In this pre-specified subanalysis of the SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) trial, which examined the effects of ...nebivolol in elderly heart failure (HF) patients, we explored the effects of left ventricular ejection fraction (EF) on outcomes, including the subgroups impaired EF (< or =35%) and preserved EF (>35%).
Beta-blockers are established drugs in patients with HF and impaired EF, but their value in preserved EF is unclear.
We studied 2,111 patients; 1,359 (64%) had impaired (< or =35%) EF (mean 28.7%) and 752 (36%) had preserved (>35%) EF (mean 49.2%). The effect of nebivolol was investigated in these 2 groups, and it was compared to explore the interaction of EF with outcome. Follow-up was 21 months; the primary end point was all-cause mortality or cardiovascular hospitalizations.
Patients with preserved EF were more often women (49.9% vs. 29.8%) and had less advanced HF, more hypertension, and fewer prior myocardial infarctions (all p < 0.001). During follow-up, the primary end point occurred in 465 patients (34.2%) with impaired EF and in 235 patients (31.2%) with preserved EF. The effect of nebivolol on the primary end point (hazard ratio HR of nebivolol vs. placebo) was 0.86 (95% confidence interval: 0.72 to 1.04) in patients with impaired EF and 0.81 (95% confidence interval: 0.63 to 1.04) in preserved EF (p = 0.720 for subgroup interaction). Effects on all secondary end points were similar between groups (HR for all-cause mortality 0.84 and 0.91, respectively), and no p value for interaction was <0.48.
The effect of beta-blockade with nebivolol in elderly patients with HF in this study was similar in those with preserved and impaired EF.
To study the prevalence and medium term outcome of subclinical rheumatic heart disease (RHD) in India.
Cross sectional echocardiographic screening study.
School children aged 5-15 years living in ...rural areas of north India.
A cross sectional echocardiographic screening study was carried out among 6270 randomly selected school children aged 5-15 years (10.8 ± 2.6 years; 52.7% male). Of all the abnormal cases, 100 children (78%) were restudied at a mean follow-up of 15.4 ± 6.6 months.
Echocardiographic screening.
Echocardiography-Doppler criteria based prevalence of RHD.
Clinical examination detected mitral regurgitation in five patients and the estimated prevalence of clinical RHD was 0.8/1000 school children. Echocardiography-Doppler diagnosed RHD in 128 cases, giving a prevalence of 20.4/1000 school children (95% CI 16.9 to 23.9/1000 children). On multivariate analysis, older age (OR 1.93, 95% CI 1.29 to 2.88; p = 0.001), female sex (OR 1.84, 95% CI 1.25 to 2.72; p = 0.002) and government funded school student, which is a surrogate measure of lower socioeconomic status (OR 1.55, 95% CI 1.02 to 2.34; p = 0.039) were found to be independent predictors of RHD. On follow up, the severity of subclinical RHD was non-progressive in 68 children (68%) while it worsened in four (4%) and regressed in 28 children (28%).
The prevalence of RHD is several fold higher using echocardiographic screening compared with clinical examination. The prevalence is higher among girls and children of lower socioeconomic status. In the majority of cases, subclinical RHD appears to be non-progressive on medium term follow up. Routine echocardiographic screening may be indicated in populations at high risk of RHD.
Background Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed ...erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure. Methods An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613). Results Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2-188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0-121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (−0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (−226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure–related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37-0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34-0.99, P = .047) was observed, although the number of events was limited. Conclusion Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.
Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous ...markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use.
Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography. Clinicians were blinded to all risk assessments, consisting of conventional factors, radial artery pulse wave analysis, 5-minute heart rate variability, high-sensitivity C-reactive protein and B-type natriuretic peptide (BNP). Blinded, independent adjudication was performed for all-cause mortality and the composite of death, myocardial infarction or stroke, analysed with Cox proportional hazards regression.
