Safety and Efficacy of SGLT2 Inhibitors: A Multiple-Treatment Meta-Analysis of Clinical Decision Indicators

To jointly assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiorenal outcomes and all-cause mortality in type 2 diabetes mellitus (T2DM) with or at high risk of cardiovascular disease (CVD). We performed a systematic review and network meta-analysis, systematically searching the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science databases up to September 2020. Primary outcomes were composite major adverse cardiovascular events (MACEs), hospitalization for heart failure, all-cause mortality and a composite renal outcome. We performed a random effects network meta-analysis estimating the pooled hazard ratio (HR), risk ratio and number needed to treat (NNT). Six trials evaluating empagliflozin, canagliflozin, dapagliflozin and ertugliflozin met the inclusion/exclusion criteria, which comprised 46,969 patients, mostly with established CVD. Pooled estimates (95% CI) of benefits of SGLT2i in terms of HR and NNT were as follows: for all-cause mortality, 0.85 (0.75, 0.97) and 58 (28, 368); for MACE, 0.91 (0.85, 0.97) and 81 (44, 271); for hospitalization for heart failure, 0.70 (0.62, 0.78) and 32 (20, 55); and for composite renal outcome, 0.61 (0.50, 0.74) and 20 (11, 44). Pooled estimates for serious adverse events were 0.92 (95% CI 0.89, 0.95). In patients with T2DM at cardiovascular risk, ertugliflozin is a less potent drug than empagliflozin, canagliflozin or dapagliflozin to prevent cardiorenal events and all-cause mortality. In addition, our data endorse that empagliflozin is the best treatment option among SGLT2i for this type of patient, but the evidence is not consistent enough.

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The Effects of SGLT2 Inhibitors on Cardiovascular and Renal Outcomes in Diabetic Patients: A Systematic Review and Meta-Analysis

Cardiorenal Medicine ◽

10.1159/000503919 ◽

2019 ◽

Vol 10 (1) ◽

pp. 1-10 ◽

Cited By ~ 16

Author(s):

Kevin Bryan Lo ◽

Fahad Gul ◽

Pradhum Ram ◽

Aaron Y. Kluger ◽

Kristen M. Tecson ◽

...

Keyword(s):

Heart Failure ◽

Fixed Effects ◽

Meta Analysis ◽

Renal Outcome ◽

Major Adverse Cardiovascular Events ◽

Diabetic Patients ◽

Number Needed To Treat ◽

Atherosclerotic Cardiovascular Disease ◽

Renal Outcomes ◽

All Cause Mortality

Background: Previous meta-analyses demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) primarily on patients with established atherosclerotic cardiovascular disease (ASCVD), but with questionable efficacy on patients at risk of ASCVD. Additionally, evidence of beneficial cardiorenal outcomes in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with the CV outcomes trials remains unclear. Canagliflozin, one of the SGLT2i, has recently been studied in a large randomized controlled trial in diabetic patients with chronic kidney disease. Thus, there is a need to understand the combined outcomes on the population targeted for treatment with SGLT2i as a whole, regardless of ASCVD status. This meta-analysis will therefore assess the efficacy of SGLT2i in cardiovascular and renal outcomes in general, and in patients with eGFR under 60 mL/min/1.73 m2 in particular. Methods: We searched PubMed and Cochrane databases for randomized, placebo-controlled studies involving SGLT2i. We examined composite cardiovascular outcomes of death from cardiovascular causes, nonfatal myocardial infarctions, nonfatal stroke, and heart failure hospitalizations. Renal composite outcomes and progression of albuminuria were also analyzed. Pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated using a fixed-effects model. Results: The search yielded a total of 252 articles. Four studies were ultimately included in the meta-analysis after exclusion of other irrelevant studies. The pooled RR (95% CI) for the composite cardiovascular outcome was 0.93 (0.87–0.99) with a number needed to treat (NNT) of 167 in the general study population and 0.89 (0.77–1.02) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for all-cause mortality was 0.9 (0.84–0.97) with NNT = 143. The pooled RR for death from cardiovascular causes alone was 0.89 (0.81–0.99) in the general population and 0.82 (0.62–1.07) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for heart failure hospitalizations was 0.71 (0.63–0.79) with NNT = 91. With respect to renal outcomes, the pooled RR for the composite renal outcome was 0.63 (0.56–0.71) with NNT = 67; this was true even in patients with eGFR <60 mL/min/1.73 m2 0.67 (0.59–0.76). Lastly, the pooled RR for progression of albuminuria was 0.80 (0.76–0.84). Conclusion: SGLT2i are associated with significantly lower major adverse cardiovascular events, heart failure hospitalizations, and all-cause mortality. The evidence is strongest in reducing heart failure hospitalizations. However, the evidence is weaker when it comes to the population subset with eGFR <60 mL/min/1.73 m2. SGLT2i are also associated with significantly lower adverse renal events, with these effects apparent even in the population with eGFR <60 mL/min/1.73 m2.

