scholarly journals Cardiovascular and mortality benefits of sodium–glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jordi Real ◽  
Bogdan Vlacho ◽  
Emilio Ortega ◽  
Joan Antoni Vallés ◽  
Manel Mata-Cases ◽  
...  

Abstract Background Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium–glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. Methods CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). Results After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47–0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31–0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47–0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52–0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54–0.80; p < 0.001). Conclusions In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

Author(s):  
Gerasimos Filippatos ◽  
Stefan D. Anker ◽  
Rajiv Agarwal ◽  
Luis M. Ruilope ◽  
Peter Rossing ◽  
...  

Background: Chronic kidney disease (CKD) and type 2 diabetes (T2D) are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. These prespecified analyses from FIGARO-DKD assessed the impact of finerenone on clinically important HF outcomes. Methods: Patients with T2D and albuminuric CKD (urine albumin-to-creatinine ratio [UACR] ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] ≥25 to ≤90 ml/min/1.73 m 2 , or UACR ≥300 to ≤5000 mg/g and eGFR ≥60 ml/min/1.73 m 2 ,), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first event outcomes included: new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators). Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI 0.50-0.93]; P =0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including a 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI 0.70-0.95]; P =0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI 0.56-0.90]; P =0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52- 0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups. Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with CKD and T2D, irrespective of a history of HF.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Noergaard ◽  
C Torp-Pedersen ◽  
P Vestergaard ◽  
N Wong ◽  
T Gerds ◽  
...  

Abstract Background Two promising classes of second-line glucose-lowering drugs, the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have both been shown to lower the risk of cardiovascular (CV) outcomes in patients with type 2 diabetes, however no head-to-head comparisons exist. Purpose The aim of this study was to examine the risk of CV and all-cause mortality, incident chronic kidney disease (CKD) and hospitalisation for heart failure (HF) in association with SGLT-2i versus GLP-1RA use. Methods New users of SGLT-2i and GLP-1RA, with no prior use of drugs from the comparison class, were identified between 2012–2016, using individual-level linkage of Danish nationwide registries. The absolute risk of CV was calculated using the Aalen-Johansen Estimator with non-CV mortality as competing risk. The hazard ratios (HR) of CV and all-cause mortality, incident CKD and hospitalisation for HF were estimated using Cox regression and adjusted for age, sex, diabetes duration and other outcome specific risk factors. Results The study included a total of 8,304 SGLT-2i users (median age: 63 years [interquartile range (IQR): 54–70], males: 63%, dapagliflozin: 60.5%, empagliflozin: 36.5%) and 13,318 GLP-1RA users (median age: 60 years [IQR: 50–68], males: 54%, liraglutide: 97.4%) with a median follow-up time of 2.0 [(IQR): 1.5–2.9] years and 3.6 [IQR: 2.1–5.0] years, respectively. At baseline 29% of SGLT-2i and 30% of GLP-1RA users had CV disease. The absolute risks are shown in Figure 1. Compared with GLP-1RA, initiation of SGLT-2i was in adjusted analyses associated with a lower risk of CV mortality (HR: 0.49 [confidence interval (CI): 0.37–0.65]), all-cause mortality [HR: 0.79 [CI: 0.68–0.93], incident CKD (HR: 0.42 [CI: 0.34–0.53] and hospitalisation for HF (HR: 0.68 [CI: 0.59–0.78]). Figure 1 Conclusion SGLT-2i use was associated with a significantly lower risk of CV and all-cause mortality, incident CKD and hospitalisation for HF in comparison with GLP-1RA use. Acknowledgement/Funding The Danish Heart Foundation (18-R125-A8381-22082)


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1130-P
Author(s):  
JINGWEI LI ◽  
BRUCE NEAL ◽  
HIDDO L. HEERSPINK ◽  
CLARE ARNOTT ◽  
CHRISTOPHER CANNON ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 27-OR
Author(s):  
JINGWEI LI ◽  
MEG J. JARDINE ◽  
BRUCE NEAL ◽  
HIDDO L. HEERSPINK ◽  
CHRISTOPHER CANNON ◽  
...  

2021 ◽  
Vol 32 ◽  
pp. 100739
Author(s):  
Claire A Lawson ◽  
Samuel Seidu ◽  
Francesco Zaccardi ◽  
Gerry McCann ◽  
Umesh T Kadam ◽  
...  

Author(s):  
Gerasimos Filippatos ◽  
Stefan D. Anker ◽  
Rajiv Agarwal ◽  
Bertram Pitt ◽  
Luis M. Ruilope ◽  
...  

Background: The FIDELIO-DKD trial evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and CV outcomes. We report the effect of finerenone on individual CV outcomes and in patients with and without history of atherosclerotic CV disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with T2D and urine albumin-to-creatinine ratio 30-5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m 2 , treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite CV outcome included time to CV death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified CV analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Results: Between September 2015 and June 2018, 13,911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite CV outcome compared with placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.99; P=0.034), with no significant interaction between patients with and without CVD (HR, 0.85; 95% CI, 0.71-1.01 in patients with a history of CVD; HR, 0.86; 95% CI, 0.68-1.08 in patients without a history of CVD; P-value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone vs 0.8% with placebo in patients with CVD and 2.2% with finerenone vs 1.0% with placebo in patients without CVD). Conclusions: Among patients with CKD and T2D, finerenone reduced incidence of the composite CV outcome, with no evidence of differences in treatment effect based on pre-existing CVD status. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02540993 (Funded by Bayer AG)


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