Heart Failure Hospitalization or Cardiovascular Death with Empagliflozin in Patients with Type 2 Diabetes and High Cardiovascular Risk: Analysis Over Time in EMPA-REG OUTCOME

2016 ◽  
Vol 40 (5) ◽  
pp. S42
Author(s):  
Philippe Vand E. Borne ◽  
Jyothis George ◽  
Jisoo Lee ◽  
Michaela Mattheus ◽  
Hans Jurgen Woerle ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Ailing Zhang ◽  
Xufei Luo ◽  
Haiyang Meng ◽  
Jian Kang ◽  
Guijun Qin ◽  
...  

AimTo evaluate the impact of sodium glucose cotransporter 2 inhibitors (SGLT-2i) on risk of heart failure hospitalization in patients with type 2 diabetes.MethodsWe searched the PubMed, Embase, The Cochrane Library, CNKI, Wanfang, CBM, and other web knowledge databases for data from randomized controlled trials. We performed statistical analyses by using review Manager (RevMan) 5.3 and STATA 12.0 for meta-analysis.ResultsEight randomized controlled trials that compared SGLT-2i versus placebo met our inclusion criteria and were included in the study. The final meta-analysis included a total of 55,763 type 2 diabetes patients. Compared with placebo, SGLT-2i reduced the risk of heart failure hospitalization (RR, 0.63; 95% CI, 0.53 to 0.74; P < 0.00001), MACE (defined as cardiovascular death, myocardial infarction, or ischemic stroke) (RR, 0.92; 95% CI, 0.86 to 0.98; P < 0.007), cardiovascular death (RR, 0.78; 95%CI, 0.62 to 0.99; P = 0.04) in type 2 diabetes patients. SGLT-2i could reduce the risk of death from any cause (RR, 0.77; 95% CI, 0.59 to 1.01; P = 0.06) without statistical significance in type 2 diabetes patients.ConclusionCompared with placebo, SGLT-2i may reduce the risk of heart failure hospitalization, MACE, and cardiovascular death. Therefore, SGLT-2i may be an ideal choice for type 2 diabetes mellitus patient with heart failure. These results will help inform practitioners, patients, and authorities making appropriate choices in hypoglycemic therapy clinical practice.


Author(s):  
Taha Sen ◽  
Jingwei Li ◽  
Brendon L. Neuen ◽  
Clare Arnott ◽  
Bruce Neal ◽  
...  

Background Studies have suggested that sodium glucose co‐transporter 2 inhibitors exert anti‐inflammatory effects. We examined the association of baseline growth differentiation factor‐15 (GDF‐15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with type 2 diabetes in the CANVAS (Canagliflozin Cardiovascular Assessment Study) and determined the effect of the sodium glucose co‐transporter 2 inhibitor canagliflozin on circulating GDF‐15. Methods and Results The CANVAS trial randomized 4330 people with type 2 diabetes at high cardiovascular risk to canagliflozin or placebo. The association between baseline GDF‐15 and cardiovascular (non‐fatal myocardial infarction, non‐fatal stroke, cardiovascular death), HF, and kidney (40% estimated glomerular filtration rate decline, end‐stage kidney disease, renal death) outcomes was assessed using multivariable adjusted Cox regression models. During median follow‐up of 6.1 years (N=3549 participants with available samples), 555 cardiovascular, 129 HF, and 137 kidney outcomes occurred. Each doubling in baseline GDF‐15 was significantly associated with a higher risk of cardiovascular (hazard ratio [HR], 1.2; 95% CI, 1.0‒1.3), HF (HR, 1.5; 95% CI, 1.2‒2.0) and kidney (HR, 1.5; 95% CI, 1.2‒2.0) outcomes. Baseline GDF‐15 did not modify canagliflozin’s effect on cardiovascular, HF, and kidney outcomes. Canaglifozin treatment modestly lowered GDF‐15 compared with placebo; however, GDF‐15 did not mediate the protective effect of canagliflozin on cardiovascular, HF, or kidney outcomes. Conclusions In patients with type 2 diabetes at high cardiovascular risk, higher GDF‐15 levels were associated with a higher risk of cardiovascular, HF, and kidney outcomes. Canagliflozin modestly lowered GDF‐15, but GDF‐15 reduction did not mediate the protective effect of canagliflozin.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Richard E. Pratley ◽  
◽  
Mansoor Husain ◽  
Ildiko Lingvay ◽  
Thomas R. Pieber ◽  
...  

Abstract Background Heart failure (HF) is a common cardiovascular complication of type 2 diabetes (T2D). This secondary analysis investigated baseline factors and treatment differences associated with risk of hospitalization for HF (hHF), and the possible association between severe hypoglycemia and hHF. Methods DEVOTE was a treat-to-target, double-blind cardiovascular outcomes trial in patients (n = 7637) with T2D and high cardiovascular risk randomized to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). The main endpoint of this secondary analysis was time to first hHF (standardized MedDRA Query definition). Severe hypoglycemia was adjudicated (American Diabetes Association definition). The main endpoint and the temporal association between severe hypoglycemia and hHF were analyzed with a Cox proportional hazards regression model. Predictors of time to first hHF were identified using baseline variables. Results Overall, 372 (4.9%) patients experienced hHF (550 events). There was no significant difference in the risk of hHF between treatments (hazard ratio [HR] 0.88 [0.72;1.08]95% CI, p = 0.227). Prior HF (HR 4.89 [3.90;6.14]95% CI, p ≤ 0.0001) was the strongest predictor of future hHF events. The risk of hHF significantly increased after (HR 2.2), and within a week after (HR 11.1), experiencing a severe hypoglycemic episode compared with before an episode. Conclusions In patients with T2D and high cardiovascular risk there were no treatment differences in terms of hHF. Prior HF was the strongest predictor of future hHF events, and there was an association between severe hypoglycemia and subsequent hHF. Further research should evaluate whether the risk of hHF can be modified by treatments aimed at reducing hypoglycemia. Trial Registration NCT01959529


