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Open accessJournal ArticleDOI: 10.1002/EJHF.2131

Use of Sodium‐Glucose Co‐transporter 2 Inhibitors in Patients with Heart Failure and Type 2 Diabetes Mellitus: Data from the Swedish Heart Failure Registry

02 Mar 2021-European Journal of Heart Failure (John Wiley & Sons, Ltd)-Vol. 23, Iss: 6, pp 1012-1022
Abstract: Aims Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use. Methods and results Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52-0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all-cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke. Conclusion In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity.

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Topics: Type 2 diabetes (54%), Heart failure (53%), Hazard ratio (53%) ... show more
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6 results found


Open accessJournal ArticleDOI: 10.1016/J.DIABRES.2021.108796
Abstract: Sodium-glucose transporter-2 inhibitors (SGLT2i), originally launched as glucose-lowering drugs, have been studied in large cardiovascular outcome trials to ascertain safety. Surprisingly, these compounds reduced the risk of cardiovascular events (cardiovascular death, non-fatal myocardial and non-fatal stroke) and total mortality. The mechanisms behind this benefit are only partly understood, but a major contributor is the reduction of heart failure hospitalisations, evident already within weeks after the initiation of the SGLT2i. SGLT2 inhibition increases urinary glucose excretion, thereby improving glycaemic control in an insulin-independent manner. Moreover, SGLT2i potentially impact the cardiovascular system both indirectly via weight loss and blood pressure lowering and directly through osmotic diuresis and increased sodium excretion and presumably by improving myocardial energetics. The aim of this review is to summarise evidence from all major outcome trials investigating SGLT2i in patients with diabetes, as well as recent evidence from trials in heart failure patients without glucose perturbations, which pave the way for novel treatment of large groups of patients. The results of these studies have been taken into account in recently issued guidelines for the management of diabetes and cardiovascular disease. An important task for diabetologists, cardiologists and general practitioners is to incorporate them into clinical practice to the benefit of many patients.

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Topics: Type 2 diabetes (52%), Diabetes mellitus (52%), Heart failure (52%)

2 Citations


Open accessJournal ArticleDOI: 10.1016/J.IJCARD.2021.09.013
Chris J. Kapelios, Marco Canepa1, Lina Benson2, Camilla Hage3  +4 moreInstitutions (4)
Abstract: Background Patients with heart failure (HF) are often cared for by non-cardiologists. The implications are unknown. Methods In a nationwide HF cohort with reduced ejection fraction (HFrEF), we compared demographics, clinical characteristics, guideline-based therapy use and outcomes in non-cardiology vs. cardiology in-patient and out-patient care. Results Between 2000 and 2016, 36,076 patients with HFrEF were enrolled in the Swedish HF registry (19,337 [54%] in-patients), with 44% of in-patients and 45% of out-patients managed in non-cardiology settings. Predictors of treatment in non-cardiology were age > 75 years (adjusted odds ratio for non-cardiology 1.20; 95% confidence interval 1.14–1.27), lower education level (0.71; 0.66–0.76 for university vs. compulsory), valve disease (1.24; 1.18–1.31) and systolic blood pressure (SBP) >120 mmHg (1.05; 1.00–1.10). Non-cardiology care was significantly associated with lower use of beta-blockers (0.80; 0.74–0.86) and devices (intracardiac defibrillator [ICD] and/or cardiac resynchronization therapy [CRT]: 0.63; 0.56–0.71), and less frequent specialist follow-up (0.61; 0.57–0.65). Over 1-year follow-up the risk of all-cause mortality (adjusted hazard ratio 1.09; 1.03–1.15) was higher but the risk of first HF (re-) hospitalization was lower (0.93; 0.89–0.97) in non-cardiology vs. cardiology care. Conclusions In HFrEF, non-cardiology care was independently associated with older age, lower education and lower income. After covariate adjustment, non-cardiology care was associated with lower use of beta-blockers and devices, higher mortality, and lower risk of HF hospitalization. Access to cardiology caremay not be equitable and this may have implications for use of guideline-based care and outcomes.

