Efficacy and safety of thrombin-receptor antagonist (atopaxar and vorapaxar) in patients with acute coronary syndrome or coronary artery disease-a meta-analysis of randomized controlled trials

Background: Meta-analysis for the efficacy and safety data of thrombin-receptor antagonist (TRA) based on patients with acute coronary syndrome (ACS) or coronary artery disease (CAD) and indirect comparisons between TRAs were not available. Objectives: We intended to synthesize the primary end points based on different patient populations (ACS or CAD) as well as perform indirect comparison between two newly invented antiplatelet agents atopaxar and vorapaxar. Methods: A literature search was performed in MEDLINE, Embase, and Cochrane Library. Incidences of major adverse cardiovascular events (MACEs) and bleeding events according to thrombolysis in myocardial infarction were selected as primary outcomes, whereas adverse effects were considered as secondary outcomes. Corresponding results were synthesized using Revman 5.1 according to ACS or CAD cohorts. Results: Among the seven included randomized controlled trials, the efficacy end points in the TRA treatment group were favorable compared with placebo. Specifically, the odds ratio (OR) of MACEs was 0.80 (95% confidence interval [CI] 0.52-1.22) for patients with ACS and 0.74 (95% CI 0.53-1.05) for the cohort with CAD. The events of bleeding were unanimously superior in the placebo arm for both cohorts. The indirect comparison showed a superior trend in favor of atopaxar over vorapaxar in occurrences of MACEs (OR 0.93; 95% CI 0.38-1.32), myocardial infarction (OR 0.52; 95% CI 0.13-0.95), and cardiovascular death (OR 0.82; 95% CI 0.12-4.24) and caused less incidence of bleeding. Conclusions: Besides being more effective than placebo in improving the incidence of MACEs but with a higher risk of bleeding, TRAs may exert different effects in patients with ACS and CAD. Indirect comparisons also suggested that atopaxar might be better than vorapaxar in lowering the incidence of MACEs, myocardial infarction, and cardiovascular death and at the same time with lower risks of bleeding.

Lifestyle pattern change in males following percutaneous transluminal coronary angioplasty/intracoronary stenting

tilizing a naturalistic inquiry approach, a semi-structured interview schedule and non-probability purposive sampling, this study provided detail on the rationale and influences behind the decisions of four males participants to change or not change their lifestyle patterns 3 months after a percutaneous transluminal coronary angioplasty/intracoronary stent procedure. One of the participants made a noticeable lifestyle pattern change in this period. The remaining participants failed to exhibit any discernible lifestyle pattern change or had continued with their previous behaviours. Results suggest a new 'positive' psychological health perspective, family considerations, return-to-work issues and a reluctance to participate in cardiac rehabilitation as the major factors influencing lifestyle pattern change. Because nurses spend the greatest amount of time with percutaneous transluminal coronary angioplasty/intracoronary stent patients during hospitalization, they have the best opportunity to provide up-to-date and relevant information to patients that will enable them to then make decisions concerning cardiac healthy lifestyle changes.

Identifying the health and mental health information needs of people with coronary heart disease, with and without depression

Objective:
To identify the health and mental health information needs of people with coronary heart disease (CHD), with and without comorbid depression.

Design and setting:
A qualitative study conducted in Melbourne in 2006, using thematic analysis of semi-structured interviews on the types of health information that patients with CHD considered useful to assist with the management of their illness. Structured clinical interviews were used to assess current and prior depressive episodes in these patients.

Participants:
14 general practice patients (eight with current or prior history of major depression) who had experienced myocardial infarction, coronary artery bypass graft surgery, angioplasty or angina (confirmed via testing).

Results:
Four themes relating to information on how patients could manage their cardiovascular health and improve their psychosocial wellbeing emerged: psychosocial; physical activity; medical; and information for family. The most prominent information needs included identification and management of risk-related physical symptoms, and psychosocial information, most notably to enhance patients’ social support. Patients considered this information important for alleviating health anxiety and negative affect.

Conclusion:
This small patient sample endorsed the need for health and mental health information on a range of psychosocial and physical health topics. Participants desired specific types of information to assist with the self-management of their health and to assuage their health concerns.

Screening, referral and treatment for depression in patients with coronary heart disease: a consensus statement from the National Heart Foundation of Australia

In 2003, the National Heart Foundation of Australia position statement on “stress” and heart disease found that depression was an important risk factor for coronary heart disease (CHD). This 2013 statement updates the evidence on depression (mild, moderate and severe) in patients with CHD, and provides guidance for health professionals on screening and treatment for depression in patients with CHD.