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Ivabradine added to usual care in patients with heart failure: a systematic review with meta-analysis and trial sequential analysis

BMJ evidence-based medicine ◽

10.1136/bmjebm-2021-111724 ◽

2021 ◽

pp. bmjebm-2021-111724

Author(s):

Mathias Maagaard ◽

Emil Eik Nielsen ◽

Naqash Javaid Sethi ◽

Ning Liang ◽

Si-Hong Yang ◽

...

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Usual Care ◽

Sequential Analysis ◽

Meta Analysis ◽

Risk Of Bias ◽

Trial Sequential Analysis ◽

Serious Adverse Events ◽

All Cause Mortality

ObjectivesTo assess the beneficial and harmful effects of adding ivabradine to usual care in participants with heart failure.DesignA systematic review with meta-analysis and trial sequential analysis.Eligibility criteriaRandomised clinical trials comparing ivabradine and usual care with usual care (with or without) placebo in participants with heart failure.Information sourcesMedline, Embase, CENTRAL, LILACS, CNKI, VIP and other databases and trial registries up until 31 May 2021.Data extractionPrimary outcomes were all-cause mortality, serious adverse events and quality of life. Secondary outcomes were cardiovascular mortality, myocardial infarction and non-serious adverse events. We performed meta-analysis of all outcomes. We used trial sequential analysis to control risks of random errors, the Cochrane risk of bias tool to assess the risks of systematic errors and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of the evidence.ResultsWe included 109 randomised clinical trials with 26 567 participants. Two trials were at low risk of bias, although both trials were sponsored by the company that developed ivabradine. All other trials were at high risk of bias. Meta-analyses and trial sequential analyses showed that we could reject that ivabradine versus control reduced all-cause mortality (risk ratio (RR)=0.94; 95% CI 0.88 to 1.01; p=0.09; high certainty of evidence). Meta-analysis and trial sequential analysis showed that ivabradine seemed to reduce the risk of serious adverse events (RR=0.90; 95% CI 0.87 to 0.94; p<0.00001; number needed to treat (NNT)=26.2; low certainty of evidence). This was primarily due to a decrease in the risk of ‘cardiac failure’ (RR=0.83; 95% CI 0.71 to 0.97; p=0.02; NNT=43.9), ‘hospitalisations’ (RR=0.89; 95% CI 0.85 to 0.94; p<0.0001; NNT=36.4) and ‘ventricular tachycardia’ (RR=0.59; 95% CI 0.43 to 0.82; p=0.001; NNT=212.8). However, the trials did not describe how these outcomes were defined and assessed during follow-up. Meta-analyses showed that ivabradine increased the risk of atrial fibrillation (RR=1.19; 95% CI 1.04 to 1.35; p=0.008; number needed to harm (NNH)=116.3) and bradycardia (RR=3.95; 95% CI 1.88 to 8.29; p=0.0003; NNH=303). Ivabradine seemed to increase quality of life on the Kansas City Cardiomyopathy Questionnaire (KCCQ) (mean difference (MD)=2.92; 95% CI 1.34 to 4.50; p=0.0003; low certainty of evidence), but the effect size was small and possibly without relevance to patients, and on the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) (MD=−5.28; 95% CI −6.60 to −3.96; p<0.00001; very low certainty of evidence), but the effects were uncertain. Meta-analysis showed no evidence of a difference between ivabradine and control when assessing cardiovascular mortality and myocardial infarction. Ivabradine seemed to increase the risk of non-serious adverse events.Conclusion and relevanceHigh certainty evidence shows that ivabradine does not seem to affect the risks of all-cause mortality and cardiovascular mortality. The effects on quality of life were small and possibly without relevance to patients on the KCCQ and were very uncertain for the MLWHFQ. The effects on serious adverse events, myocardial infarction and hospitalisation are uncertain. Ivabradine seems to increase the risk of atrial fibrillation, bradycardia and non-serious adverse events.PROSPERO registration number: CRD42018112082.

