scholarly journals Influence of receptor selectivity on benefits from SGLT2 inhibitors in patients with heart failure: a systematic review and head-to-head comparative efficacy network meta-analysis

Author(s):  
Tobias Täger ◽  
Lutz Frankenstein ◽  
Dan Atar ◽  
Stefan Agewall ◽  
Norbert Frey ◽  
...  

Abstract Background Receptor selectivity of sodium-glucose cotransporter-2 inhibitors (SGLT2i) varies greatly between agents. The overall improvement of cardiovascular (CV) outcomes in heart failure (HF) patients varies between trials. We, therefore, evaluated the comparative efficacy of individual SGLT2i and the influence of their respective receptor selectivity thereon. Methods We identified randomized controlled trials investigating the use of SGLT2i in patients with HF—either as the target cohort or as a subgroup of it. Comparators included placebo or any other active treatment. The primary endpoint was the composite of hospitalization for HF or CV death. Secondary outcomes included all-cause mortality, CV mortality, hospitalization for HF, worsening renal function (RF), and the composite of worsening RF or CV death. Evidence was synthesized using network meta-analysis. In addition, the impact of receptor selectivity on outcomes was analysed using meta-regression. Results We identified 18,265 patients included in 22 trials. Compared to placebo, selective and non-selective SGLT2i improved fatal and non-fatal HF events. Head-to-head comparisons suggest superior efficacy with sotagliflozin as compared to dapagliflozin, empagliflozin or ertugliflozin. No significant difference was found between canagliflozin and sotagliflozin. Meta-regression analyses show a decreasing benefit on HF events with increasing receptor selectivity of SGLT2i. In contrast, receptor selectivity did not affect mortality and renal endpoints and no significant difference between individual SGLT2i was noted. Conclusion Our data point towards a class-effect of SGLT2i on mortality and renal outcomes. However, non-selective SGLT2i such as sotagliflozin may be superior to highly selective SGLT2i in terms of HF outcomes.

2021 ◽  
pp. 1-8
Author(s):  
Huiyang Li ◽  
Peng Zhou ◽  
Yikai Zhao ◽  
Huaichun Ni ◽  
Xinping Luo ◽  
...  

Abstract Objective: The aim of this meta-analysis was to investigate the association between malnutrition assessed by the controlling nutritional status (CONUT) score and all-cause mortality in patients with heart failure. Design: Systematic review and meta-analysis. Settings: A comprehensively literature search of PubMed and Embase databases was performed until 30 November 2020. Studies reporting the utility of CONUT score in prediction of all-cause mortality among patients with heart failure were eligible. Patients with a CONUT score ≥2 are grouped as malnourished. Predictive values of the CONUT score were summarized by pooling the multivariable-adjusted risk ratios (RR) with 95 % CI for the malnourished v. normal nutritional status or per point CONUT score increase. Participants: Ten studies involving 5196 patients with heart failure. Results: Malnourished patients with heart failure conferred a higher risk of all-cause mortality (RR 1·92; 95 % CI 1·58, 2·34) compared with the normal nutritional status. Subgroup analysis showed the malnourished patients with heart failure had an increased risk of in-hospital mortality (RR 1·78; 95 % CI 1·29, 2·46) and follow-up mortality (RR 2·01; 95 % CI 1·58, 2·57). Moreover, per point increase in CONUT score significantly increased 16% risk of all-cause mortality during the follow-up. Conclusions: Malnutrition defined by the CONUT score is an independent predictor of all-cause mortality in patients with heart failure. Assessment of nutritional status using CONUT score would be helpful for improving risk stratification of heart failure.


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.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Agata Bielecka-Dabrowa ◽  
Ibadete Bytyçi ◽  
Stephan Von Haehling ◽  
Stefan Anker ◽  
Jacek Jozwiak ◽  
...  

Abstract Background The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. Methods We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. Results Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.