Five hundred twenty-two patients were assessed with median age 66 years and 21% prior revascularization. Median baseline left ventricular ejection fraction was 64%, and 62% had ≥ 50% stenosis on angiography. During 5.0 years median follow-up, 30% underwent percutaneous and 16% surgical revascularization. In multivariate analysis, only age and BNP were independently associated with outcomes. The adjusted hazard ratio per log unit increase in BNP was 2.15 for mortality (95% CI 1.45-3.19; p = 0.0001) and 1.27 for composite events (1.04-1.54; p = 0.018). Patients with baseline BNP > 100 pg/mL had substantially higher mortality and composite events (20.9% and 32.2%) than those with BNP ≤ 100 pg/mL (5.6% and 15.5%). BNP improved both classification and discrimination of outcomes (p ≤ 0.003), regardless of left ventricular systolic function. Conversely, high-sensitivity C-reactive protein, pulse wave analysis and heart rate variability were unrelated to prognosis at 5 years after risk modification and treatment of coronary disease.
Conventional risk factors and other markers of arterial compliance, inflammation and autonomic function have limited value for prediction of outcomes in risk-modified patients assessed for coronary disease. BNP can independently identify patients with subtle impairment of cardiac function that might benefit from more intensive management.
Clinicaltrials.gov, NCT00403351 Registered on 22 November 2006.
Aims The PREDICT Study is a prospective cohort study designed to evaluate coronary artery calcification score (CACS) as a predictor of cardiovascular events in type 2 diabetes (T2DM). Methods and ...results A total of 589 patients with no history of cardiovascular disease and with established T2DM had CACS measured, as well as risk factors, including plasma lipoprotein, apolipoprotein, homocysteine and C-reactive protein concentrations, homeostasis model assessment insulin resistance (HOMA-IR), and urine albumin creatinine ratio. Participants were followed for a median of 4 years and first coronary heart disease (CHD) and stroke events were identified as primary endpoints. There were 66 first cardiovascular events (including 10 strokes). CACS was a highly significant, independent predictor of events (P < 0.001), with a doubling in CACS being associated with a 32% increase in risk of events (29% after adjustment). Hazard ratios relative to CACS in the range 0–10 Agatston units (AU) were: CACS 11–100 AU, 5.4 (P = 0.02); 101–400 AU 10.5 (P = 0.001); 401–1000 AU, 11.9 (P = 0.001), and >1000 AU, 19.8 (P < 0.001). Only HOMA-IR predicted primary endpoints independently of CACS (P = 0.01). The areas under the receiver operator characteristic curve for United Kingdom Prospective Diabetes Study (UKPDS) risk engine primary endpoint risk and for UKPDS risk plus CACS were 0.63 and 0.73, respectively (P = 0.03). Conclusion Measurement of CACS is a powerful predictor of cardiovascular events in asymptomatic patients with T2DM and can further enhance prediction provided by established risk models.
Objective To develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infarction to facilitate triage and management of patients with ...acute coronary syndrome. Design Prospective multinational observational study in which we used multivariable regression to develop a final predictive model, with prospective and external validation. Setting Ninety four hospitals in 14 countries in Europe, North and South America, Australia, and New Zealand. Population 43 810 patients (21 688 in derivation set; 22 122 in validation set) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events (GRACE) study between April 1999 and September 2005. Main outcome measures Death and myocardial infarction. Results 1989 patients died in hospital, 1466 died between discharge and six month follow-up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors independently predicted death and the combined end point of death or myocardial infarction in the period from admission to six months after discharge: age, development (or history) of heart failure, peripheral vascular disease, systolic blood pressure, Killip class, initial serum creatinine concentration, elevated initial cardiac markers, cardiac arrest on admission, and ST segment deviation. The simplified model was robust, with prospectively validated C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infarction from admission to six months after discharge. The external applicability of the model was validated in the dataset from GUSTO IIb (global use of strategies to open occluded coronary arteries). Conclusions This risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infarction. It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome.
Atopaxar (E5555) is a reversible protease-activated receptor-1 thrombin receptor antagonist that interferes with platelet signaling. The primary objective of the Lessons From Antagonizing the ...Cellular Effects of Thrombin-Acute Coronary Syndromes (LANCELOT—ACS) trial was to evaluate the safety and tolerability of atopaxar in patients with ACS.
