Use and outcomes of dual antiplatelet therapy for acute coronary syndrome in patients with chronic kidney disease: insights from the Canadian Observational Antiplatelet Study (COAPT).

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in randomized controlled trials. We examined the practice patterns of DAPT prescription stratified by the presence of CKD. The multicentre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with ACS between December 2011 and May 2013. The present study is a subgroup analysis comparing type and duration of DAPT and associated outcomes among patients with and without CKD (eGFR < 60 ml/min/1.73 m2, calculated by CKD-EPI). Patients with CKD (275/1921, 14.3%) were prescribed prasugrel/ticagrelor less (18.5% vs 25.8%, p = 0.01) and had a shorter duration of DAPT therapy versus patients without CKD (median 382 vs 402 days, p = 0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12 months (p < 0.001) but not bleeding when compared to patients without CKD. CKD was associated with MACE in both patients on prasugrel/ticagrelor (p = 0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity = 0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p = 0.007), but not among those receiving clopidogrel (p = 0.64) (p for heterogeneity = 0.036). Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk evaluation, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

Self-Reported Sleep Duration and Quality and Cardiovascular Disease and Mortality: A Dose-Response Meta-Analysis.

Background There is growing evidence that sleep duration and quality may be associated with cardiovascular harm and mortality. Methods and Results We conducted a systematic review, meta-analysis, and spline analysis of prospective cohort studies that evaluate the association between sleep duration and quality and cardiovascular outcomes. We searched MEDLINE and EMBASE for these studies and extracted data from identified studies. We utilized linear and nonlinear dose-response meta-analysis models and used DerSimonian-Laird random-effects meta-analysis models of risk ratios, with inverse variance weighting, and the I2 statistic to quantify heterogeneity. Seventy-four studies including 3 340 684 participants with 242 240 deaths among 2 564 029 participants who reported death events were reviewed. Findings were broadly similar across both linear and nonlinear dose-response models in 30 studies with >1 000 000 participants, and we report results from the linear model. Self-reported duration of sleep >8 hours was associated with a moderate increased risk of all-cause mortality, with risk ratio , 1.14 (1.05-1.25) for 9 hours, risk ratio, 1.30 (1.19-1.42) for 10 hours, and risk ratio, 1.47 (1.33-1.64) for 11 hours. No significant difference was identified for periods of self-reported sleep <7 hours, whereas similar patterns were observed for stroke and cardiovascular disease mortality. Subjective poor sleep quality was associated with coronary heart disease (risk ratio , 1.44; 95% confidence interval, 1.09-1.90), but no difference in mortality and other outcomes. Conclusions Divergence from the recommended 7 to 8 hours of sleep is associated with a higher risk of mortality and cardiovascular events. Longer duration of sleep may be more associated with adverse outcomes compared with shorter sleep durations.

Pharmacodynamic Effects of a 6-Hour Regimen of Enoxaparin in Patients Undergoing Primary Percutaneous Coronary Intervention (PENNY PCI Study).

Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2-3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y12 inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y12 inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y12 inhibition.

In an era of rapid STEMI reperfusion with Primary Percutaneous Coronary Intervention is there a role for adjunct therapeutic hypothermia? A structured literature review.

Mild hypothermia has been shown to improve neurological outcome and reduce mortality following out of hospital cardiac arrest. In animal models the application of hypothermia with induced coronary occlusion has demonstrated a reduction in infarct size. Consequently, hypothermia has been proposed as a treatment, in addition to Primary Percutaneous Coronary Intervention (PPCI) for ST segment elevation myocardial infarction (STEMI). However, there is incomplete understanding of the mechanism and magnitude of the protective effect of hypothermia on the myocardium, and limited outcome data. We undertook a structured literature review of therapeutic hypothermia as adjuvant to PPCI for acute STEMI. We examined the feasibility, safety, impact on infarct size and the resultant effect on major adverse cardiac events and mortality. There were 13 studies between 1946 and 2016. With the exception of one study, therapeutic hypothermia for STEMI was reported to be feasible and safe, and its only demonstrable benefit was a modest reduction in post-infarct heart failure events. Evidence to date, however, is from small clinical trials and in an era of low early mortality following PPCI for STEMI, demonstrating a mortality benefit will be challenging. Post-myocardial infarction left ventricular dysfunction is a more frequent, alternative clinical outcome and therefore any intervention that mitigates this warrants further investigation.

