Natriuretic Peptide-Based Inclusion Criteria in a Heart Failure Clinical Trial: Insights From COMMANDER HF.

OBJECTIVES: This study investigated the effects of a mid-trial protocol amendment requiring elevated natriuretic peptides for inclusion in the COMMANDER-HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure) trial. BACKGROUND: Heart failure (HF) trials that select patients based on history of HF hospitalization alone are susceptible to regional variations in event rates. Elevated plasma concentrations of natriuretic peptides (NPs) as selection criteria may help HF ascertainment and risk enrichment. In the COMMANDER-HF trial, B-type natriuretic peptide ≥200 ng/l or N-terminal pro-B-type natriuretic peptide ≥800 ng/l were added to inclusion criteria as a mid-trial protocol amendment, providing a unique case-study of NP-based inclusion criteria. METHODS: We compared the baseline characteristics, event rates, and treatment effects for patients enrolled before and after the NP protocol amendment. The primary endpoint was all-cause death, myocardial infarction, or stroke. Secondary endpoints included HF rehospitalization and cardiovascular death. RESULTS: A total of 5,022 patients with left ventricular ejection fraction ≤40% and coronary artery disease were included. Compared to patients enrolled before the NP protocol amendment, those enrolled post-amendment (n = 3,867, 77%) were older, more often had diabetes, and had lower values for body mass index, left ventricular ejection fraction, and estimated glomerular filtration rate, higher heart rate, and higher event rates: primary endpoint (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.16 to 1.50), cardiovascular death (HR: 1.29; 95% CI: 1.11 to 1.50), HF rehospitalization (HR: 1.31; 95% CI: 1.15 to 1.49), and major bleeding (HR: 1.71; 95% CI: 1.11 to 2.65). Differences between pre- and post-amendment rates were confined to and driven by Eastern Europe. This protocol amendment did not modify the neutral effect of rivaroxaban on the primary endpoint (p interaction = 0.36) or secondary endpoints. CONCLUSIONS: In a global event-driven trial of rivaroxaban in HF, requiring elevated NPs for inclusion increased event rates allowing earlier completion of the trial but did not modify treatment effect. These data inform future HF trials regarding the expected impact of NP-based inclusion criteria on patient characteristics and event rates. (COMMANDER HF [A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure] NCT01877915).

[Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicines].

Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicine. The patients were divided into two groups： the simple Western medicine treatment group (control group) and the traditional Chinese medicine and Western medicine treatment group (treatment group). The patients in the two groups were treated with conventional western medicine.The treatment group was given based on Buxin Yishen decoction, a total of three courses of treatment to observe the two groups of patients before and after treatment of total efficacy, cardiac function indicators, changes in renal function indicators. The total efficacy of the treatment group and the control group were 91.80% and 72.41%, respectively. There were significant differences between the two groups (P<0.01). The cardiac function indexes and renal function indexes of the treatment group and the control group before and after treatment (P<0.01). Compared with the two groups, the left ventricular function, Hematuria natriuretic peptide, serum creatinine, urea nitrogen, cystatin-C were improved, and the treatment group (P<0.05~0.01). The results showed that the combination of traditional Chinese and Western medicine treatment can improve the clinical efficacy of type 2 heart and kidney syndrome, significantly improve heart and kidney function, better than conventional Western medicine treatment, and has good safety.

A new model for integrated heart failure and palliative advanced homecare--rationale and design of a prospective randomized study.

BACKGROUND: Guidelines have concluded that there is a great need for new models of integrated care, e.g., heart failure and palliative care, in order to facilitate equality of care for dying patients, regardless of diagnosis. We found no evidence in the literature concerning the advantages and effects of integrated heart failure and palliative advanced home care for patients with severe chronic heart failure. AIM: The primary aim is to study the effects of integrated Palliative advanced homecarRE and heart FailurE caRE (PREFER) on patients' symptom burden, quality of life, and activities of daily living (ADL) as compared to usual care. METHOD: Prospective, randomized study with an open-evaluation PROBE design. Optimally treated outpatients with chronic heart failure of varying aetiologies in New York Heart Association classes III-IV will be eligible to participate. CONCLUSION: The PREFER study is designed to investigate whether a new concept of managing patients with severe chronic heart failure by integrating palliative homecare and active heart failure treatment will reduce symptom burden, increase quality of life and ADL, and reduce the number of hospitalizations in patients with severe chronic heart failure.

Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators.

Used appropriately, biomarkers improve the assessment of respiratory tract infections and sepsis. Most prominently, circulating procalcitonin levels increase by a factor of several tens of thousands during sepsis. Using a sensitive assay, procalcitonin safely and markedly reduces antibiotic usage in respiratory tract infections and nonbacterial meningitis. Procalcitonin is the protopye of hormokine mediators. The term "hormokine" encompasses the cytokine-like behaviour of hormones during inflammation and infections. The concept is based on a ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Other peptides share some features of hormokines, e.g. natriuretic peptide and copeptin. Hormokines are not only biomarkers of infection but are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. However, at increased levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralisation of hormokines during infection was shown to improve survival, and thus might open new treatment options for severe infections, especially of the respiratory tract.