scholarly journals Digoxin–mortality: randomized vs. observational comparison in the DIG trial

2019 ◽  
Vol 40 (40) ◽  
pp. 3336-3341 ◽  
Author(s):  
Lukas Aguirre Dávila ◽  
Kristina Weber ◽  
Udo Bavendiek ◽  
Johann Bauersachs ◽  
Janet Wittes ◽  
...  

Abstract Aims The Digitalis Investigation Group (DIG) trial, the only large randomized trial of digoxin in heart failure, reported a neutral effect on mortality and a significant reduction in heart failure hospitalizations. Recent observational studies reported increased mortality with digoxin treatment. We present further analyses of the DIG trial displaying the inability to control bias in observational treatment comparisons despite extensive statistical adjustments. Methods and results Forty-four percent of the 6800 patients in the DIG trial had been treated with digoxin before randomization, and half of them were randomly withdrawn from digoxin treatment. We contrast the main randomization-based result of the DIG trial with the observational non-randomized comparison of patients pre-treated or not pre-treated with digoxin. Mortality [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.12–1.34; P < 0.001] and heart failure hospitalizations (HR 1.47, 95% CI 1.33–1.61; P < 0.001) were significantly higher in patients pre-treated with digoxin even after adjustment for baseline population differences. The higher risks for both outcomes in those who had previously received digoxin persisted even if they received placebo during the trial (HR 1.24, 95% CI 1.10–1.40; P < 0.001). This sharply contradicts the neutral effect on mortality and the significant reduction in heart failure hospitalizations observed in the randomized comparison. Conclusion Prescription of digoxin is an indicator of disease severity and worse prognosis, which cannot be fully accounted for by covariate adjustments in the DIG trial where patients were well-characterized. It is unlikely that weaker research approaches (observational studies of administrative data or registries) can provide more reliable estimates of the effects of cardiac glycosides.

2010 ◽  
Vol 56 (6) ◽  
pp. 944-951 ◽  
Author(s):  
Tobias Reichlin ◽  
Thenral Socrates ◽  
Patrick Egli ◽  
Mihael Potocki ◽  
Tobias Breidthardt ◽  
...  

Abstract Background: Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF). Methods: We prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses. Results: MPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited [area under the ROC curve (AUC) 0.53] and inferior to that of BNP (AUC 0.95, P &lt; 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO &gt;99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (≤99 vs &gt;99 pmol/L) and BNP (median of ≤847 vs &gt;847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P &lt; 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045). Conclusions: MPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.


Perfusion ◽  
2020 ◽  
pp. 026765912098222
Author(s):  
Yu Wang ◽  
Tengfei Qiao ◽  
Jun Zhou

Purpose: Type A acute aortic dissection (AAD) is an uncommon catastrophic cardiovascular disease with high pre-hospital mortality rate without timely and effectively treated. The aim of this study was to assess the value of serum platelet to hemoglobin (PHR) in predicting in-hospital mortality in type A AAD patients. Methods: A total of 183 type A AAD patients were included in this retrospective investigation from January 2017 to December 2019. Admission blood routine parameters were gathered and PHR was computed. The outcome was all-cause in-hospital mortality within 30 days. Results The average levels of serum PHR were significant higher in survivor group than those in non-survivor group (1.14 ± 0.57 vs 0.87 ± 0.47, p = 0.006) and serum PHR was an independent factor associated with in-hospital mortality (hazard ratio (HR): 2.831; 95% confidence interval (CI): 1.108–7.231; p = 0.030). ROC noted that 0.8723 was chosen as the ideal cutoff value with a sensitivity of 64.3% and specificity of 72.5%. In addition, the area under the ROC curve (AUC) was 0.693 (95% CI 0.599–0.787, p < 0.001). Conclusion: Admission serum PHR can be used as an independent predictor of in-hospital mortality in patients with type A AAD.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Kamisaka ◽  
K Kamiya ◽  
K Iwatsu ◽  
N Iritani ◽  
Y Iida ◽  
...  

