Early invasive versus conservative strategies for unstable angina & non-ST-elevation myocardial infarction in the stent era (Review)

BACKGROUND: In patients with unstable angina and non-ST-elevation myocardial infarction (UA/NSTEMI) two strategies are possible: a routine invasive strategy where all patients undergo coronary angiography shortly after admission and, if indicated, coronary revascularization; or a conservative strategy where medical therapy alone is used initially with selection of patients for angiography based on clinical symptoms or investigational evidence of persistent myocardial ischemia. OBJECTIVES: To determine the benefits of an invasive compared to a conservative strategy for treating UA/NSTEMI in the stent era. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (Issue 3 2005), MEDLINE and EMBASE were searched from 1996 to September 2005 with no language restrictions. SELECTION CRITERIA: Included studies were prospective trials comparing invasive with conservative strategies in UA/NSTEMI. DATA COLLECTION AND ANALYSIS: We identified 5 studies (7818 participants). Using intention-to-treat analysis with random effects models, summary estimates of relative risk (95% confidence interval [CI]) were determined for primary end-points of all-cause death, fatal and non-fatal myocardial infarction; all-cause death or non-fatal myocardial infarction; and refractory angina. Further analysis of included studies was undertaken based on whether glycoprotein IIb/IIIa receptor antagonists were used routinely. Heterogeneity was assessed using chi-square and variance (I(2)) methods. MAIN RESULTS: In the all-study analysis, mortality during initial hospitalization showed a trend to hazard with an invasive strategy; relative risk 1.59 (95% CI 0.96 to 2.64). Mortality and myocardial infarction assessed at 2-5 years in two trials were significantly decreased by an invasive strategy with relative risk of 0.75 (95% CI 0.62 to 0.92) and 0.75 (95% CI 0.61 to 0.91) respectively. The composite end-point of death or non-fatal myocardial infarction was significantly decreased by an invasive strategy at several time points after initial hospitalization. The incidence of early

A rapid extraction method for glycogen from formalin-fixed liver

Liver glycogen, a highly branched polymer, acts as our blood-glucose buffer. While past structural studies have extracted glycogen from fresh or frozen tissue using a cold-water; sucrose-gradient centrifugation technique, a method for the extraction of glycogen from formalin-fixed liver would allow the analysis of glycogen from human tissues that are routinely collected in pathology laboratories. In this study, both sucrose-gradient and formalin-fixed extraction techniques were carried out on piglet livers, with the yields, purities and size distributions (using size exclusion chromatography) compared. The formalin extraction technique, when combined with a protease treatment, resulted in higher yields (but lower purities) of glycogen with size distributions similar to the sucrose-gradient centrifugation technique. This formalin extraction procedure was also significantly faster, allowing glycogen extraction throughput to increase by an order of magnitude. Both extraction techniques were compatible with mass spectrometry proteomics, with analysis showing the two techniques were highly complementary. (C) 2014 Elsevier Ltd. All rights reserved

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Modular prevention of heart disease following acute coronary syndrome (ACS) [ISRCTN42984084]

BACKGROUND: Coronary heart disease (CHD) is a major cause of morbidity and mortality in Australia and it is recommended that all persons with unstable angina (UA) or myocardial infarction (MI) participate in secondary prevention as offered in cardiac rehabilitation (CR) programs. However, the majority of patients do not access standard CR and have higher baseline coronary risk and poorer knowledge of CHD than those persons due to commence CR. The objective of this study is to investigate whether a modular guided self-choice approach to secondary prevention improves coronary risk profile and knowledge in patients who do not access standard CR. METHODS/DESIGN: This randomised controlled trial with one year follow-up will be conducted at a tertiary referral hospital. Participants eligible for but not accessing standard CR will be randomly allocated to either a modular or conventional care group. Modular care will involve participation in individualised modules that involve choice, goal-setting and coaching. Conventional care will involve ongoing heart disease management as directed by the participant's doctors. Both modular and conventional groups will be compared with a contemporary reference group of patients attending CR. Outcomes include measured modifiable risk factors, relative heart disease risk and knowledge of risk factors. DISCUSSION: We present the rationale and design of a randomised controlled trial testing a modular approachfor the secondary prevention of coronary heart disease following acute coronary syndrome

Thinking styles and doctors' knowledge and behaviours relating to acute coronary syndromes guidelines