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Topics: Lower risk (52%), Ejection fraction (52%), Guideline (51%) ... show more

1 Citations



Open accessJournal ArticleDOI: 10.1007/S10741-021-10186-7
Abstract: Diabetic patients frequently develop heart failure with preserved (HFpEF) or mid-range (HFmEF) cardiac ejection fractions. This condition may be secondary to diabetic cardiomyopathy or one of several relevant comorbidities, mainly hypertension. Several mechanisms link diabetes to HFpEF or HFmEF. Among these, non-enzymatic glycation of interstitial proteins, lipotoxicity, and endothelial dysfunction may promote structural damage and ultimate lead to heart failure. Findings from several large-scale trials indicated that treatment with sodium/glucose cotransporter 2 inhibitors (SGLT2-iss) resulted in significant improvements in cardiovascular outcomes in diabetic patients with high cardiovascular risk. However, there is currently some evidence that suggests a clinical advantage of using SGLT2-iss specifically in cases of HFpEF or HFmEF. Preclinical and clinical studies revealed that SGLT2-iss treatment results in a reduction in left ventricular mass and improved diastolic function. While some of the beneficial effects of SGLT2-iss have already been characterized (e.g., increased natriuresis and diuresis as well as reduced blood pressure, plasma volume, and arterial stiffness, and nephron-protective activities), there is increasing evidence suggesting that SGLT2-iss may have direct actions on the heart. These findings include SGLT2-iss-mediated reductions in the expression of hypertrophic foetal genes and diastolic myofilaments stiffness, increases in global phosphorylation of myofilament regulatory proteins (in HFpEF), inhibition of cardiac late sodium channel current and Na+/H+ exchanger activity, metabolic shifts, and effects on calcium cycling. Preliminary data from previously published studies suggest that SGLT2-iss could be useful for the treatment of HFpEF and HFmEF. Several large ongoing trials, including DELIVER AND EMPEROR -preserved have been designed to evalute the efficacy of SGLT2-iss in improving clinical outcomes in patients diagnosed with HFpEF. The goal of this manuscript is to review the use of SGLT2-iss inhibitors for HFpEF or HFmEF associated with diabetes.

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Topics: Diabetic cardiomyopathy (56%), Heart failure (56%), Ejection fraction (53%) ... show more


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31 results found


Open accessJournal ArticleDOI: 10.1056/NEJMOA1504720
Bernard Zinman1, Christoph Wanner2, John M. Lachin3, David Fitchett2  +8 moreInstitutions (4)
Abstract: BACKGROUND The effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.)

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Topics: Empagliflozin (70%), Relative risk reduction (54%), Cause of death (52%) ... show more

5,890 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA1611925
Bruce Neal, Vlado Perkovic1, Vlado Perkovic2, Kenneth W. Mahaffey3  +7 moreInstitutions (5)
Abstract: BackgroundCanagliflozin is a sodium–glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. MethodsThe CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. ResultsThe mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% c...

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Topics: Canagliflozin (61%), Gliflozin (57%), Type 2 diabetes (53%) ... show more

3,546 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA1812389
Declare–Timi Investigators1Institutions (1)
Abstract: Background The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. Methods We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. Results We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, ...

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Topics: Dapagliflozin (60%), Type 2 diabetes (53%), Diabetes mellitus (53%) ... show more

2,197 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA1811744
Vlado Perkovic1, Vlado Perkovic2, Meg Jardine2, Meg Jardine3  +27 moreInstitutions (18)
Abstract: Background Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium...

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Topics: Type 2 Diabetes Mellitus (64%), Canagliflozin (61%), Nephropathy (59%) ... show more

1,825 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA1911303
Abstract: Background In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-ind...

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Topics: Dapagliflozin (59%), Ejection fraction (58%), Heart failure (56%) ... show more

1,797 Citations