The prevalence of depression is high in patients with CHD and it has a significant impact on the patient’s quality of life and adherence to therapy, and an independent effect on prognosis. Rates of major depressive disorder of around 15% have been reported in patients after myocardial infarction or coronary artery bypass grafting.

To provide the best possible care, it is important to recognise depression in patients with CHD. Routine screening for depression in all patients with CHD is indicated at first presentation, and again at the next follow-up appointment. A follow-up screen should occur 2–3 months after a CHD event. Screening should then be considered on a yearly basis, as for any other major risk factor for CHD.

A simple tool for initial screening, such as the Patient Health Questionnaire-2 (PHQ-2) or the short-form Cardiac Depression Scale (CDS), can be incorporated into usual clinical practice with minimum interference, and may increase uptake of screening.

Patients with positive screening results may need further evaluation. Appropriate treatment should be commenced, and the patient monitored. If screening is followed by comprehensive care, depression outcomes are likely to be improved.

Patients with CHD and depression respond to cognitive behaviour therapy, collaborative care, exercise and some drug therapies in a similar way to the general population. However, tricyclic antidepressant drugs may worsen CHD outcomes and should be avoided.

Coordination of care between health care providers is essential for optimal outcomes for patients. The benefits of treating depression include improved quality of life, improved adherence to other therapies and, potentially, improved CHD outcomes.

Impact of high-sensitivity cardiac troponin I assays on patients presenting to an emergency department with suspected acute coronary syndrome

 Objective: To determine whether introduction of high-sensitivity cardiac troponin I (hscTn-I) assays aff ected management of patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary referral hospital. Design, patients and setting: A retrospective analysis of all patients presenting to the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I assays on 23 April 2012. Main outcome measures: Hospital admission rates, time spent in the ED, rates of coronary angiography, rates of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosis of ACS, and rates of inhospital mortality. Results: 12 360 consecutive patients presented with suspected ACS during the study period; 1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1 year after the changeover to hscTn-I assays. Comparing the two patient groups, there was no statistically signifi cant diff erence in allhospital admission rates (95% CI for the diff erence, - 3.1% to 0.3%; P = 0.10) or proportion of patients subsequently discharged with a diagnosis of ACS (95% CI for the diff erence, - 2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the diff erence, - 0.59 to - 0.43; P < 0.001) and the proportion of admitted patients undergoing coronary angiography was higher (53.4% v 45.2%; 95% CI for the diff erence, 4.3 to 12.0 percentage points; P < 0.001), but there was no statistically signifi cant rise in the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI for the diff erence, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from ACS did not change signifi cantly (95% CI for the diff erence, - 1.5% to 0.8%; P = 0.43). Conclusion: The introduction of hscTn-I assays appeared to be associated with more rapid diagnosis, resulting in less time spent in the ED, without a change in hospital admission rates. A higher proportion of patients had coronary angiographies after the changeover, but there was no signifi cant change in rates of invasive treatment or inhospital mortality.

Novel therapeutics for cononary artery disease from genome-wide association study data

Abstract
Background: Coronary artery disease (CAD), one of the leading causes of death globally, is influenced by both environmental and genetic risk factors. Gene-centric genome-wide association studies (GWAS) involving cases and controls have been remarkably successful in identifying genetic loci contributing to CAD. Modern in silico platforms, such as candidate gene prediction tools, permit a systematic analysis of GWAS data to identify candidate genes for complex diseases like CAD. Subsequent integration of drug-target data from drug databases with the predicted candidate genes can potentially identify novel therapeutics suitable for repositioning towards treatment of CAD.
Methods: Previously, we were able to predict 264 candidate genes and 104 potential therapeutic targets for CAD using Gentrepid (www.gentrepid.org), a candidate gene prediction platform with two bioinformatic modules to reanalyze Wellcome Trust Case-Control Consortium GWAS data. In an expanded study, using five bioinformatics modules on the same data, Gentrepid predicted 647 candidate genes and successfully replicated 55% of the candidate genes identified by the more powerful CARDIoGRAMplusC4D consortium meta-analysis. Hence, Gentrepid was capable of enhancing lower quality genotype-phenotype data, using an independent knowledgebase of existing biological data. Here, we used our methodology to integrate drug data from three drug databases: the Therapeutic Target Database, PharmGKB and Drug Bank, with the 647 candidate gene predictions from Gentrepid. We utilized known CAD targets, the scientific literature, existing drug data and the CARDIoGRAMplusC4D meta-analysis study as benchmarks to validate Gentrepid predictions for CAD.
Results: Our analysis identified a total of 184 predicted candidate genes as novel therapeutic targets for CAD, and 981 novel therapeutics feasible for repositioning in clinical trials towards treatment of CAD. The benchmarks based on known CAD targets and the scientific literature showed that our results were significant (p < 0.05).
Conclusions: We have demonstrated that available drugs may potentially be repositioned as novel therapeutics for the treatment of CAD. Drug repositioning can save valuable time and money spent on preclinical and phase I clinical studies.