Abstract Background Weight loss (WL) has been considered as a prognostic factor in heart failure with reduced ejection fraction (HFrEF). However, the prognosis and associated factors of WL in heart failure with preserved ejection fraction (HFpEF) have remained unclear. Purpose This study aimed to examine the prevalence, prognosis, and clinical characteristics of worse prognosis based on the identified WL after discharge in HFpEF. Methods The study was conducted as a part of a multicenter cohort study (Flagship). The cohort study enrolled ambulatory HF who hospitalized due to acute HF or exacerbation of chronic HF. Patients with severe cognitive, psychological disorders or readmitted within 6-month after discharge were excluded in the study. WL was defined as ≥5% weight loss in 6-month after discharge and HFpEF was defined as left ventricular ejection fraction (LVEF) ≥50% at discharge. Age, gender, etiology, prior HF hospitalization, New York Heart Association (NYHA) class, brain natriuretic peptide (BNP) or N-terminal-proBNP (NT-proBNP), anemia (hemoglobin; male &lt;13g/dL, female &lt;12g/dL), serum albumin, Geriatric Depression Scale, hand grip strength and comorbidities were collected at discharge. Patients were stratified according to their body mass index (BMI) at discharge as non-obese (BMI &lt;25) or obese (BMI ≥25). We analyzed the association between WL and HF rehospitalization from 6 month to 2 years after discharge using Kaplan-Meier curve analysis and Cox regression analysis adjusted for age and gender, and clinical characteristics associated to worse prognosis in WL using logistic regression analysis adjusted for potential confounders in HFpEF. Results A total of 619 patients with HFpEF were included in the analysis. The prevalence of WL was 12.9% in 482 non-obese and 15.3% in 137 obese patients. During 2 years, 72 patients were readmitted for HF (non-obese: 48, obese: 24). WL in non-obese independently associated with poor prognosis (hazard ratio: 2.2: 95% confidence interval: 1.13–4.25) after adjustment for age and sex, while WL in obese patients did not. Logistic regression analysis chose age (odds ratio 1.02 per 1 year; 1.00–1.05), anemia (2.14; 1.32–3.48), and BNP ≥200pg/mL or NT-proBNP ≥900pg/mL (1.83; 1.18–2.86) as independent associated factors for worse prognosis of WL in non-obese patients. Conclusion In HFpEF, WL in early after discharge in non-obese elderly patients may be a prognostic indicator for HF rehospitalization. HF management including WL prevention along with controlling anemia is likely to improve prognosis in this population. Kaplan Meier survival curves Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): A Grant-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science


Author(s):  
Tsuyoshi Yamabe ◽  
Yanling Zhao ◽  
Paul A Kurlansky ◽  
Suzuka Nitta ◽  
Saveliy Kelebeyev ◽  
...  

Abstract OBJECTIVES Chronic kidney disease (CKD) is prevalent in patients undergoing cardiovascular surgery, and it negatively impacts procedural outcomes; however, its influence on the outcomes of aortic surgery has not been well studied. This study aims to elucidate the importance of CKD on the outcomes of aortic root replacement (ARR). METHODS Patients who underwent ARR between 2005 and 2019 were retrospectively reviewed (n = 882). Patients were divided into 3 groups based on the Kidney Disease: Improving Global Outcomes criteria: Group 1 [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2, n = 421); Group 2 (eGFR = 30–59 ml/min/1.73 m2, n = 424); and Group 3 (eGFR &lt; 30 ml/min/1.73 m2, n = 37). To reduce potential confounding, a propensity score matching was also performed between Group 1 and the combined group of Group 2 and Group 3. The primary end point was 10-year survival. Secondary end points were in-hospital mortality and perioperative morbidity. RESULTS Severe CKD patients presented with more advanced overall chronic and acute illnesses. Kaplan–Meier analysis showed a significant correlation between CKD stage and 10-year survival (log-rank P &lt; 0.001). The number of events for Group 1 was 15, Group 2 was 49 and Group 3 was 11 in 10 years. Group 3 had significantly higher in-hospital mortality (13.5% vs 3.5% in Group 2 vs 0.7% in Group 1, P &lt; 0.001) and stroke (8.1% vs 7.1% vs 1.2%, P &lt; 0.001) as well as introduction to new dialysis (27.0% vs 5.4% vs 1.7%, P &lt; 0.001). eGFR was shown to be an independent predictor of mortality (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99). Comparison between propensity matched groups showed similar postoperative outcomes, and eGFR was still identified as a predictor of mortality (hazard ratio, 0.97; 95% confidence interval, 0.95–0.99). CONCLUSIONS Higher stage in CKD negatively impacts the long-term survival in patients who are undergoing ARR.