Association of Clinical Factors and Therapeutic Strategies With Improvements in Survival Following Non-ST-Elevation Myocardial Infarction, 2003-2013.

IMPORTANCE: International studies report a decline in mortality following non-ST-elevation myocardial infarction (NSTEMI). Whether this is due to lower baseline risk or increased utilization of guideline-indicated treatments is unknown. OBJECTIVE: To determine whether changes in characteristics of patients with NSTEMI are associated with improvements in outcomes. DESIGN, SETTING, AND PARTICIPANTS: Data on patients with NSTEMI in 247 hospitals in England and Wales were obtained from the Myocardial Ischaemia National Audit Project between January 1, 2003, and June 30, 2013 (final follow-up, December 31, 2013). EXPOSURES: Baseline demographics, clinical risk (GRACE risk score), and pharmacological and invasive coronary treatments. MAIN OUTCOMES AND MEASURES: Adjusted all-cause 180-day postdischarge mortality time trends estimated using flexible parametric survival modeling. RESULTS: Among 389 057 patients with NSTEMI (median age, 72.7 years [IQR, 61.7-81.2 years]; 63.1% men), there were 113 586 deaths (29.2%). From 2003-2004 to 2012-2013, proportions with intermediate to high GRACE risk decreased (87.2% vs 82.0%); proportions with lowest risk increased (4.2% vs 7.6%; P= .01 for trend). The prevalence of diabetes, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, chronic renal failure, previous invasive coronary strategy, and current or ex-smoking status increased (all P < .001). Unadjusted all-cause mortality rates at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio [HR], 0.968 [95% CI, 0.966-0.971]; difference in absolute mortality rate per 100 patients [AMR/100], -1.81 [95% CI, -1.95 to -1.67]). These findings were not substantially changed when adjusted additively by baseline GRACE risk score (HR, 0.975 [95% CI, 0.972-0.977]; AMR/100, -0.18 [95% CI, -0.21 to -0.16]), sex and socioeconomic status (HR, 0.975 [95% CI, 0.973-0.978]; difference in AMR/100, -0.24 [95% CI, -0.27 to -0.21]), comorbidities (HR, 0.973 [95% CI, 0.970-0.976]; difference in AMR/100, -0.44 [95% CI, -0.49 to -0.39]), and pharmacological therapies (HR, 0.972 [95% CI, 0.964-0.980]; difference in AMR/100, -0.53 [95% CI, -0.70 to -0.36]). However, the direction of association was reversed after further adjustment for use of an invasive coronary strategy (HR, 1.02 [95% CI, 1.01-1.03]; difference in AMR/100, 0.59 [95% CI, 0.33-0.86]), which was associated with a relative decrease in mortality of 46.1% (95% CI, 38.9%-52.0%). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies.

Comparison of Early Versus Delayed Oral ß Blockers in Acute Coronary Syndromes and Effect on Outcomes.

The aim of this study was to determine if earlier administration of oral ß â€‹blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous ß blockers or remained free of any ß â€‹blocker treatment during hospital stay, 23 as timing of oral ß â€‹blocker administration was unknown, and 182 patients because they died before oral ß blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral ß blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early ß â€‹blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early ß â€‹blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score-matched analyses. In conclusion, in patients with ACSs, earlier administration of oral ß â€‹blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen.

Impact of left ventricular function and transaortic gradient on outcomes from transcatheter aortic valve implantation: data from the UK TAVI Registry.

AIMS: Aortic valve surgery in the presence of reduced ejection fraction (EF) or low transaortic gradient is associated with adverse outcome. Low gradient (LG) may be associated with reduced EF, known as low EF-low gradient (LEF-LG), or "paradoxically" low with normal EF (P-LG). Our aim was to investigate the impact of EF and transaortic gradient on outcome following transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We retrospectively analysed the UK TAVI Registry from 2007 to 2011 (n=2,535 consecutive patients, mean age 81.3±7.5, logistic EuroSCORE 21.8±14). Thirty-day mortality was 7.8%, low EF (<50%) was present in 39%, low gradient (<64 mmHg) was present in 27%, LEF-LG in 15% and P-LG in 12% of patients, respectively. LEF-LG patients had the highest risk profile vs. the other groups (EuroSCORE 30±16 vs. 20±12, p<0.001). Neither EF nor gradient impacted on procedural outcome or 30-day mortality. Mortality at two years was significantly higher in LEF-LG patients (34.7%), whereas, in patients with low EF/high gradient (27.8%) or normal EF/low gradient (23%), mortality was not significantly different from that of normal EF/high gradient (23%) patients. LEF-LG independently predicted reduced survival, HR 1.7 (1.4-2.1). CONCLUSIONS: Neither low EF nor low gradient affected procedural success or 30-day mortality. Long-term survival was reduced in LEF-LG patients but not in those with low EF and high gradient or P-LG with normal EF.