Author(s):  
Paolo Mastandrea

AbstractHeart failure with normal ejection fraction (HFNEF) accounts for approximately 50% of heart failure (HF) cases. To establish the utility of brain natriuretic peptide (BNP) in differentiating HF-related severe dyspnea from non-HF-related acute dyspnea, we used an estimation formula (eF) that was obtained from a series of three meta-regressions. We selected 60 out of 2721 case-control and follow-up studies that were published from 1998 to 2010. The heart failure levels (HFLs) were assessed using the New York Heart Association (NYHA) criteria. Random-effects meta-regression analyses of the natural logarithm (ln) of the BNP odds ratio (OR) were performed on the HFLs. The ln of the median BNP values (lnmBNP) was meta-regressed over the laboratory method (LM). A third meta-regression was performed on the HFLs to account for only the lnmBNP in the homogeneous LM subgroups. To determine the eF, the data from the diseased and control subjects were combined. The Bland-Altman method was used to detect eF bias. The overall BNP(OR) in the subgroup with severe HF was 35. The lnmBNP analysis showed that LM was a significant heterogeneity factor in the meta-regression (slope −0.38; CI −0.59 to −0.16). The meta-regression of lnmBNP on the HFL resulted in the following calculation for eF: estimated HFL (eHFL)=(lnmBNP–3.157)/0.886. The Bland-Altman test revealed no significant difference (0.0997; 95% CI −2.84 to 3.06) between HFL and eHFL. The severe eHFL showed a 78% accuracy. Based on the eF obtained from this meta-analysis, the BNP outcomes were shown to reliably diagnose severe dyspnea in HF and differentiate this condition from non-HF acute dyspnea.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Indraratna ◽  
D Tardo ◽  
J Yu ◽  
K Delbaere ◽  
M Brodie ◽  
...  

Abstract Introduction Cardiovascular disease (CVD) remains the leading cause of death in the world. Mobile phones have become ubiquitous in most developed societies. Smartphone applications, telemonitoring and clinician-driven short message service (SMS) allow for novel methods in managing chronic cardiovascular conditions such as ischaemic heart disease, heart failure and hypertension. Purpose To evaluate the impact of mobile phone-based interventions (MPIs) on mortality, hospitalisations and blood pressure and body mass index (BMI) in patients diagnosed with either acute coronary syndrome, heart failure or hypertension. Methods A systematic review was conducted using seven electronic databases, identifying all randomised control trials (RCTs) featuring an MPI in the management of these conditions. Meta-analysis was performed by using standard analytical techniques. The odds ratio (OR) was used as a summary statistic. Results Twenty-six RCTs including 6,713 patients were identified. Of these 26 studies, 13 examined text messaging intereventions, 10 studied telemonitoring interventions and three described smartphone applications with other functions. Twelve studies were included for meta-analysis. In patients with heart failure (n=1683), MPIs were associated with a significantly lower rate of all-cause hospital admissions at six months (31% vs. 36%, OR 0.77, 95% CI 0.62–0.97, p=0.03, I2 = 0). A significant difference was also demonstrated for heart-failure admissions (14.0% vs. 18.5%, OR 0.69, 95% CI 0.48 to 0.98, p=0.04, I2 = 26%). There was no difference in mortality (10.4% vs. 11.6% p=0.45). In patients with hypertension, the difference in systolic BP was 4.3mmHg less in the intervention group (95% CI: −7.8 to −0.78 mmHg, p=0.02). Four studies examined medication compliance as an endpoint in patients with ischaemic heart disease, and all four demonstrated a significant difference favouring the MPI group (see table 1). However, due to variable quantification of compliance, meta-analysis was not possible. There was no significant difference in the change in BMI from four studies after six or more months (mean difference −0.46, 95% CI: −1.44 to 0.52, P=0.36). Conclusions The available data suggests MPIs may have a role as valuable adjuncts in the management of chronic CVD. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Health and Medical Research Council (NHMRC)


2019 ◽  
Vol 23 (25) ◽  
pp. 1-98 ◽  
Author(s):  
Rod S Taylor ◽  
Sarah Walker ◽  
Oriana Ciani ◽  
Fiona Warren ◽  
Neil A Smart ◽  
...  

