerful bioinformatics tool for single-cell data analysis. It can be used for robust lineage reconstruction with quantitative estimate of prediction accuracy.
| S-EPMC5001598 | biostudies-literature