Effects of dietary fibre type on blood pressure: a systematic review and meta-analysis of randomized controlled trials of healthy individuals.

OBJECTIVE: To determine the effect of different types of dietary fibre on SBP and DBP. METHODS: A systematic review of the literature and a meta-analysis of randomized controlled trials using random-effects models. Eligibility criteria for studies included randomized controlled trials of at least 6 weeks duration, testing a fibre isolate or fibre-rich diet against a control or placebo published between 1 January 1990 and 1 December 2013. RESULTS: Twenty-eight trials met the inclusion criteria and reported fibre intake and SBP and/or DBP. Eighteen trials were included in a meta-analysis. Studies were categorized into 1 of 12 fibre-type categories. The pooled estimates for all fibre types were -0.9 mmHg [95% confidence interval (CI) -2.5 to 0.6 mmHg] and -0.7 mmHg (95% CI -1.9 to 0.5 mmHg) for SBP and DBP, respectively. The median difference in total fibre was 6 g. Analyses of specific fibre types concluded that diets rich in beta-glucans reduce SBP by 2.9 mmHg (95% CI 0.9 to 4.9 mmHg) and DBP by 1.5 mmHg (95% CI 0.2 to 2.7 mmHg) for a median difference in beta-glucans of 4 g. Heterogeneity for individual fibre types was generally low. CONCLUSIONS: Higher consumption of beta-glucan fibre is associated with lower SBP and DBP. The results of this review are consistent with recommendations to increase consumption of foods rich in dietary fibre, but some additional emphasis on sources of beta-glucans, such as oats and barley, may be warranted.

Exercise-based cardiac rehabilitation in patients with heart failure: a meta-analysis of randomised controlled trials between 1999 and 2013.

BACKGROUND: Guidelines recommend exercise-based cardiac rehabilitation (EBCR) for patients with heart failure (HF). However, established research has not investigated the longer-term outcomes including mortality and hospitalisation in light of the contemporary management of HF. METHODS: This was a systematic review including a meta-analysis of EBCR on all-cause mortality, hospital admission, and standardised exercise capacity using four separate exercise tests in patients with heart failure over a minimum follow-up of six months from January 1999-January 2013. Electronic searches were performed in the databases: Medline, CENTRAL, EMBASE, CINAHL, and PsycINFO constrained to randomised controlled trials (RCTs). RESULTS: A total of 46 separate RCTs qualified for the meta-analysis, which employed conventional methods for binary and continuous data. The relative risk (RR) ratio for hospital admission (12 studies) was significantly reduced (RR ratio 0.65; 95% confidence interval (CI) 0.50-0.84; p = 0.001), but mortality (21 studies) was not (RR ratio 0.88; 95% CI 0.77-1.02; p = 0.08). The standardised exercise capacity (26 studies) showed a standardised mean difference (SMD) in favour of the exercise group as compared with the controls (SMD 0.98, 95% CI 0.59-1.37; p < 0.001). Women and elderly people were less frequently enrolled in the RCTs independent of the outcomes. Heterogeneity was moderate to high in the analysis of hospital admission and the standardised exercise capacity demonstrated through skewedness in their funnel plots. CONCLUSIONS: EBCR in patients with HF is associated with significant improvements in exercise capacity and hospital admission over a minimum of six months follow-up, but not in all-cause mortality.

Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention.

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction (NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention (PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.

Effects of angiotensin-converting enzyme inhibitors and beta blockers on clinical outcomes in patients with and without coronary artery obstructions at angiography (from a Register-Based Cohort Study on Acute Coronary Syndromes).