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Influenza vaccination in patients with heart failure: a systematic review and meta-analysis of observational studies

Heart ◽

10.1136/heartjnl-2019-315193 ◽

2019 ◽

Vol 106 (5) ◽

pp. 350-357 ◽

Cited By ~ 11

Author(s):

Bárbara Sucena Rodrigues ◽

Cláudio David ◽

João Costa ◽

Joaquim J Ferreira ◽

Fausto J Pinto ◽

...

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Influenza Vaccination ◽

Influenza Infection ◽

Meta Analysis ◽

Risk Of Bias ◽

Control Group ◽

High Morbidity ◽

Cochrane Central Register ◽

All Cause Mortality

ObjectiveDespite the progression of treatments over decades, heart failure (HF) is a disease with high morbidity, mortality and economic burden. Influenza infection is an important trigger for cardiovascular (CV) events, including HF. Influenza vaccination has been seen to reduce the risk of CV mortality in patients with coronary disease, but the effect in patients with HF is still unclear. Therefore, we conducted a systematic review to evaluate the effect of influenza vaccination in the morbimortality of patients with HF.MethodsMEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Health Technology Assessment and PsycINFO databases (December 2018) were searched for longitudinal studies evaluating influenza vaccination compared with a non-vaccination control group in patients with HF. The risk of bias was assessed according to the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled HRs with 95% CIs, and heterogeneity was evaluated using the I2 statistics.ResultsSix cohort studies evaluating 179 158 patients with HF were included in the meta-analysis. Influenza vaccination was associated with a lower risk of all-cause mortality (HR=0.83; 95% CI 0.76 to 0.91; I2=75%). The effect of the influenza vaccination was not statistically significant in a pooled analysis of CV mortality (HR=0.92, 95% CI 0.73 to 1.15; 2 studies) and of all-cause hospitalisations (HR=1.01, 95% CI 0.92 to 1.11; 2 studies). The majority of outcomes in the included studies had a serious risk of bias and almost all evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation (GRADE) evidence.ConclusionsInfluenza vaccination was associated with a significant decrease in all-cause mortality risk in patients with HF.

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The Effects of Dapagliflozin in Patients With Heart Failure Complicated With Type 2 Diabetes: A Meta-Analysis of Placebo-Controlled Randomized Trials

Frontiers in Clinical Diabetes and Healthcare ◽

10.3389/fcdhc.2021.703937 ◽

2021 ◽

Vol 2 ◽

Author(s):