Six hundred and three subjects were randomized within 72 hours of non-ST-elevation ACS to 1 of 3 doses of atopaxar (400-mg loading dose followed by 50, 100, or 200 mg daily) or matching placebo. The incidence of Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) major or minor bleeding did not differ significantly between the combined atopaxar and placebo groups (3.08% versus 2.17%, respectively; P=0.63), and there was no dose-related trend (P=0.80). The incidence of CURE major bleeding was numerically higher in the atopaxar group compared with the placebo group (1.8% versus 0%; P=0.12). The incidence of cardiovascular death, myocardial infarction, stroke, or recurrent ischemia was similar between the atopaxar and placebo arms (8.03% versus 7.75%; P=0.93). The incidence of CV death, MI, or stroke was 5.63% in the placebo group and 3.25% in the combined atopaxar group (P=0.20). Dose-dependent trends for efficacy were not seen. Atopaxar significantly reduced ischemia on continuous ECG monitoring (Holter) at 48 hours compared with placebo (relative risk, 0.67; P=0.02). Transient dose-dependent transaminase elevation and relative QTc prolongation were observed with the highest doses of atopaxar.
In patients after ACS, atopaxar significantly reduced early ischemia on Holter monitoring without a significant increase in major or minor bleeding. Larger trials are required to fully establish the efficacy and safety of atopaxar.
URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00548587.
We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients ...with left-ventricular dysfunction or heart failure.
Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method.
Overall 12 763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5966), mortality was lower with ACE inhibitors than with placebo (702/2995 23·4% vs 866/2971 29·1%; odds ratio 0·74 95% Cl 0·66–0·83), as were the rates of readmission for heart failure (355 11·9% vs 460 15·5%; 0·73 0·63–0·85), reinfarction (324 10·8% vs 391 13·2%; 0·80 0·69-0·94), or the composite of these events (1049 35·0% vs 1244 41·9%; 0·75 0·67–0·83; all p < 0·001). For all five trials the ACE-inhibitor group had lower rates of death than the placebo group (1467/6391 23·0% vs 1710/6372 26·8%; 0·80 0·74–0·87) and lower rates of reinfarction (571 8·9% vs 703 11·0%; 0·79 0·70–0·89), readmission for heart failure (876 13-·% vs 1202 18·9%; 0·67 0·61–0·74), and the composite of these events (2161 33·8% vs 2610 41·0%; 0·72 0·67–0·78; all p < 0·0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and β-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.
This systematic overview shows that ACE inhibitors lower rates of mortality, myocardial infarction, and hospital admission for heart failure in patients with left-ventricular dysfunction or heart failure with or without a recent myocardial infarct. The use of ACE inhibitors should be part of routine practice in these patients.
Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of ...life-saving therapy.
This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR).
Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm.
Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval CI: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR.
Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.
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Accurate estimation of risk for untoward outcomes after patients have been hospitalized for an acute coronary syndrome (ACS) may help clinicians guide the type and intensity of therapy.
To develop a ...simple decision tool for bedside risk estimation of 6-month mortality in patients surviving admission for an ACS.
A multinational registry, involving 94 hospitals in 14 countries, that used data from the Global Registry of Acute Coronary Events (GRACE) to develop and validate a multivariable stepwise regression model for death during 6 months postdischarge. From 17,142 patients presenting with an ACS from April 1, 1999, to March 31, 2002, and discharged alive, 15,007 (87.5%) had complete 6-month follow-up and represented the development cohort for a model that was subsequently tested on a validation cohort of 7638 patients admitted from April 1, 2002, to December 31, 2003.
All-cause mortality during 6 months postdischarge after admission for an ACS.
The 6-month mortality rates were similar in the development (n = 717; 4.8%) and validation cohorts (n = 331; 4.7%). The risk-prediction tool for all forms of ACS identified 9 variables predictive of 6-month mortality: older age, history of myocardial infarction, history of heart failure, increased pulse rate at presentation, lower systolic blood pressure at presentation, elevated initial serum creatinine level, elevated initial serum cardiac biomarker levels, ST-segment depression on presenting electrocardiogram, and not having a percutaneous coronary intervention performed in hospital. The c statistics for the development and validation cohorts were 0.81 and 0.75, respectively.
The GRACE 6-month postdischarge prediction model is a simple, robust tool for predicting mortality in patients with ACS. Clinicians may find it simple to use and applicable to clinical practice.
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