We sought to determine the effectiveness of angiotensin-converting enzyme (ACE) inhibition and ß-blocker treatment as a function of the degree of coronary artery disease (CAD) obstruction at angiography. The Evaluation of Methods and Management of Acute Coronary Events registry enrolled patients who had been hospitalized for an acute coronary syndrome. There were 1,602 patients who had cardiac catheterization that were used for this analysis. The main outcome measures were evidence-based therapies prescribed at discharge and 6-month incidence of all-cause mortality. The cohort consisted of 1,252 patients with obstructive CAD (>50% luminal diameter obstructed) and 350 patients with nonobstructive CAD. Multivariate logistic regression analysis adjusted for further medications and other clinical factors was performed. Patients with nonobstructive CAD had significantly (p <0.001) higher rates of ß-blocker (77.8% vs 63.3%) and lower rates of ACE-inhibitor (57.7% vs 66.4%) prescriptions. In patients with nonobstructive CAD, ACE-inhibitor therapy was clearly associated with a lower 6-month mortality (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.03 to 0.78, p = 0.004). No significant association between ß-blocker use and death was found. In patients with obstructive CAD, both ß blockers (OR 0.47, 95% CI 0.32 to 0.67, p <0.001) and ACE inhibitors (OR 0.47, 95% CI 0.26 to 0.87, p = 0.01) were significantly associated with a reduced risk of 6-month mortality. In conclusion, ACE-inhibitor therapy seems to be an effective first-line treatment for preventing the occurrence of mortality in patients with nonobstructive CAD.

Acute coronary syndrome management in older adults: guidelines, temporal changes and challenges.

Advancing age is a risk factor for the development of coronary artery disease and is an important indicator of outcome after acute coronary syndrome. As the number of older adults increases, the burden of cardiovascular disease is set to grow particularly as older adults remain disadvantaged in the delivery of acute cardiac care. This article reviews the temporal changes in the provision of guideline recommended therapies for the management of acute coronary syndrome, discusses reasons for age-dependent inequalities in care and the challenges facing clinicians.

Impact of aspirin and statins on long-term survival in patients hospitalized with acute myocardial infarction complicated by heart failure: an analysis of 1706 patients.

AIMS: Aspirin and statins are established therapies for acute myocardial infarction (MI), but their benefits in patients with chronic heart failure (HF) remain elusive. We investigated the impact of aspirin and statins on long-term survival in patients hospitalized with acute MI complicated by HF. METHODS AND RESULTS: Of 4251 patients in the Evaluation of Methods and Management of Acute Coronary Events (EMMACE)-1 and -2 observational studies, 1706 patients had HF. A propensity score-matching method estimated the average treatment effects (ATEs) of aspirin and statins on survival over 90 months. ATEs were calculated as relative risk differences in all-cause mortality comparing patients receiving aspirin and statins with controls, respectively. Moreover, combined aspirin and statins vs. none (ATE I), aspirin or statins vs. none (ATE II), and aspirin and statins vs. aspirin or statins (ATE III) were assessed. The median survival times of the ATE I, ATE II and ATE III were 25, 50, and 85 months, respectively. Regarding aspirin, the ATE was significantly improved at 6, 12, and 90 months [ATE 6 months: 10%, 95% confidence interval (CI) 3-18%], where the ATE of statins favoured survival at 1-24 months (ATE 1 month: 5%, 95% CI 0.3-10%). Mortality was lower at 1, 6, and 24 months in those who received aspirin and statins (ATE I). When the combination was compared with either treatment alone, an effect persisted between 6 and 90 months (ATE III). CONCLUSION: In patients with acute MI complicated by HF, prescription of aspirin and statins either alone or together was associated with better long-term survival.

The effect of referral for cardiac rehabilitation on survival following acute myocardial infarction: a comparison survival in two cohorts collected in 1995 and 2003.