Background Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups. Objectives (1) To obtain definitive estimates of the impact of ExCR interventions compared with no exercise intervention (control) on mortality, hospitalisation, exercise capacity and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, sex, left ventricular ejection fraction, HF aetiology, New York Heart Association class and baseline exercise capacity; and (3) to assess whether or not the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation and HRQoL), and determine if this is an acceptable surrogate end point. Design This was an individual participant data (IPD) meta-analysis. Setting An international literature review. Participants HF patients in randomised controlled trials (RCTs) of ExCR. Interventions ExCR for at least 3 weeks compared with a no-exercise control, with 6 months’ follow-up. Main outcome measures All-cause and HF-specific mortality, all-cause and HF-specific hospitalisation, exercise capacity and HRQoL. Data sources IPD from eligible RCTs. Review methods RCTs from the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH/ExTraMATCH II) IPD meta-analysis and a 2014 Cochrane systematic review of ExCR (Taylor RS, Sagar VA, Davies EJ, Briscoe S, Coats AJ, Dalal H, et al. Exercise-based rehabilitation for heart failure. Cochrane Database Syst Rev 2014;4:CD003331). Results Out of the 23 eligible RCTs (4398 patients), 19 RCTs (3990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time-to-event estimates in favour of ExCR, although confidence intervals (CIs) were wide: all-cause mortality had a hazard ratio (HR) of 0.83 (95% CI 0.67 to 1.04); HF-related mortality had a HR of 0.84 (95% CI 0.49 to 1.46); all-cause hospitalisation had a HR of 0.90 (95% CI 0.76 to 1.06); and HF-related hospitalisation had a HR of 0.98 (95% CI 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared with the control, improvements were seen in the 6-minute walk test (6MWT) (mean 21.0 m, 95% CI 1.57 to 40.4 m) and Minnesota Living with Heart Failure Questionnaire score (mean –5.94, 95% CI –1.0 to –10.9; lower scores indicate improved HRQoL) at 12 months’ follow-up. No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation (R 2 trial > 50% and p > 0.50) between peak oxygen uptake (VO2peak) or the 6MWT with mortality and HRQoL were seen. The estimated surrogate threshold effect was an increase of 1.6 to 4.6 ml/kg/minute for VO2peak. Limitations There was a lack of consistency in how included RCTs defined and collected the outcomes: it was not possible to obtain IPD from all includable trials for all outcomes and patient-level data on exercise adherence was not sought. Conclusions In comparison with the no-exercise control, participation in ExCR improved the exercise and HRQoL in HF patients, but appeared to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. VO2peak and 6MWT may be suitable surrogate end points for the treatment effect of ExCR on mortality and HRQoL in HF. Future studies should aim to achieve a consensus on the definition of outcomes and promote reporting of a core set of HF data. The research team also seeks to extend current policies to encourage study authors to allow access to RCT data for the purpose of meta-analysis. Study registration This study is registered as PROSPERO CRD42014007170. Funding The National Institute for Health Research Health Technology Assessment programme.


2021 ◽  
Author(s):  
Junpeng Xu ◽  
Ruixiang Zeng ◽  
Xiaoyi Mai ◽  
Wenjun Pan ◽  
Yuzhuo Zhang ◽  
...  

Abstract BackgroundAccumulating evidence suggests that HbA1c levels, a common clinical indicator of chronic glucose metabolism over the preceding 2-3 months, are independent risk factor for cardiovascular disease, including heart failure. The aim of this protocol is to conduct a systematic review and meta-analysis to assess the possible predictive value of HbA1c on mortality and readmission in patients with heart failure.MethodsA systematic and comprehensive search will be performed using PubMed, Embase, Central and other databases before August 2021 to identify relevant trials. All-cause mortality is the pre-specified primary endpoint. Cardiovascular death and heart failure readmission are secondary interested endpoints. We will only include prospective and retrospective cohort trials and place no restrictions on the language, race, region and publication period. The Newcastle-Ottawa Scale will be used to assess the quality of each trial included. If there are sufficient trials, we will conduct meta-analysis with pooled relative risks and corresponding 95% confidence interval to evaluate the possible predictive value of HbA1c on mortality and readmission. Otherwise, we will undertake a narrative synthesis. Heterogeneity and publication bias will be assessed. If heterogeneity is significant among included trails, a sensitivity analysis or subgroup analysis will be used to explore the source of heterogeneity, such as diverse types of heart failure or patients with diabetes and non-diabetes. Also, we will conduct meta-regression to examine the time-effect and treatment-effect modifiers on all-cause mortality compared between different quantile of HbA1c levels. Finally, a restricted cubic spline model may be used to explore the dose-response relationship between HbA1c and adverse outcomes.DiscussionThis planned analysis is anticipated to identify the predictive value of HbA1c on mortality and readmission in patients with heart failure. Improved understanding of different HbA1c levels and their specific effect on diverse types of heart failure or patients with diabetes and non-diabetes is expected to be figured out. Also, a dose-response relationship or optimal range of HbA1c will be determined to instruct clinicians and patients.PROSPERO registration detailsCRD42021276067


2019 ◽  
Vol 105 (6) ◽  
pp. 2068-2080 ◽  
Author(s):  
Tou-Yuan Tsai ◽  
Yu-Kang Tu ◽  
Kashif M Munir ◽  
Shu-Man Lin ◽  
Rachel Huai-En Chang ◽  
...  