Miaobo Zhai ◽

Xin Du ◽

Changmei Liu ◽

Huipu Xu

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Meta Analysis ◽

Cardiovascular Death ◽

Major Adverse Cardiovascular Events ◽

Significant Heterogeneity ◽

Sodium Glucose Cotransporter ◽

All Cause Mortality ◽

Incidence Of Hospitalization

BackgroundCardiovascular disease threatens the health and quality of life of individuals, particularly those with type II diabetes. Recently, some studies have reported the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the rates of hospitalization or urgent visits, resulting in IV therapy for heart failure in patients with type 2 diabetes mellitus (T2DM).MethodsWe did a comprehensive search in electronic databases from inception through July 2020 for randomized-controlled trials, using the keywords “sodium-glucose cotransporter-2 inhibitor”, “dapagliflozin”, “heart failure”, “cardiovascular outcomes”, “major adverse cardiovascular events”, “all-cause mortality”, and “cardiovascular death”. Random-effects summary odds ratios (OR) were constructed using M-L heterogeneity model.ResultsFive trials with 5,252 patients were ultimately included. The incidence of hospitalization for heart failure (HHF) (n=4, OR=0.74; 95% CI, 0.61 to 0.88; I2 = 0%) and all-cause mortality (ACM, n=4, OR=0.76; 95% CI, 0.66 to 0.94; I2 = 0%); was reduced by dapagliflozin, respectively, in all heart failure patients, without obvious heterogeneity. The incidence of cardiovascular death in dapagliflozin was lower than that in placebo without statistically significant (CVD, n=5, OR=0.84; 95% CI, 0.69 to 1.03; I2 = 0%). In HFrEF subgroup, dapagliflozin was associated with a reduced incidence of hospitalization for heart failure (n=4, OR=0.74; 95% CI, 0.60 to 0.91; I2 = 0%), cardiovascular death (n=4, OR=0.72; 95% CI, 0.58 to 0.91; I2 = 8%), and all-cause mortality (n=3, OR=0.70; 95% CI, 0.50 to 0.99; I2 = 43%) without significant heterogeneity. In contrast, in the HFpEF subgroup, there was no difference in the incidence of cardiovascular death (n=2, OR=1.45; 95% CI, 0.95 to 2.22; I2 = 0%) and all-cause mortality (n=2, OR=1.04; 95% CI, 0.76 to 1.43; I2 = 0%) between dapagliflozin and placebo.ConclusionIn our study, dapagliflozin performed a statistical reduction in the rate of heart failure hospitalization, cardiovascular death, and all-cause mortality in patients with HFrEF and diabetes. However, in the HFpEF subgroup, dapagliflozin did not show a significant cardiovascular protective effect.

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sGC Stimulators for Heart Failure: A Meta-Analysis of Randomized Controlled Trials

10.21203/rs.3.rs-116054/v1 ◽

2020 ◽

Author(s):

Xueli Shi ◽

Xuejing Yu ◽

Jinhui Wang ◽

Jianzhong Zhou

Keyword(s):

Heart Failure ◽

Randomized Controlled Trials ◽

Cardiovascular Events ◽

Meta Analysis ◽

Controlled Trials ◽

Serious Adverse Events ◽

Randomized Controlled ◽

Significant Difference ◽

All Cause Mortality ◽

Sgc Stimulators

Abstract Background Oral sGC stimulators are novel treatments for heart failure (HF). Since individual studies are limited to confirm the efficacy and safety of sGC stimulators in patients with HF, we provide a meta-analysis based on published clinical randomized controlled trials. Methods Embase, PubMed, Cochrane and Medline were applied to search for randomized controlled trials (published before March 29, 2020 without language restrictions) by comparing oral sGC stimulators to placebos. Main endpoints were efficacy outcomes, including all-cause mortality, incidence of cardiovascular-events related death or hospitalization, alterations of EQ-5D index, and N-terminal (NT)-pro hormone BNP(NT-proBNP); and safety outcomes included incidence of serious adverse events (SAEs), symptomatic hypotension and syncope. Results Six trials were enrolled (N=6255 participants), sGC stimulators yielded a lower incidence of cardiovascular-events related death or hospitalization (OR=0.88, 95% CI=0.79 to 0.98), an improvement in EQ-5D scores (SMD=0.44, 95% CI=0.24 to 0.63), and a lower relative risk of SAEs (OR=0.90, 95% CI=0.81 to 1.00) compared with placebos. Furthermore, NT-proBNP was decreased by riociguat (SMD=-0.79, 95% CI=-1.10 to -0.49), but not by vericiguat (SMD=0.04, 95% CI=-0.18 to 0.25). There was no significant difference in all-cause mortality (OR=0.95, 95% CI=0.83 to 1.09), incidence of symptomatic hypotension (OR=1.15, 95% CI=0.95 to 1.40) and syncope (OR=1.15, 95% CI=0.87 to 1.53) between sGC stimulators and placebos. Conclusion Oral sGC stimulators may be beneficial for HF with a good tolerance, further studies are also needed to establish the optimal approach in clinical practice.