Gender differences in presentation, coronary intervention, and outcomes of 28,985 acute coronary syndrome patients in Victoria, Australia

BACKGROUND: Differences in demographics, presenting characteristics, and treatment of heart disease in women may contribute to adverse outcomes. The purpose of this paper was to describe gender differences in the epidemiology, treatment, and outcomes of all admissions for acute coronary syndrome (ACS) in Victoria that occurred between June 2007 and July 2009. METHODS: We undertook a retrospective cohort study of all patients admitted to Victorian hospitals with a first time diagnosis of ACS. Use of angiograms, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and adverse outcomes (death and/or unplanned readmission) were compared by gender and hierarchical logistic regression models were used to account for confounding variables. RESULTS: Of a total of 28,985 ACS patients, 10,455 (36%) were women. Compared with men, women were older (aged ≥75 years: 54% vs 31%; p < .001), more likely to present with multiple comorbidities (>1 comorbidity: 53% vs 46%; p < .001), and more likely to be diagnosed with non-ST-segment elevation ACS (86% vs 80%; p < .001). Women were less likely to receive coronary interventions (angiogram: adjusted odds ratio [aOR], 0.71; 95% CI, 0.66-0.75; PCI: aOR, 0.73; 95% CI, 0.66-0.80; CABG: aOR, 0.58; 95% CI, 0.53-0.64). Adverse outcomes were similar in women and men after accounting for confounding variables. CONCLUSIONS: Our results show that women in Victoria were less likely to receive coronary interventions after an admission for ACS. Clinicians should be wary of inherent gender bias in decisions to refer patients for angiography.

Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice

Postoperative pulmonary complications are the most frequent and significant contributor to morbidity, mortality, and costs associated with hospitalization. Interestingly, despite the prevalence of these complications in cardiac surgical patients, recognition, diagnosis, and management of this problem vary widely. In addition, little information is available on the continuum between routine postoperative pulmonary dysfunction and postoperative pulmonary complications. The course of events from pulmonary dysfunction associated with surgery to discharge from the hospital in cardiac patients is largely unexplored. In the absence of evidence-based practice guidelines for the care of cardiac surgical patients with postoperative pulmonary dysfunction, an understanding of the path ophysiological basis of the development of postoperative pulmonary complications is fundamental to enable clinicians to assess the value of current management interventions. Previous research on postoperative pulmonary dysfunction in adults undergoing cardiac surgery is reviewed, with an emphasis on the pathogenesis of this problem, implications for clinical nursing practice, and possibilities for future research.

Ischaemic heart disease and Australian immigrants: the influence of birthplace and language skills on treatment and use of health services

Admission rates for ischaemic heart disease (IHD), and the use of invasive cardiovascular procedures, separation mode and length of stay (LOS) were compared between Australians from non-English speaking background (NESB; n=8627) and English speaking background (ESB; n=13162) aged 20 years and over admitted to Victorian urban public hospitals. The study covered the period from 1993 to 1998. It was found that, compared with their ESB counterparts, the incidence of admission for acute myocardial infarction was significantly higher for NESB men and women before and after controlling for confounding factors. The age-adjusted ratios for NESB women compared with their ESB counterparts ranged from 1.23 to 1.89 for cardiac catheterisation, from 0.23 to 0.27 for percutaneous transluminal coronary angioplasty (PTCA), and from 1.04 to 1.80 for coronary artery bypass grafting (CABG).
Procedure rates were comparable in men for cardiac catheterisation and CABG but higher for PTA rates in NESB men (OR: 1.29, 95%CI: 1.11-1.50) than their ESB counterparts. Both NESB men (β=0.04, 95%CI: 0.01-0.07) and women (β=0.03, 95%CI: 0.02-0.08) experienced significantly longer hospital stays than their ESB counterparts. These findings indicate there may be systematic differences in patients’ treatment and service utilisation in Victorian public hospitals. The extent to which physicians’ bias and
patients’ choice could explain these differences requires further investigation.

