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Aims Renal failure is a major challenge in treating heart failure ( HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function ( WRF) and the relationship to outcome. Methods and results This post-hoc analysis of TIME-CHF ( NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit ( n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/ dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system ( RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses ( P = 0.0002) and more spironolactone ( P = 0.02), whereas beta-blockers ( P = 0.69) did not differ and lower doses of RAS-blockers were given ( P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given ( P = 0.001), but not with low doses ( P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients ( P <0.001), but most in those with WRF III ( P <0.05 for interaction). RAS-blockade was associated with improved outcome ( P = 0.006), irrespective of WRF III. Conclusion Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Chronic kidney disease (CKD) is associated with worse outcomes in patients with coronary artery disease (CAD). How CKD influences the benefit-risk balance of drug-eluting stents (DES) versus bare-metal stents (BMS) is less known. Methods and results: In the multicentre BASKET-PROVE trial, 2314 patients in need of large coronary stenting (≥3.0mm) were randomised 2:1 to DES or BMS. In an a priori planned secondary analysis, outcomes were evaluated according to renal function defined by estimated glomerular filtration rates (eGFR; normal: eGFR≥60ml/min/1.73m2; CKD: eGFR<60ml/min/1.73m2). The primary endpoint was the first major adverse cardiac event (MACE: cardiac death, myocardial infarction, target vessel revascularisation) up to 2years. A Cox proportional-hazard model was used to evaluate adjusted relative risks (hazard rates, HRs) for BMS versus DES. The interaction of stent type and renal function was tested. CKD patients (189 (11.2%)/1681 with such data) had a 2-year MACE rate of 8.5% versus 7.4% in those without CKD [HR 0.98 (0.56–1.72), p=0.95] with cardiac mortalities of 5.3% and 1.5%, respectively (p=0.002, non-significant after baseline adjustments). The MACE rate was lower in CKD patients with DES than with BMS [4.9% versus 15.2%, p=0.017, HR 0.29(0.10–0.80)] as was the MACE rate in patients without CKD [5.6% with DES versus 11.1% with BMS, p<0.0001, HR 0.51(0.35–0.75)]. No significant interaction between stent type and renal function was found. Conclusions: This analysis of patients needing large coronary artery stenting confirms the increased mortality of CKD patients and documents a long-term benefit of DES compared to BMS irrespective of kidney function. [Copyright &y& Elsevier]

We evaluated the use and outcomes of drug-eluting stents (DESs) and bare metal stents (BMSs) in a large primary percutaneous coronary intervention (PCI) acute ST-elevation myocardial infarction (MI) trial. Recently concerns have been raised with “off-label” use of DESs for short- and long-term clinical outcomes. Limited randomized data exist evaluating DESs versus BMSs in ST-elevation MI. Patients (n = 5,745) in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial were categorized by stent type used. Baseline variables and clinical outcomes were collected at 90 days and 6 months. Outcomes by stent type were adjusted for using conventional multivariable predictors of 90-day mortality (age, anterior location, total ST-segment deviation, and Killip class), time to PCI, and Thrombolysis In Myocardial Infarction grade flow. Stents were deployed (at the investigator''s discretion) in 5,124 patients (89.2%) with acute MI, with DES use in 2,221 (43.3%) and BMS use in 2,903 (56.7%). Patients receiving DESs were younger (median 59 vs 63 years of age, p <0.001), had left anterior descending coronary artery PCI (57.9% vs 48.1%, p <0.001), and often were treated in the United States (58.2%). DES-treated patients had a lower adjusted mortality at 90 days (hazard ratio 0.73, 95% confidence interval [CI] 0.54 to 0.99, p = 0.046) and trended toward lower mortality (hazard ratio 0.77, 95% CI 0.58 to 1.03, p = 0.084) and recurrent MI (hazard ratio 0.81, 95% CI 0.59 to 1.11, p = 0.186) at 6 months compared with BMSs. In conclusion, in this observational analysis of stent use from a large primary percutaneous intervention for acute MI trial, DESs appear as safe as BMSs with similar 6-month clinical outcomes with regard to death and recurrent MI. [Copyright &y& Elsevier]