Background How humans think and make decisions is important in understanding behaviour. Hence an understanding of cognitive processes among physicians may inform our understanding of behaviour in relation to evidence implementation strategies. A personality theory, Cognitive-Experiential Self Theory (CEST) proposes a relationship between different ways of thinking and behaviour, and articulates pathways for behaviour change. However prior to the empirical testing of interventions based on CEST, it is first necessary to demonstrate its suitability among a sample of healthcare workers. Objectives To investigate the relationship between thinking styles and the knowledge and clinical practices of doctors directly involved in the management of acute coronary syndromes. Methods Self-reported doctors' thinking styles (N = 74) were correlated with results from a survey investigating knowledge, attitudes, and clinical practice, and evaluated against recently published acute coronary syndrome clinical guidelines. Results Guideline-discordant practice was associated with an experiential style of thinking. Conversely, guideline-concordant practice was associated with a higher preference for a rational style of reasoning. Conclusion Findings support that while guidelines might be necessary to communicate evidence, other strategies may be necessary to target discordant behaviours. Further research designed to examine the relationships found in the current study is required

Development and testing of innovative patient resources for the management of coronary heart disease (CHD): a descriptive study

BACKGROUND: Although heart disease is a major cause of morbidity and mortality the majority of patients do not access existing rehabilitation programs and patient resources are not designed to facilitate patient choice and decision-making. The objective of this study was to develop and test a series of risk factor modules and corresponding patient information leaflets for secondary prevention of CHD. METHODS: In phase one, a series of risk factor modules and management options were developed following analysis of literature and interviews with health professionals. In phase two, module information leaflets were developed using published guidelines and interviews of people with CHD. In phase three, the leaflets were tested for quality (DISCERN), readability (Flesch) and suitability (SAM) and were compared to the existing cardiac rehabilitation (CR) information leaflet. Finally, the patients assessed the leaflets for content and relevance. RESULTS: Four key risk factors identified were cholesterol, blood pressure, smoking and physical inactivity. Choice management options were selected for each risk factor and included medical consultation, intensive health professional led program, home program and self direction. Patient information needs were then identified and leaflets were developed. DISCERN quality scores were high for cholesterol (62/80), blood pressure (59/80), smoking (62/80) and physical activity (62/80), all scoring 4/5 for overall rating. The mean Flesch readability score was 75, representing "fairly easy to read", all leaflets scored in the superior category for suitability and were reported to be easy to understand, useful and motivating by persons with CHD risk factors. The developed leaflets scored higher on each assessment than the existing CR leaflets. CONCLUSION: Using a progressive three phase approach, a series of risk factor modules and information leaflets were successfully developed and tested. The leaflets will contribute to shared-decision making and empowerment for persons with CHD

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Closing the Loop: Modelling of Heart Failure Progression from Health to End-Stage Using a Meta-Analysis of Left Ventricular Pressure-Volume Loops

Introduction The American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for the classification of heart failure (HF) are descriptive but lack precise and objective measures which would assist in categorising such patients. Our aim was two fold, firstly to demonstrate quantitatively the progression of HF through each stage using a meta-analysis of existing left ventricular (LV) pressure-volume (PV) loop data and secondly use the LV PV loop data to create stage specific HF models. Methods and Results A literature search yielded 31 papers with PV data, representing over 200 patients in different stages of HF. The raw pressure and volume data were extracted from the papers using a digitising software package and the means were calculated. The data demonstrated that, as HF progressed, stroke volume (SV), ejection fraction (EF%) decreased while LV volumes increased. A 2-element lumped parameter model was employed to model the mean loops and the error was calculated between the loops, demonstrating close fit between the loops. The only parameter that was consistently and statistically different across all the stages was the elastance (Emax). Conclusions For the first time, the authors have created a visual and quantitative representation of the AHA/ACC stages of LVSD-HF, from normal to end-stage. The study demonstrates that robust, load-independent and reproducible parameters, such as elastance, can be used to categorise and model HF, complementing the existing classification. The modelled PV loops establish previously unknown physiological parameters for each AHA/ACC stage of LVSD-HF, such as LV elastance and highlight that it this parameter alone, in lumped parameter models, that determines the severity of HF. Such information will enable cardiovascular modellers with an interest in HF, to create more accurate models of the heart as it fails