Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought ...to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality.
Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment hazard ratio = 0.62 (0.45-0.86); P = 0.004 with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients 0.62 (0.45-0.85); P = 0.004 but not older (≥75 years) patients 0.98 (0.75-1.27); P = 0.96. Hospitalization due to heart failure 0.80 (0.67-0.94); P = 0.009 or cardiovascular disease 0.82 (0.67-0.99); P = 0.048 was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF.
Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.
Abstract
In recent years, the CJEU has impressively brought to bear the protection of the fundamental rights to privacy and protection of personal data as contained in the CFREU. The Court’s ...decisions in the
Digital Rights, Schrems, Tele2
, and
PNR
cases have reshaped the political and legal landscape in Europe and beyond. By restricting the powers of the governments of EU Member States and annulling legislative acts enacted by the EU legislator, the decisions had, and continue to have, effects well beyond the respective individual cases. Despite their strong impact on privacy and data protection across Europe, however, these landmark decisions reveal a number of flaws and inconsistencies in the conceptualization of the rights to privacy and protection of personal data as endorsed and interpreted by the CJEU. This Article identifies and discusses some of the shortcomings revealed in the recent CJEU privacy and data protection landmark decisions and proposes to the CJEU a strategy aimed at resolving these shortcomings going forward.
. Burkard T, Kaiser CA, Brunner‐La Rocca H, Osswald S, Pfisterer ME, Jeger RV for the BASKET Investigators (Cardiology, University Hospital; and Cardiology, Maastricht University Hospital Center, ...Maastricht, the Netherlands). Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial. J Intern Med 2012; 271: 257–263.
Objective. To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI).
Design. In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months.
Results. Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti‐inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07–3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05–3.37) were the only independent risk factors for MI.
Conclusion. In a real‐world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug–drug interaction.
Since previous randomised treatment trials in coronary disease have focused on patients younger than 75 years of age, their findings might not apply to the elderly population in whom the cardiac risk ...profile, risk of intervention, and comorbidities are increased. We aimed to assess quality of life and outcome of elderly patients with coronary disease after medical or revascularisation therapy.
In this randomised, prospective, multicentre trial, we enrolled patients aged 75 years or older with chronic angina of at least Canadian Cardiac Society class II despite at least two antianginal drugs. Patients were randomly assigned coronary angiography and revascularisation or optimised medical therapy. The primary endpoint was quality of life after 6 months, as assessed by questionnaire and the presence of major adverse cardiac events (death, non-fatal myocardial infarction, or hospital admission for acute coronary syndrome with or without the need for revascularisation). Analysis was by intention to treat.
150 patients were assigned medical therapy and 155 invasive therapy. Two protocol violators in each group were not included in the analysis. After 6 months, angina severity decreased and measures of quality of life increased in both treatment groups; however, these improvements were significantly greater after revascularisation. Major adverse cardiac events occurred in 72 (49%) of patients in the medical group and 29 (19%) in the invasive group (p < 0·0001).
Patients aged 75 years or older with angina despite standard drug therapy benefit more from revascularisation than from optimised medical therapy in terms of symptom relief and quality of life. Therefore, these patients should be offered invasive assessment despite their high risk profile followed by revascularisation if feasible.
Aim It is unknown which patients benefit most from drug-eluting stents (DES) against bare-metal stents (BMS) in a long-term clinical outcome.
Methods and results To address this question, data from ...826 consecutive patients with angioplasty, randomized 2:1 to DES vs. BMS, with an 18-month follow-up for cardiac death/myocardial infarction (MI) and non-MI-related target-vessel revascularization (TVR) were analysed for interactions between stent type and patient/vessel characteristics predicting events. Rates of 18-month TVRs were lower with DES vs. BMS use (7.5 vs. 11.6%, P = 0.05), but similar for both stents regarding cardiac death/MI (DES, 8.4%; BMS, 7.5%; P = 0.70). Significant interactions between stent type and two multivariable event predictors were identified: small stents (<3.0 mm) and bypass graft stenting. In these patient groups together (n = 268, 32%), DES reduced non-MI-related TVR (HR = 0.44; P = 0.02) and cardiac death/MI (HR = 0.44; P = 0.04), whereas in the other 558 patients (68%) TVR rate was similar (HR = 0.75; P = 0.38) and cardiac death/MI rate increased after DES (HR = 2.07; P = 0.05).
Conclusion Patients with angioplasty of small vessels or bypass grafts seem to benefit from DES use, in long-term outcome, in contrast to patients with large native vessel stenting where there might even be late harm. Still, this hypothesis needs to be tested prospectively.