Background: Few studies describe recent changes in the incidence, treatment, and outcomes of cardiogenic shock. Objective: To examine temporal trends in the incidence, therapeutic management, and mortality rates of patients with the acute coronary syndrome (ACS) and cardiogenic shock, and to assess associations of therapeutic management with death and cardiogenic shock developing during hospitalization. Design: Analysis of registry data collected among patients admitted to hospitals between 1997 and 2006. Setting: 70 of the 106 acute cardiac care hospitals in Switzerland. Patients: 23 696 adults with ACS enrolled in the AMIS (Acute Myocardial Infarction in Switzerland) Plus Registry. Measurements: Cardiogenic shock incidence; treatment, including rates of percutaneous coronary intervention; and in-hospital mortality rates. Results: Rates of overall cardiogenic shock (8.3% of patients with ACS) and cardiogenic shock developing during hospitalization (6.0% of patients with ACS and 71.5% of patients with cardiogenic shock) decreased during the past decade (P < 0.001 for temporal trend), whereas rates of cardiogenic shock on admission remained constant (2.3% of patients with ACS and 28.5% of patients with cardiogenic shock). Rates of percutaneous coronary intervention increased among patients with cardiogenic shock (7.6% to 65.9%; P = 0.010), whereas in-hospital mortality decreased (62.8% to 47.7%; P = 0.010). Percutaneous coronary intervention was independently associated with lower risk for both in-hospital mortality in all patients with ACS (odds ratio, 0.47 [95% CI, 0.30 to 0.73]; P = 0.001) and cardiogenic shock development during hospitalization in patients with ACS but without cardiogenic shock on admission (odds ratio, 0.59 [CI, 0.39 to 0.89]; P = 0.012). Limitations: There was no central review of cardiogenic shock diagnoses, and follow-up duration was confined to the hospital stay. Unmeasured or inaccurately measured characteristics may have confounded observed associations of treatment with outcomes. Conclusion: Over the past decade, rates of cardiogenic shock developing during hospitalization and in-hospital mortality decreased among patients with ACS. Increased percutaneous coronary intervention rates were associated with decreased mortality among patients with cardiogenic shock and with decreased development of cardiogenic shock during hospitalization. [ABSTRACT FROM AUTHOR]

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels forthe US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial.comparisons between stents with indirect evidence from othertrials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes. [ABSTRACT FROM AUTHOR]

This article presents a clinical trial on the effects of percutaneous coronary interventions (PCI) in silent ischemia after myocardial infarction (MI). The objective of the study was to determine if PCI, compared with drug therapy, improves long-term outcome of asymptomatic patients with silent ischemia after an MI. The conclusion of the trial was that among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1-or 2-vessel coronary arteries disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.

Replies to reader comment on research by the author about the outcome of medical and invasive therapy for aged patients with angina. Idea that the issue was quality of life and not mortality in the TIME study.

Aims Evaluation of predictors of silent coronary artery disease (SCAD) in high-risk asymptomatic diabetic patients and to evaluate their two-year outcome. Methods and results Four hundred diabetic patients without prior CAD but at high CAD risk underwent myocardial perfusion scintigraphy (MPS) in this prospective multicentre outcome trial. MPS were abnormal in 22% of patients. Male sex (OR 2.223, 1.152–4.290; p = 0.017), diabetes duration (OR 1.049,1.015–1.085; p = 0·005), peripheral artery disease (OR 2.134, 1·150–3.961; p = 0.016), smoking (OR 2.064, 1.109–3.839; p = 0·022), systolic blood pressure (OR 1.014, 1.00–1.03, p = 0·056), brain natriuretic peptide (OR 1.002, 1.001–1.004, p = 0·005) independently predicted an abnormal MPS: if < 2 and > 3 predictors were present, 3.2% and 47% patients had an abnormal MPS, respectively (p < 0·001). Two-year major adverse cardiac event rates increased from 2·9% to 14·6%, cardiac death rates from 0·6% to 4·1% in patients with summed stress scores ≤ 10 and > 10%, respectively (each p < 0.045). Conclusions Male sex, diabetes duration, peripheral artery disease, smoking, elevated systolic blood pressure and increased brain-natriuretic peptides independently predicted SCAD. In presence of > 3 predictors, almost 50% of patients had an abnormal MPS. They may benefit from screening by MPS since the extent of the MPS abnormality discriminated clearly between a favourable compared to a bad 2-year outcome. However, even highest risk patients without objective evidence of CAD had a benign prognosis without need for specific evaluation or therapy. Trial Registration Number: ISRCTN87953632. [ABSTRACT FROM AUTHOR]