BACKGROUND: International guidelines recommend referral for cardiac rehabilitation (CR) after acute myocardial infarction (AMI). However, the impact on long-term survival after CR referral has not been adjusted by time-variance. We compared the effects of CR referral after hospitalization for AMI in two consecutive decades. METHODS AND RESULTS: A total of 2196 and 2055 patients were recruited in the prospective observational studies of the Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) -1 and 2 in 1995 and 2003, (1995: median age 72 years, 39% women, 74% referred vs 2003: median age 71 years, 36% women, 64% referred) and followed up through September 2010. Survival functions showed CR referral to be an independent predictor for survival in 2003, but not in 1995 (hazard ratio (HR), 0.90; 95% confidence interval [CI]; 0.70 to 1.17, p = 0.44 in 1995 vs HR, 0.80; 95% CI, 0.66 to 0.96, p = 0.02 in 2003) when patients entered the model at three months after discharge and had a common exit at 90 months. Significant positive and negative predictors for CR referral were beta-blocker prescription (+), reperfusion (+) and age (-) in 1995, and reperfusion (+), revascularization (+), heart failure (HF) (+), antiplatelets (+), angiotensin-converting-enzyme inhibitor (ACE-I) (+), statins (+), diabetes (-), and the modified Global Registry of Acute Cardiac Events (GRACE) risk score (-) in 2003. CONCLUSIONS: CR referral was associated with improved survival in 2003, but not in 1995 in patients admitted with acute MI.

Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis.

OBJECTIVE: To investigate dietary fibre intake and any potential dose-response association with coronary heart disease and cardiovascular disease. DESIGN: Systematic review of available literature and dose-response meta-analysis of cohort studies using random effects models. DATA SOURCES: The Cochrane Library, Medline, Medline in-process, Embase, CAB Abstracts, ISI Web of Science, BIOSIS, and hand searching. ELIGIBILITY CRITERIA FOR STUDIES: Prospective studies reporting associations between fibre intake and coronary heart disease or cardiovascular disease, with a minimum follow-up of three years and published in English between 1 January 1990 and 6 August 2013. RESULTS: 22 cohort study publications met inclusion criteria and reported total dietary fibre intake, fibre subtypes, or fibre from food sources and primary events of cardiovascular disease or coronary heart disease. Total dietary fibre intake was inversely associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day (95% confidence intervals 0.88 to 0.94)) and coronary heart disease (0.91 (0.87 to 0.94)). There was evidence of some heterogeneity between pooled studies for cardiovascular disease (I(2)=45% (0% to 74%)) and coronary heart disease (I(2)=33% (0% to 66%)). Insoluble fibre and fibre from cereal and vegetable sources were inversely associated with risk of coronary heart disease and cardiovascular disease. Fruit fibre intake was inversely associated with risk of cardiovascular disease. CONCLUSIONS: Greater dietary fibre intake is associated with a lower risk of both cardiovascular disease and coronary heart disease. Findings are aligned with general recommendations to increase fibre intake. The differing strengths of association by fibre type or source highlight the need for a better understanding of the mode of action of fibre components.

Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology.

BACKGROUND: It is unclear whether diabetes mellitus (DM) is an adverse prognostic factor in chronic heart failure (CHF) of ischaemic and non-ischaemic aetiology managed with contemporary evidence-based care. METHODS: In total, 1091 outpatients with CHF with reduced ejection fraction were prospectively observed for a mean of 960 days. Total and cardiovascular mortality was quantified after accounting for potential confounders. RESULTS: In total, 25.7% of patients had DM; this group was more likely to have CHF of ischaemic aetiology and was more symptomatic. Patients with DM received comparable medical- and device-based therapies, except for greater doses of loop diuretic. DM was associated with approximately doubled crude and adjusted risk of total and cardiovascular mortality. The association of diabetes with these outcomes in patients with ischaemic and non-ischaemic cardiomyopathies was of similar magnitude. CONCLUSIONS: In spite of advances in the management of CHF, DM remains a major adverse prognostic feature, irrespective of ischaemic/non-ischaemic aetiology.

Evaluation of the NICE mini-GRACE risk scores for acute myocardial infarction using the Myocardial Ischaemia National Audit Project (MINAP) 2003-2009: National Institute for Cardiovascular Outcomes Research (NICOR).