Abstract Context The evidence of whether hypothyroidism increases mortality in the elderly population is currently inconsistent and conflicting. Objective The objective of this meta-analysis is to determine the impact of hypothyroidism on mortality in the elderly population. Data Sources PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched from inception until May 10, 2019. Study Selection Studies evaluating the association between hypothyroidism and all-cause and/or cardiovascular mortality in the elderly population (ages ≥ 60 years) were eligible. Data Extraction Two reviewers independently extracted data and assessed the quality of the studies. Relative risk (RR) was retrieved for synthesis. A random-effects model for meta-analyses was used. Data Synthesis A total of 27 cohort studies with 1 114 638 participants met the inclusion criteria. Overall, patients with hypothyroidism experienced a higher risk of all-cause mortality than those with euthyroidism (pooled RR = 1.26, 95% CI: 1.15-1.37); meanwhile, no significant difference in cardiovascular mortality was found between patients with hypothyroidism and those with euthyroidism (pooled RR = 1.10, 95% CI: 0.84-1.43). Subgroup analyses revealed that overt hypothyroidism (pooled RR = 1.10, 95% CI: 1.01-1.20) rather than subclinical hypothyroidism (pooled RR = 1.14, 95% CI: 0.92-1.41) was associated with increased all-cause mortality. The heterogeneity primarily originated from different study designs (prospective and retrospective) and geographic locations (Europe, North America, Asia, and Oceania). Conclusions Based on the current evidence, hypothyroidism is significantly associated with increased all-cause mortality instead of cardiovascular mortality among the elderly. We observed considerable heterogeneity, so caution is needed when interpreting the results. Further prospective, large-scale, high-quality studies are warranted to confirm these findings.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Marlena Schnieder ◽  
Anneki von Glasenapp ◽  
Amelie Hesse ◽  
Marios N. Psychogios ◽  
Mathias Bähr ◽  
...  

The impact of heart failure on outcome in stroke patients is not fully understood. There is evidence for an increased mortality and morbidity, but it remains uncertain whether thrombectomy in patients with large vessel occlusion (LVO) in the anterior circulation is less effective in patients with heart failure compared to patients without. Retrospectively, we analyzed echocardiographic data of all patients in our stroke database, who underwent mechanical thrombectomy (n=668) for the presence of heart failure. Furthermore, we collected baseline characteristics and neurological and neuroradiological parameters. In the analysis, 373 of the 668 patients of our stroke database underwent echocardiography. Of these 373 patients, 90 patients (24%) suffered from heart failure with reduced left ventricular ejection fraction measured by echocardiography according to the current guidelines. After adjustment for age, the Alberta stroke program early CT score (ASPECTS), and time from symptom onset to recanalization, the analysis revealed that thrombectomy in patients with heart failure and LVO is not associated with less favorable outcome measured by the modified Rankin Scale after 90 days (3 (0-6) vs. 3 (1-5); p=0.380). Moreover, we could not find a significant difference in mortality compared to patients without heart failure (11.0% vs. 7.4%; p=0.313).


Author(s):  
Ahmad Hazem ◽  
Sunita Sharma ◽  
Amit Sharma ◽  
Cameron Leitch ◽  
Roopalakshmi Sharadanant ◽  
...  

Importance: Right bundle branch block (RBBB) is observed in approximately 5-14% of patients with heart failure (HF). Multiple observational studies have reported the association of RBBB with clinical outcomes in patients with HF. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with HF. Data Sources: We have systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts that described all cause or cardiovascular mortality in patients with RBBB and HF. We excluded studies that reported unadjusted outcome, i.e.: unadjusted event rates. Knowledge synthesis: We pooled reported risk ratio and hazard ratio. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: We found 12 relevant observational studies enrolling over 38,000 patients. Risk of bias was assessed using the Newcastle-Ottawa Scale. Included studies had at least a moderate quality. Seven of those evaluated prognosis of patients with RBBB and heart failure. After a mean follow up period of 2.5 years (range: 1-5 years), RBBB was associated with a statistically significant increased risk of all-cause mortality compared to patients with heart failure but no BBB, RR 1.27, 95% CI (1.08-1.50), Figure 1. The other 5 studies evaluated CHF patients receiving cardiac resynchronization therapy (CRT), comparing outcomes of patients with RBBB to those with LBBB. After a mean f/u period of 3 years, patients with RBBB were once again found to have an increased risk of all-cause mortality, RR 1.45, 95% CI 1.12-1.89. Conclusion and Relevance: RBBB in patients with HF is associated with higher all-cause mortality in comparison to patients without inter-ventricular conduction defects, as well as LBBB patients in patients undergoing CRT setting.


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