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Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0040-1716874 ◽

2020 ◽

Vol 46 (08) ◽

pp. 908-918

Author(s):

Behnood Bikdeli ◽

Saurav Chatterjee ◽

Ajay J. Kirtane ◽

Sahil A. Parikh ◽

Giuseppe M. Andreozzi ◽

...

Keyword(s):

Pulmonary Embolism ◽

Cardiovascular Mortality ◽

Dermatan Sulfate ◽

Meta Analysis ◽

Arterial Disease ◽

Controlled Trials ◽

Cochrane Central Register ◽

Bleeding Events ◽

Random Effects Models ◽

All Cause Mortality

AbstractThrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52–0.85, p = 0.001), cardiovascular mortality (OR 0.44, 95% CI 0.22–0.89, p = 0.02), and MI (OR 0.70, 95% CI 0.51–0.96, p = 0.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45–1.35, p = 0.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24–0.81, p = 0.008), including DVT (OR 0.41, 95% CI 0.26–0.65, p < 0.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40–2.15, p = 0.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47–2.74, p = 0.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.

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Long-Term and Short-Term Prognostic Value of Circulating Soluble Suppression of Tumorigenicity-2 Concentration in Chronic Heart Failure: A Systematic Review and Meta-Analysis

Cardiology ◽

10.1159/000509660 ◽

2021 ◽

pp. 1-8

Author(s):

Guoqi Dong ◽

Hao Chen ◽

Hongru Zhang ◽

Yihuang Gu

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Prognostic Value ◽

Web Of Science ◽

Meta Analysis ◽

Short Term ◽

Prisma Statement ◽

All Cause Mortality ◽

Increasing Risk

Introduction: Soluble suppression of tumorigenicity-2 (sST2) has been considered as a prognostic factor of cardiovascular disease. However, the prognostic value of sST2 concentration in chronic heart failure remains to be summarized. Methods: We searched PubMed, Embase, and Web of Science for eligible studies up to January 1, 2020. Data extracted from articles and provided by authors were used in agreement with the PRISMA statement. The endpoints were all-cause mortality (ACM), cardiovascular mortality (CVM)/heart failure-related hospitalization (HFH), and all-cause mortality (ACM)/heart failure-related readmission (HFR). Results: A total of 11 studies with 5,121 participants were included in this analysis. Higher concentration of sST2 predicted the incidence of long-term ACM (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02–1.04), long-term ACM/HFR (HR: 1.42, CI: 1.27–1.59), and long-term CVM/HFH (HR: 2.25, CI: 1.82–2.79), regardless of short-term ACM/HFR (HR: 2.31, CI: 0.71–7.49). Conclusion: Higher sST2 concentration at baseline is associated with increasing risk of long-term ACM, ACM/HFR, and CVM/HFH and can be a tool for the prognosis of chronic heart failure.

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Prediction of all-cause mortality with malnutrition assessed by controlling nutritional status score in patients with heart failure: a systematic review and meta-analysis

Public Health Nutrition ◽

10.1017/s1368980021002470 ◽

2021 ◽

pp. 1-8

Author(s):

Huiyang Li ◽

Peng Zhou ◽

Yikai Zhao ◽

Huaichun Ni ◽

Xinping Luo ◽

...

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Nutritional Status ◽

Meta Analysis ◽

Predictive Values ◽

Increased Risk ◽

Patients With Heart Failure ◽

All Cause Mortality ◽

Conut Score

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.

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Comparative effectiveness of bisoprolol and carvedilol among patients receiving maintenance hemodialysis

Clinical Kidney Journal ◽

10.1093/ckj/sfaa248 ◽

2021 ◽

Author(s):

Ping-Hsun Wu ◽

Yi-Ting Lin ◽

Jia-Sin Liu ◽

Yi-Chun Tsai ◽

Mei-Chuan Kuo ◽

...