2016 ◽  
Vol 37 (19) ◽  
pp. 1526-1534 ◽  
Author(s):  
David Fitchett ◽  
Bernard Zinman ◽  
Christoph Wanner ◽  
John M. Lachin ◽  
Stefan Hantel ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Siyao He ◽  
Xin Qian ◽  
Yanyan Chen ◽  
Xiaoxia Shen ◽  
Bo Zhang ◽  
...  

Background. To assess the association of metformin monotherapy with the risk of all-cause deaths and cardiovascular deaths and events in type 2 diabetes patients in real clinical practice. Methods. This retrospective, observational study comprised patients with type 2 diabetes initially treated with metformin or nonmetformin monotherapy over 2011-2016. Data were extracted from the National Healthcare Big Data database in Fuzhou, China. Propensity score matching (PSM) was performed, matching each patient on metformin to one on nonmetformin in terms of a set of covariates. The primary endpoint was all-cause death, and secondary endpoints were cardiovascular death, heart failure, and heart failure hospitalization. Covariate-adjusted associations of metformin use with all the endpoints were assessed by Cox proportional hazards models. Results. Among 24,099 patients, 5491 were initially treated with metformin and 18,608 with nonmetformin. PSM yielded 5482 patients in each cohort. During a median follow-up of 2.02 years, we observed 110 and 211 deaths in the metformin and nonmetformin groups, respectively. Metformin was significantly associated with reduced risk of all-cause death (adjusted hazard ratio (aHR) 0.52, 95% confidence interval (CI) 0.39-0.69), cardiovascular death (aHR 0.63, 95% CI 0.43-0.91), and heart failure (aHR 0.61, 95% CI 0.52-0.73), whereas the reduced risk in heart failure hospitalization was not statistically significant (aHR 0.70, 95% CI 0.47-1.02). Conclusions. In this analysis of electronic health record data from a large database in China, metformin as first-line monotherapy greatly reduced the risk of all-cause death, cardiovascular death, and heart failure in diabetes patients as compared with nonmetformin medications.


2021 ◽  
Vol 9 (1) ◽  
pp. e002408
Author(s):  
João Pedro Ferreira ◽  
Diana Ferrao ◽  
Patrick Rossignol ◽  
Faiez Zannad ◽  
Abhinav Sharma ◽  
...  

IntroductionPatients with type 2 diabetes (T2D) have an increased risk of worsening kidney function (WKF) over time compared with patients without diabetes. Data evaluating the inter-relation between WKF, cardiovascular risk, and clinical events are scarce. We aim to study the association of WKF with subsequent cardiovascular events and the probabilities of transition from WKF to hospitalization or death according to patients’ risk. We have used a large population of patients with T2D and a high cardiovascular risk enrolled in the Action to Control Cardiovascular Risk in Diabetes Study.Research design and methodsTime-updated, joint, and multistate modeling were used. WKF was defined as an estimated glomerular filtration rate (eGFR) decline greater than 40% from baseline. A total of 10 251 patients were included, of whom 1213 (11.8%) presented WKF over a median (percentile25–75) follow-up time of 5.0 (4.1–5.7) years.ResultsPatients who experienced WKF were slightly older, more frequently women, and had longer diabetes duration. Patients experiencing WKF, regardless of baseline kidney function, had a higher risk of subsequent cardiovascular events, including the composite of cardiovascular death or hospitalization for heart failure (HHF), with ≈2-fold higher risk. Joint modeling showed that renal function deterioration frequently occurs even among patients who did not experience a cardiovascular event. In multistate models, patients with a medium-high cardiovascular risk (compared with those with a low cardiovascular risk) are at higher risk of HHF or cardiovascular death first (HR=4.76, 95% CI 3.63 to 6.23) than of WKF first (HR=1.37, 95% CI 1.21 to 1.56); remarkably, the risk of cardiovascular death or HHF is highest after a WKF event (HR=6.20, 95% CI 2.71 to 14.8).ConclusionsIn patients with T2D and a high cardiovascular risk, WKF occurs in more than 10% of patients and is independently associated with risk of subsequent cardiovascular events, irrespective of baseline eGFR. Preventing serious WKF and the transition from WKF to HHF or cardiovascular death is an important objective of future trials.Trial registration numberNCT00000620.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Basilio Pintaudi ◽  
Alessia Scatena ◽  
Gabriella Piscitelli ◽  
Vera Frison ◽  
Salvatore Corrao ◽  
...  

Abstract Background The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. Results Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. Conclusions A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.


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