2013 ◽  
Vol 33 (4) ◽  
pp. 411-418 ◽  
Author(s):  
Yun Li ◽  
Lihua Zhang ◽  
Yong Gu ◽  
Chuanming Hao ◽  
Tongying Zhu

BackgroundInsulin resistance is associated with multiple risk factors for cardiovascular (CV) disease in the general population. Patients on peritoneal dialysis (PD) are more likely to develop insulin resistance. However, no evaluation of the impact of insulin resistance on CV disease morbidity or mortality in patients on PD has been performed.MethodsOur prospective cohort study included all non-diabetic patients on PD at our center ( n = 66). Insulin resistance was evaluated at baseline by the homeostasis model assessment method (HOMA-IR) using fasting glucose and insulin levels. The cohort was followed for up to 58 months (median: 41.3 months; interquartile range: 34.3 months). A multivariate Cox model was used to analyze the impact of insulin resistance on CV disease mortality.ResultsFourteen CV events occurred in the higher HOMA-IR group [IR-H (HOMA-IR values in the range 2.85 – 19.5), n = 33], but only one event occurred in the lower HOMA-IR group (IR-L (HOMA-IR values in the range 0.83 – 2.71), n = 33) during the follow-up period. Level of HOMA-IR was a significant predictor of CV events [risk ratio: 17.7; 95% confidence interval (CI): 2.10 to 149.5; p = 0.008]. In the IR-H group, 10 patients died (8 CV events), but in the IR-L group, only 4 patients died (1 CV event). Patients in the IR-H group experienced significantly higher CV mortality (hazard ratio: 9.02; 95% CI: 1.13 to 72.2; p = 0.04). Even after adjustments for age, systolic blood pressure, body mass index, C-reactive protein, triglycerides, resistin, and leptin, HOMA-IR remained an independent predictor of CV mortality (hazard ratio: 14.8; 95% CI: 1.22 to 179.1; p = 0.03).ConclusionsInsulin resistance assessed using HOMA-IR was an independent predictor of CV morbidity and mortality in a cohort of nondiabetic patients on PD. Insulin resistance is a modifiable risk factor; the reduction of insulin resistance may reduce CV risk and improve survival in this group of patients.


2022 ◽  
Vol 12 ◽  
Author(s):  
Chenglin Duan ◽  
Jingjing Shi ◽  
Guozhen Yuan ◽  
Xintian Shou ◽  
Ting Chen ◽  
...  

Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer’s disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations.Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK’s Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results.Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 &gt; 0.05; weighted median (WM), p = 0.337 &gt; 0.05; inverse variance weighted (IVW), p = 0.471 &gt; 0.05; simple mode, p = 0.454 &gt; 0.05; weighted mode, p = 0.401 &gt; 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 &gt; 0.05; IVW, p = 0.0879 &gt; 0.05; simple mode, p = 0.170 &gt; 0.05; weighted mode, p = 0.110 &gt; 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 &lt; 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis.Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zhuo-Ming Huang ◽  
Wen-Rong Chen ◽  
Qi-Wen Su ◽  
Zhuo-Wen Huang

Background: The metabolic syndrome (MS) is significantly associated with the risk of incident heart failure (HF). However, there are still great controversies about the impact of MS on the prognosis in patients with established HF. This meta-analysis aimed to ascertain the effect of MS on the prognosis in patients with HF.Methods: We searched multiple electronic databases, including PubMed, Opengrey, EMBASE, and Cochran Library, for potential studies up to February 15, 2021. Observational studies that reported the impact of MS on the prognosis in patients with established HF were included for meta-analysis.Results: Ten studies comprising 18,590 patients with HF were included for meta-analysis. The median follow-up duration of the included studies was 2.4 years. Compared with HF patients without MS, the risk of all-cause mortality and cardiovascular mortality was not increased in HF with MS (HR = 1.04, 95% CI = 0.88–1.23 for all-cause mortality; HR = 1.66, 95% CI = 0.56–4.88 for cardiovascular mortality, respectively). However, there was a significant increase in composited cardiovascular events in the HF patients with MS compared with those without MS (HR = 1.73, 95% CI = 1.23–2.45).Conclusions: In patients with established HF, the presence of MS did not show an association on the risk of all-cause mortality or cardiovascular mortality, while it may increase the risk of composite cardiovascular events.


2020 ◽  
Vol 6 ◽  
Author(s):  
Oren Caspi ◽  
Doron Aronson

The use of opioids in acute pulmonary oedema is considered standard therapy by many physicians. The immediate relieving effect of morphine on the key symptomatic discomfort associated with acute heart failure, dyspnoea, facilitated the categorisation of morphine as a beneficial treatment in this setting. During the last decade, several retrospective studies raised concerns regarding the safety and efficacy of morphine in the setting of acute heart failure. In this article, the physiological effects of morphine on the cardiovascular and respiratory systems are summarised, as well as the potential clinical benefits and risks associated with morphine therapy. Finally, the reported clinical outcomes and adverse event profiles from recent observational studies are discussed, as well as future perspectives and potential alternatives to morphine in the setting of acute heart failure.


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