Alogliptin after acute coronary syndrome in patients with type 2 diabetes

Background - To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. Methods - We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results - A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. Conclusions - Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708.)

Effect of age on the prognostic value of left ventricular function in patients with acute coronary syndrome : A prospective registry study

© The European Society of Cardiology 2015. Funding The project was funded by the Sir Halley Stewart Trust. MINAP is funded by the Health Quality Improvement Partnership (HQIP).

Incidentally Raised Cardiac Troponin I Has a Worse Prognosis in Older Patients Compared to Those with Normal Cardiac Troponin I and Patients with Acute Coronary Syndrome : A Cohort Study

Acknowledgement J.H.B.-S. was supported by the Norfolk and Norwich University Hospital (NNUH) Research and Development (R&D) research capability funds between July 2013 and December 2014.

Systemic inflammatory impact of periodontitis on acute coronary syndrome

Aim: A causative relationship between acute coronary syndrome (ACS) and periodontitis has yet to be defined. The aim of this study was to assess differences in levels of serum cytokines between individuals with or without ACS or periodontal comorbidity. Material and Methods: In a case–control study, individuals with ACS (78 individuals, 10.3% females) and matching healthy controls (78 individuals, 28.2% females) were included. Medical and dental examinations were performed to diagnose ACS and periodontitis. Serum levels of cytokines were assessed, using Luminex technology. Results: A diagnosis of periodontitis in the ACS and control group was diagnosed in 52.6% and 12.8% of the individuals, respectively. The unadjusted odds-ratio that individuals with ACS also had periodontitis was 7.5 (95% CI: 3.4, 16.8, p 

Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome.

The mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.

Hypereosinophilic Syndrome Simulating an Acute Coronary Syndrome

Objectives: to report a case of hypereosinophilic syndrome which presented clinically acute coronary syndrome. Materials and methods: we describe a case of a 69-year-old woman with acute coronary syndrome and peripheral hypereosinophilia. Results: the condition rapidly evolved to severe heart failure. Coronary disease was excluded by cardiac catheterization. Systemic corticosteroid therapy was initiated and further secondary causes of hypereosinophilia were excluded.

A Soft Computing Approach to Acute Coronary Syndrome

Acute Coronary Syndrome (ACS) is transversal to a broad and heterogeneous set of human beings, and assumed as a serious diagnosis and risk stratification problem. Although one may be faced with or had at his disposition different tools as biomarkers for the diagnosis and prognosis of ACS, they have to be previously evaluated and validated in different scenarios and patient cohorts. Besides ensuring that a diagnosis is correct, attention should also be directed to ensure that therapies are either correctly or safely applied. Indeed, this work will focus on the development of a diagnosis decision support system in terms of its knowledge representation and reasoning mechanisms, given here in terms of a formal framework based on Logic Programming, complemented with a problem solving methodology to computing anchored on Artificial Neural Networks. On the one hand it caters for the evaluation of ACS predisposing risk and the respective Degree-of-Confidence that one has on such a happening. On the other hand it may be seen as a major development on the Multi-Value Logics to understand things and ones behavior. Undeniably, the proposed model allows for an improvement of the diagnosis process, classifying properly the patients that presented the pathology (sensitivity ranging from 89.7% to 90.9%) as well as classifying the absence of ACS (specificity ranging from 88.4% to 90.2%).

Comparison of high sensitivity troponin T and I assays in the diagnosis of non-ST elevation acute myocardial infarction in emergency patients with chest pain

Objectives: Concentrations of troponin measured with high sensitivity troponin assays are raised in a number of emergency department (ED) patients; however many are not diagnosed with acute myocardial infarction (AMI). Clinical comparisons between the early use (2 h after presentation) of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) assays for the diagnosis of AMI have not been reported. Design and methods: Early (0 h and 2 h) hs-cTnT and hs-cTnI assay results in 1571 ED patients with potential acute coronary syndrome (ACS) without ST elevation on electrocardiograph (ECG) were evaluated. The primary outcome was diagnosis of index MI adjudicated by cardiologists using the local cTnI assay results taken ≥6 h after presentation, ECGs and clinical information. Stored samples were later analysed with hs-cTnT and hs-cTnI assays. Results: The ROC analysis for AMI (204 patients; 13.0%) for hs-cTnT and hs-cTnI after 2 h was 0.95 (95% CI: 0.94–0.97) and 0.98 (95% CI: 0.97–0.99) respectively. The sensitivity, specificity, PLR, and NLR of hs-cTnT and hs-cTnI for AMI after 2 h were 94.1% (95% CI: 90.0–96.6) and 95.6% (95% CI: 91.8–97.7), 79.0% (95% CI: 76.8–81.1) and 92.5% (95% CI: 90.9–93.7), 4.48 (95% CI: 4.02–5.00) and 12.86 (95% CI: 10.51–15.31), and 0.07 (95% CI: 0.04–0.13) and 0.05 (95% CI:0.03–0.09) respectively. Conclusions: Exclusion of AMI 2 h after presentation in emergency patients with possible ACS can be achieved using hs-cTnT or hs-cTnI assays. Significant differences in specificity of these assays are relevant and if using the hs-cTnT assay, further clinical assessment in a larger proportion of patients would be required.