Psychosocial issues facilitating recovery post-CABG surgery

Background
The acute illness phase following coronary artery bypass graft (CABG) surgery is a difficult time for patients as they try to adjust to the physical and emotional changes brought about by surgery.
Aims
To conduct an indepth examination of psychosocial issues experienced by patients post-CABG surgery and how patients manage these psychosocial issues during their recovery.
Methods
A qualitative research approach, naturalistic inquiry, guided the study. Thirty patients were interviewed 4–5 weeks following discharge from hospital after CABG surgery and at 12 months after the initial interview.
Results
esults found that adjusting to life after surgery was difficult, and patients experienced some form of physical pain or change. An unexpected finding was the extent to which many of the patients were attuned to their post-operative physical adjustments. Patients spoke of mental and emotional changes, and coming to terms with lifestyle adjustments.
Conclusion
Study findings suggest the need for a re-examination of hospital discharge preparation and further provision and monitoring of home support services.

Variable definitions: implications for the prediction of pulmonary complications after adult cardiac surgery

Aim: The aim of this paper was to review the implications that variable definitions have for the prediction of post-operative pulmonary complications after cardiac surgery.

Method: A review of the literature from 1980 to 2002. Selected studies demonstrated an original attempt to examine multivariate associations between pre, intra or post-operative antecedents and pulmonary outcomes in patients undergoing coronary artery bypass grafting (CABG). Reports that described the validation of established clinical prediction rules, testing interventions or research conducted in non-human cohorts were excluded from this review.

Results: Consistently, variable factor and outcome definitions are combined for the development of multivariate prediction models that subsequently have limited clinical value. Despite being prevalent there are very few attempts to examine post-operative pulmonary complications (PPC) as endpoints in isolation. The trajectory of pulmonary dysfunction that precedes complications in the post-operative context is not clear. As such there is little knowledge of post-operative antecedents to PPC that are invariably excluded from model development.

Conclusion: Multivariate clinical prediction rules that incorporate antecedent patient and process factors from the continuum of cardiovascular care for specific pulmonary outcomes are recommended. Models such as these would be useful for practice, policy and quality improvement.

Outpatient cardiac rehabilitation attendance in England

Abstract
PURPOSE:
Cardiac rehabilitation is an effective but underprovided treatment for patients recovering from acute cardiac events. The geographical spread of provision has not been investigated recently in any country. This study aimed to investigate the level of participation in cardiac rehabilitation programs of patients following myocardial infarction or revascularization (eligible patients) and the geographical equity of attendance.
METHODS:
Questionnaire data were collected from all cardiac rehabilitation centers in England for the year 2003/2004. The number of patients attending rehabilitation was compared with eligible patients across the 9 Government Office Regions of England as indicated by Hospital Episode Statistics.
RESULTS:
Nationally, 29% of eligible patients attended rehabilitation, while within various regions, the proportion of eligible patients participating in rehabilitation ranged between 14% (95% CI, 13.2-14.3) and 37% (95% CI, 36.6-37.6). Participation also differed significantly by primary cardiac event: myocardial infarction, 25%; percutaneous coronary intervention, 24%; and coronary artery bypass surgery, 66% (P < .001).
CONCLUSION:
The participation rate of eligible patients in cardiac rehabilitation was low in all regions. There were large differences between regions with widely varying incidence of attendance in different parts of the country.

Recent advances on the roles of NO in cancer and chronic inflammatory disorders

Nitric oxide (NO) is a short-life molecule produced by the enzyme known as the nitric oxide synthase (NOS), in a reaction that converts arginine and oxygen into citrulline and NO. There are three isoforms of the enzyme: neuronal NOS (nNOS, also called NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3). It is now known that each of these isoforms may be expressed in a variety of tissues and cell types. This paper is a review of the current knowledge of various functions of NO in diseases. We discuss in more detail its role in Cancer, the role of NO in myocardial pathophysiology, in central nervous system (CNS) pathologies. Other diseases such as inflammation, asthma, in chronic liver diseases, inflammatory bowel disease (IBD), arthritis, are also discussed. This review also covers the role of NO in cardiovascular, central nervous, pancreas, lung, gut, kidney, myoskeletal and chronic liver diseases (CLD). The ubiquitous role that the simple gas nitric oxide plays in the body, from maintaining vascular homeostasis and fighting infections to acting as a neurotransmitter and its role in cancer, has spurred a lot of interest among researchers all over the world. Nitric oxide plays an important role in the physiologic modulation of coronary artery tone and myocardial function. Nitric oxide from iNOS appears to be a key mediator of such glial-induced neuronal death. The high sensitivity of neurons to NO is partly due to NO causing inhibition of respiration, rapid glutamate release from both astrocytes and neurons, and subsequent excitotoxic death of the neurons.