Keyword(s):

Heart Failure ◽

Ischemic Stroke ◽

Lower Risk ◽

Cox Model ◽

Major Adverse Cardiovascular Events ◽

Maintenance Hemodialysis ◽

Risk Of Death ◽

Relative Safety ◽

Dialysis Vintage ◽

All Cause Mortality

Abstract Background Despite widespread use, there is no trial evidence to inform β-blocker’s (BB) relative safety and efficacy among patients undergoing hemodialysis (HD). We herein compare health outcomes associated with carvedilol or bisoprolol use, the most commonly prescribed BBs in these patients. Methods We created a cohort study of 9305 HD patients who initiated bisoprolol and 11 171 HD patients who initiated carvedilol treatment between 2004 and 2011. We compared the risk of all-cause mortality and major adverse cardiovascular events (MACEs) between carvedilol and bisoprolol users during a 2-year follow-up. Results Bisoprolol initiators were younger, had shorter dialysis vintage, were women, had common comorbidities of hypertension and hyperlipidemia and were receiving statins and antiplatelets, but they had less heart failure and digoxin prescriptions than carvedilol initiators. During our observations, 1555 deaths and 5167 MACEs were recorded. In the multivariable-adjusted Cox model, bisoprolol initiation was associated with a lower all-cause mortality {hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.60–0.73]} compared with carvedilol initiation. After accounting for the competing risk of death, bisoprolol use (versus carvedilol) was associated with a lower risk of MACEs [HR 0.85 (95% CI 0.80–0.91)] and attributed to a lower risk of heart failure [HR 0.83 (95% CI 0.77–0.91)] and ischemic stroke [HR 0.84 (95% CI 0.72–0.97)], but not to differences in the risk of acute myocardial infarction [HR 1.03 (95% CI 0.93–1.15)]. Results were confirmed in propensity score matching analyses, stratified analyses and analyses that considered prescribed dosages or censored patients discontinuing or switching BBs. Conclusions Relative to carvedilol, bisoprolol initiation by HD patients was associated with a lower 2-year risk of death and MACEs, mainly attributed to lower heart failure and ischemic stroke risk.

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Efficacy and Safety of Oral Anticoagulants in Patients with Systolic Heart Failure in Sinus Rhythm: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Cohort Studies

TH Open ◽

10.1055/s-0040-1720961 ◽

2020 ◽

Vol 04 (04) ◽

pp. e383-e392

Author(s):

Marie H. Nygaard ◽

Anne-Mette Hvas ◽

Erik L. Grove

Keyword(s):

Heart Failure ◽

Sinus Rhythm ◽

Cohort Studies ◽

Antiplatelet Therapy ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomized Controlled ◽

All Cause Mortality

Abstract Introduction There is conflicting evidence on the risk–benefit ratio of oral anticoagulants (OAC) in heart failure (HF) patients without atrial fibrillation. We aimed to evaluate the efficacy and safety of OAC in HF patients in sinus rhythm. Methods A systematic literature search was conducted using PubMed and Embase. We included randomized controlled trials (RCT) and cohort studies, comparing OAC with antiplatelet or no treatment/placebo in patients with HF. Outcomes evaluated were stroke, myocardial infarction (MI), all-cause mortality, and major bleeding. Results Five RCTs and three cohort studies were included. OAC was associated with a reduced risk of ischemic stroke when compared with no treatment/placebo (odds ratio [OR] = 0.67, 95% confidence interval [CI]: [0.47, 0.94]) and antiplatelet therapy (OR = 0.55, 95% CI: [0.37, 0.81]). No significant reduction was found in MI, when OAC was compared with no treatment/placebo (OR = 0.82, 95% CI: [0.63, 1.07]) or antiplatelet therapy (OR = 1.04, 95% CI: [0.60, 1.81]). The all-cause mortality analysis showed no significant reduction when comparing OAC with no treatment/placebo (OR = 0.99, 95% CI: [0.87, 1.12]) or antiplatelet therapy (OR = 1.00, 95% CI: [0.86, 1.16]). The nonsignificant effect of OAC on all-cause mortality was supported by a meta-analysis of the three cohort studies (OR = 1.02, 95% CI: [0.75, 1.38]). Patients treated with OAC had a significantly higher risk of major bleeding than patients receiving antiplatelet therapy (OR = 2.16, 95% CI: [1.55, 3.00]) and a numerically higher risk when compared with no treatment/placebo (OR = 2.38, 95% CI: [0.87, 6.49]). Conclusion The present study does not support the routine use of OAC in patients with HF in sinus rhythm.

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