Association of increasing age with receipt of specialist care and long-term mortality in patients with non-ST elevation myocardial infarction

© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

Bridging Knowledge Gaps in the Management of Acute Coronary Syndromes

Contexte L’occlusion d’une artère du cœur cause un syndrome coronarien aigu (SCA) soit avec une élévation du segment ST (IAMEST) ou sans élévation du segment ST (1). Le traitement des patients avec un IAMEST requiert soit une intervention coronarienne d’urgence (ICP primaire) ou une thérapie fibrinolytique (FL). La thérapie FL peut être administrée soit dans un contexte pré-hospitalier (PHL) ou à l’hôpital. Une prise en charge précoce des patients avec SCA peut être améliorée par un simple indice de risque. Objectifs Les objectifs de cette thèse étaient de : 1) comparer l’ICP primaire et la thérapie FL (2); décrire plusieurs systèmes internationaux de PHL; (3) développer et valider un indice de risque simplifié pour une stratification précoce des patients avec SCA. Méthodes Nous complétons des méta-analyses, de type hiérarchique Bayésiennes portant sur l’effet de la randomisation, d’études randomisées et observationnelles; complétons également un sondage sur des systèmes internationaux de PHL; développons et validons un nouvel indice de risque pour ACS (le C-ACS). Résultats Dans les études observationnelles, l’ICP primaire, comparée à la thérapie FL, est associée à une plus grande réduction de la mortalité à court-terme; mais ce sans bénéfices concluants à long terme. La FL pré-hospitalière peut être administrée par des professionnels de la santé possédant diverses expertises. Le C-ACS a des bonnes propriétés discriminatoires et pourrait être utilisé dans la stratification des patients avec SCA. Conclusion Nous avons comblé plusieurs lacunes importantes au niveau de la connaissance actuelle. Cette thèse de doctorat contribuera à améliorer l’accès à des soins de qualité élevée pour les patients ayant un SCA.

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.

Invasive coronary treatment strategies for out-of-hospital cardiac arrest: a consensus statement from the European association for percutaneous cardiovascular interventions (EAPCI)/stent for life (SFL) groups

Due to significant improvement in the pre-hospital treatment of patients with out-of-hospital cardiac arrest (OHCA), an increasing number of initially resuscitated patients are being admitted to hospitals. Because of the limited data available and lack of clear guideline recommendations, experts from the EAPCI and "Stent for Life" (SFL) groups reviewed existing literature and provided practical guidelines on selection of patients for immediate coronary angiography (CAG), PCI strategy, concomitant antiplatelet/anticoagulation treatment, haemodynamic support and use of therapeutic hypothermia. Conscious survivors of OHCA with suspected acute coronary syndrome (ACS) should be treated according to recommendations for ST-segment elevation myocardial infarction (STEMI) and high-risk non-ST-segment elevation -ACS (NSTE-ACS) without OHCA and should undergo immediate (if STEMI) or rapid (less than two hours if NSTE-ACS) coronary invasive strategy. Comatose survivors of OHCA with ECG criteria for STEMI on the post-resuscitation ECG should be admitted directly to the catheterisation laboratory. For patients without STEMI ECG criteria, a short "emergency department or intensive care unit stop" is advised to exclude non-coronary causes. In the absence of an obvious non-coronary cause, CAG should be performed as soon as possible (less than two hours), in particular in haemodynamically unstable patients. Immediate PCI should be mainly directed towards the culprit lesion if identified. Interventional cardiologists should become an essential part of the "survival chain" for patients with OHCA. There is a need to centralise the care of patients with OHCA to experienced centres.