We present an automated droplet reactor platform possessing parallel reactor channels and a scheduling algorithm that orchestrates all of the parallel hardware operations and ensures droplet ...integrity as well as overall efficiency. We design and incorporate all of the necessary hardware and software to enable the platform to be used to study both thermal and photochemical reactions. We incorporate a Bayesian optimization algorithm into the control software to enable reaction optimization over both categorical and continuous variables. We demonstrate the capabilities of both the preliminary single-channel and parallelized versions of the platform using a series of model thermal and photochemical reactions. We conduct a series of reaction optimization campaigns and demonstrate rapid acquisition of the data necessary to determine reaction kinetics. The platform is flexible in terms of use case: it can be used either to investigate reaction kinetics or to perform reaction optimization over a wide range of chemical domains.
This study develops an automated droplet-based reaction screening platform consisting of ten independent parallel reactor channels. Closed-loop reaction optimizations and a kinetics investigation demonstrate the platform's capabilities.
Objectives: To quantify the prognostic impact of coronary artery disease (CAD) on patients with acute heart failure (HF). Design: Prospective cohort study of 217 consecutive patients presenting with ...acute HF to the emergency department. Treatment, hospitalisation, the use of revascularisation procedures, and survival were observed during follow up of up to three years. Results: CAD was present in 153 patients (71%). Patients with and without CAD were similar with respect to age and sex. Although adequate HF treatment was initiated more rapidly among patients with CAD, their initial outcomes including hospitalisation rate, time to discharge, and total treatment cost were significantly worse. Moreover, despite higher use of angiotensin converting enzyme inhibitors and β blockers during follow up, patients with CAD had a significantly lower survival rate. Cumulative survival at 720 days was 48.7% of patients with CAD as compared with 76.4% of patients without CAD (p = 0.0004). In Cox regression analysis the presence of CAD increased the risk of death by more than 250% (hazard ratio 2.57, 95% confidence interval 1.50 to 4.39, p = 0.001). This strong association persisted after multivariate adjustments. The use of coronary angiography and coronary revascularisation procedures was low, both at initial presentation and during follow up. Conclusion: CAD is a strong and independent predictor of mortality among patients with acute HF. Whether, for example, less restrictive use of revascularisation procedures in this elderly HF population can improve the outcome for patients with CAD warrants further study.
Aims
The aim of this study was to evaluate whether biomarkers reflecting pathophysiological pathways are different between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) ...and whether the prognostic value of biomarkers is different in HFpEF vs. HFrEF.
Methods and results
A total of 458 HFrEF (LVEF ≤40%) and 112 HFpEF (LVEF ≥50%) patients aged ≥60 years with NYHA class ≥II from TIME‐CHF were included. Endpoints are 18‐month overall and HF hospitalization‐free survival. After correction for baseline characteristics that differed between the HF types, i.e. age, gender, body mass index, systolic blood pressure, cause of HF, and AF, HFpEF patients exhibited higher soluble interleukin 1 receptor‐like 1 ST2; 37.6 (28.5–54.7) vs. 35.7 (25.6–52.2), P = 0.02, high sensitivity C‐reactive protein (hsCRP; 8.54 (3.39–25.86) vs. 6.66 (2.42–15.39), P = 0.01), and cystatin‐C 1.94 (1.57–2.37) vs. 1.75 (1.39–2.12), P = 0.01. In contrast, HFrEF patients exhibited higher NT‐proBNP 2142 (1473–4294) vs. 4202 (2239–7411), P < 0.001, high sensitivity troponin T hsTnT; 27.7 (16.8–48.0) vs. 32.4 (19.2–59.0), P = 0.03, and haemoglobin 124 (110–135) vs. 134 (122–145), P < 0.001. In addition to these clinical characteristics, NT‐proBNP, haemoglobin, cystatin‐C, hsTnT, and ST2 improved the area under the curve from 0.86 (0.82–0.89) to 0.91 (0.87–0.94; P < 0.001) for discriminating HFpEF from HFrEF. There were no significant interactions between HFpEF and HFrEF when considering the prognostic value of the investigated biomarkers (P > 0.10 for both endpoints), except for cystatin‐C which had less prognostic impact in HFpEF (P < 0.01).
Conclusion
Biomarker levels suggest a different amount of activation of several pathophysiological pathways between HFpEF and HFrEF. No important differences in the prognostic value of biomarkers in HFpEF vs. HFrEF were found except for cystatin‐C, and for NT‐proBNP in the NT‐proBNP‐guided study arm only, both of which had less prognostic value in HFpEF.
Trial registration
ISRCTN43596477
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