Background Cardiac remodeling and its reversibility are key in HF outcomes. The ST2-R2 score was recently developed to predict relevant left ventricular (LV) reverse remodeling (R2) in patients with heart failure (HF). In the present study we sought to validate the ST2-R2 score for grading improvement in LV ejection fraction (EF) and LV size at one year, and to evaluate its prognostic implication up to 4 years. Methods A total of 569 patients with baseline LVEF < 40% from three international cohorts (Barcelona, TIME-CHF, and PROTECT) were included in the study. Patients were classified into four strata based on their ST2-R2 score, which took into account concentrations of the biomarker ST2, non-ischemic etiology, absence of left bundle branch block, HF duration, baseline LVEF, and β-blocker treatment. Results A significant relationship was observed between ST2-R2 scores and changes in LVEF and indexed LV sizes. LVEF recovery (from + 5.6% to + 17.3%; p < 0.001), percentage reduction in LV end-systolic volume index (from − 6.1% to − 32.1%; p < 0.001) and in LV end-systolic diameter index (from − 1.1% to − 18.6%; p < 0.001) increased over the ST2-R2 strata. A similar trend was observed with diastolic parameters. Improvement in LV function and size was inversely predictive of mortality. Hazard ratios for risk of death, using the lower ST2-R2 score strata (< 9) as a reference, were 0.49 (p < 0.001; score 9–11), 0.27 (p < 0.001; score 12–14), and 0.17 (p < 0.001; score 15–17). Conclusions The ST2-R2 score predicts reverse LV remodeling in HF patients and is useful for predicting mortality up to 4 years. [ABSTRACT FROM AUTHOR]

Abstract: Background: The incidence of coronary artery disease (CAD) in totally asymptomatic patients with myocardial ischemia during stress testing is unknown. Methods: 54 patients with asymptomatic myocardial ischemia participated in the Swiss Interventional Study on Silent Ischemia type I (SWISSI I). Asymptomatic myocardial ischemia was verified by bicycle ergometry and stress imaging (echocardiography or scintigraphy). Findings from coronary angiographies in the course of the study constituted the main outcome. Results: Of the 54 study participants, 29 patients (53.7%) underwent coronary angiography. CAD was found in 27 of 29 patients (93.1%). In those 27 patients with CAD, 9 patients (33.3%) suffered from single vessel disease, 9 patients (33.3%) from two vessel disease, and 9 patients (33.3%) from triple vessel disease. Two patients showed left main coronary artery stenosis. Conclusion: This study shows a high incidence of relevant CAD among totally asymptomatic patients with myocardial ischemia during stress testing. Previously healthy subjects with exercise-induced ST-segment depression at check-up examinations, even if asymptomatic, should have further diagnostic evaluation. [Copyright &y& Elsevier]

This article presents the results of an 18 month study on the cost-effectiveness of drug-eluting stents in patients at high or low risk of major cardiac events. To assess the value of these medical devices, the authors looked at cost of the procedure and the rate of follow-up events which were usually vessel revascularisations avoided by placement of the stents. The study found that overall costs were higher for patients with drug-eluting stents over those with bare metal stents due to the higher price of the drug-eluting stent. If used in all patients, the drug-eluting stents would not be good value for the money. They are cost effective in patients who need small vessel or bypass graft stenting but not in those who need larger vessel stenting.

This article presents a meta-analysis of outcomes associated with drug-eluting and bare-metal stents. The study sought to see if there was a difference in outcomes between the sirolimus-eluting stents, the paclitaxel-eluting stents and the bare-metal stents. The study found that mortality was similar in all three groups. In comparing sirolimus-eluting stents with bare-metal, the drug-eluting stents were associated with the lowest rate of myocardial infarction. The risk of late definite stent thrombosis was increased with the paclitaxel-eluting stents. The reduction in target lesion revascularisation was more pronounced with the sirolimus-eluting stents which leads the authors to conclude that sirolimus-eluting stents seem to be clinically better than the other two.