A Review of the Role of Type 2 Diabetes and SGLT2 Inhibitors in Heart Failure with Preserved Ejection Fraction

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Gladys I. Palaguachi ◽  
William Frishman
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Sglt2 Inhibitors ◽  
Preserved Ejection Fraction

223-OR: Heart Failure with Reduced, Midrange and Preserved Ejection Fraction in Chinese with Type 2 Diabetes: Risk Factors and Prognosis

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 223-OR
Author(s):  
ANDREA LUK ◽  
XINGE ZHANG ◽  
ERIK FUNG ◽  
HONGJIANG WU ◽  
ERIC S. LAU ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Diabetes Risk ◽  
Preserved Ejection Fraction ◽  
Diabetes Risk Factors

scholarly journals MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jesper Jensen ◽  
Morten Schou ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Tine W. Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Natriuretic Peptides ◽  
Continuous Variable ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Definition Of

Abstract Background Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

1407Drug effect of luseogliflozin and voglibose on heart failure with preserved ejection fraction in diabetic patients: a multicenter randomized-controlled trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Ejiri ◽  
T Miyoshi ◽  
H Kihara ◽  
Y Hata ◽  
T Nagano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Abstract Background Recent randomized, placebo-controlled trial in patients with type 2 diabetes demonstrated that the sodium-glucose cotransporter 2 inhibitors reduced mortality, cardiovascular events and hospitalization for heart failure. However, those trials were not specialized design to investigate the effect of sodium-glucose cotransporter 2 inhibitors in patients with heart failure, in particular with heart failure with preserved ejection fraction. Purpose The aim of this study was to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) in type 2 diabetes patients with heart failure with preserved ejection fraction. Methods This study was a prospective, multicenter, open-label, randomized-controlled trial, comparing luseogliflozin 2.5 mg once daily or voglibose 0.2 mg three times daily in patients with type 2 diabetes suffering from heart failure with preserved ejection fraction (left ventricular ejection fraction >45% and BNP ≥35 pg/ml2) in a 1:1 randomization fashion. Randomization was undertaken using a computer-generated random sequence web response system. The primary outcome was the difference from baseline in BNP after 12 weeks of treatment between two drugs. The key secondary outcomes were the change from baseline in left ventricular ejection fraction and E/e' in echocardiographic parameters, body weight, glycohemoglobin level after 12 weeks of treatment. The safety outcomes included the incidence of major adverse cardiovascular events, hypoglycemic adverse events, and urinary tract infection. Results Between December 2015 and September 2018, 173 patients from 16 hospitals and clinics have been included in this study. Of those, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in the BNP concentration after 12 weeks from baseline between the two groups; the ratio of the average values at week 12 to the baseline value was 0.91 in the luseoglifllzin group as compared with 0.98 in the voglibose group (percent change, −9.0% vs. −1.9%, ratio of change with luseogliflozin vs. voglibose, 0.93; 95% confidence interval, 0.78 to 1.10; p=0.26). The key secondary outcomes including left ventricular ejection fraction, E/e', body weight, glycohemoglobin level and the safety outcomes did not differ significantly between the two groups. Conclusions In type 2 diabetes patients with heart failure with preserved ejection fraction, the administration of luseogliflozin did not lead to a significant reduction in the BNP concentration than that of voglibose. Left ventricular ejection fraction, E/e', body weight and glycohemoglobin level after 12 weeks of treatment, comparing with at baseline did not differ significantly between the two groups. (UMIN Clinical Trial Registry number, UMINehz748.005618395) Acknowledgement/Funding Novartis

scholarly journals Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261986
Author(s):  
Ning Li ◽  
Guowei Zhou ◽  
Yawei Zheng ◽  
Dan Lv ◽  
Xiangjun Zhu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Ejection Fraction ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Atherosclerotic Cardiovascular Disease ◽  
Reduced Ejection Fraction ◽  
Stage 4

Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR<30mL/min per 1.73m2) and underlying diseases (Type 2 diabetes, heart failure (Preserved ejection fraction or reduced ejection fraction), atherosclerotic cardiovascular disease) were used to stratify efficacy and safety outcomes. The results were subjected to a sensitivity analysis to ensure that they were reliable. Results In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

scholarly journals Type 2 diabetes and heart failure: Characteristics and prognosis in preserved, mid-range and reduced ventricular function

2018 ◽  
Vol 15 (6) ◽  
pp. 494-503 ◽  
Author(s):  
Isabelle Johansson ◽  
Ulf Dahlström ◽  
Magnus Edner ◽  
Per Näsman ◽  
Lars Rydén ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction

Objective: To study the characteristics and prognostic implications of type 2 diabetes in different heart failure entities from a nationwide perspective. Methods: This observational study comprised 30,696 heart failure patients prospectively included in the Swedish Heart Failure Registry (SwedeHF) 2003–2011 from specialist care, with mortality information available until December 2014. Patients were categorized into three heart failure entities by their left ventricular ejection fraction (heart failure with preserved ejection fraction: ⩾50%, heart failure with mid-range ejection fraction: 40%–49% and heart failure with reduced ejection fraction: <40%). All-cause mortality stratified by type 2 diabetes and heart failure entity was studied by Cox regression. Results: Among the patients, 22% had heart failure with preserved ejection fraction, 21% had heart failure with mid-range ejection fraction and 57% had heart failure with reduced ejection fraction. The proportion of type 2 diabetes was similar, ≈25% in each heart failure entity. Patients with type 2 diabetes and heart failure with preserved ejection fraction were older, more often female and burdened with hypertension and renal impairment compared with heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction patients among whom ischaemic heart disease was more common. Type 2 diabetes remained an independent mortality predictor across all heart failure entities after multivariable adjustment, somewhat stronger in heart failure with left ventricular ejection fraction below 50% (hazard ratio, 95% confidence interval; heart failure with preserved ejection fraction: 1.32 [1.22–1.43], heart failure with mid-range ejection fraction: 1.51 [1.39–1.65], heart failure with reduced ejection fraction: 1.46 [1.39–1.54]; p-value for interaction, p = 0.0049). Conclusion: Type 2 diabetes is an independent mortality predictor across all heart failure entities increasing mortality risk by 30%–50%. In type 2 diabetes, the heart failure with mid-range ejection fraction entity resembles heart failure with reduced ejection fraction in clinical characteristics, risk factor pattern and prognosis.

scholarly journals Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Shigeru Toyoda ◽  
Takumi Imai ◽  
Kazuki Shiina ◽  
Hirofumi Tomiyama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Left Ventricular Ejection ◽  
Glucose Lowering

Abstract Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents. Methods This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents. Results Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup. Conclusion The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015

Sign in / Sign up

Export Citation Format

Share Document