OBJECTIVE: To evaluate the performance of the National Institute for Health and Clinical Excellence (NICE) mini-Global Registry of Acute Coronary Events (GRACE) (MG) and adjusted mini-GRACE (AMG) risk scores. DESIGN: Retrospective observational study. SETTING: 215 acute hospitals in England and Wales. PATIENTS: 137 084 patients discharged from hospital with a diagnosis of acute myocardial infarction (AMI) between 2003 and 2009, as recorded in the Myocardial Ischaemia National Audit Project (MINAP). MAIN OUTCOME MEASURES: Model performance indices of calibration accuracy, discriminative and explanatory performance, including net reclassification index (NRI) and integrated discrimination improvement. RESULTS: Of 495 263 index patients hospitalised with AMI, there were 53 196 ST elevation myocardial infarction and 83 888 non-ST elevation myocardial infarction (NSTEMI) (27.7%) cases with complete data for all AMG variables. For AMI, AMG calibration was better than MG calibration (Hosmer-Lemeshow goodness of fit test: p=0.33 vs p<0.05). MG and AMG predictive accuracy and discriminative ability were good (Brier score: 0.10 vs 0.09; C statistic: 0.82 and 0.84, respectively). The NRI of AMG over MG was 8.1% (p<0.05). Model performance was reduced in patients with NSTEMI, chronic heart failure, chronic renal failure and in patients aged ≥85 years. CONCLUSIONS: The AMG and MG risk scores, utilised by NICE, demonstrated good performance across a range of indices using MINAP data, but performed less well in higher risk subgroups. Although indices were better for AMG, its application may be constrained by missing predictors.

Acute coronary syndromes: an old age problem.

The increasing population in older age will lead to greater numbers of them presenting with acute coronary syndromes (ACS). This has implications on global healthcare resources and necessitates better management and selection for evidenced-based therapies. The elderly are a high risk group with more significant treatment benefits than younger ACS. Nevertheless, age related inequalities in ACS care are recognised and persist. This discrepancy in care, to some extent, is explained by the higher frequency of atypical and delayed presentations in the elderly, and less diagnostic electrocardiograms at presentation, potentiating a delay in ACS diagnosis. Under estimation of mortality risk in the elderly due to limited consideration for physiological frailty, co-morbidity, cognitive/psychological impairment and physical disability, less input by cardiology specialists and lack of randomised, controlled trials data to guide management in the elderly may further confound the inequality of care. While these inequalities exist, there remains a substantial opportunity to improve age related ACS outcomes. The selection of elderly patients for specific therapies and medication regimens are unanswered. There is a growing need for randomised, controlled trial data to be more representative of the population and enroll those of advanced age with co-morbidity. A lack of reporting of adverse events, such as renal impairment post coronary angiography, in the elderly further limit risk benefit decisions. Substantial improvements in care of elderly ACS patients are required and should be advocated. Ultimately, these improvements are likely to lead to better outcomes post ACS. However, the improvement in outcome is not infinite and will be limited by non-modifiable factors of age-related risk.

Is cardiac rehabilitation still relevant in the new millennium?

Cardiac rehabilitation is an evidence-based intervention which has evolved over time and incorporates physical, psycho-social and educational components with the aim of improving the patients' functioning following a cardiac event. The evidence base for cardiac rehabilitation following acute myocardial infarction has been growing over the past half a century. Individual randomized control trials were small and, therefore, mortality outcomes usually failed to reach significance; however, meta-analyses have proven consistently that participation in cardiac rehabilitation following a myocardial infarction is associated with a significant improvement in mortality. In the era of revascularization and improved drug therapies, observational studies still provide evidence that independent of other treatments, cardiac rehabilitation is a life-saving measure. Although early studies often only studied young males, more contemporary data include patients from all sectors of society and have found that groups such as women, the elderly and those with heart failure appear to have greater mortality benefits compared with the traditional young male cohort. Uptake remains a problem and one challenge for the future is ensuring improved uptake on to good-quality rehabilitation programmes and demonstrating these positive effects.

Multiple imputation for completion of a national clinical audit dataset.

The Myocardial Ischaemia National Audit Project (MINAP) is a register of heart attacks covering 234 acute admitting hospitals in England and Wales. It is used to assess the extent to which hospitals are attaining the government targets for patients with heart attacks (myocardial infarction). MINAP is therefore of national importance in coronary care and of potential international importance for research. As with most observational databases, there is missing data in MINAP, which has the potential to bias statistical analyses. In this paper, we use multiple imputation to reduce the impact of missing data and we give details of how our imputation scheme was implemented. The key contribution of this paper is the provision of multiply completed datasets, suited to a range of analyses, that can be used to make efficient inferences without the distractions of missing data. Our work will assist MINAP in achieving its priority goal of providing useful data with which to analyse patient care.