The effect of empagliflozin on the total burden of cardiovascular and hospitalization events in the Asian and non‐Asian populations of the EMPA‐REG OUTCOME trial of patients with type 2 diabetes and cardiovascular disease

Abstract Background Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10 mg or 25 mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR = 1.73 (95% CI 1.01–2.98), heart failure hospitalization: HR = 2.64 (95% CI 1.22, 5.72), and new or worsening nephropathy: HR = 3.11 (95% CI 2.17–4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS. Conclusions A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS. Trial registration Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT 01131676

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P6270Empagliflozin reduces the total burden of first and recurrent hospitalisations in patients with type 2 diabetes and established cardiovascular disease

European Heart Journal ◽

10.1093/eurheartj/ehz746.0869 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

D McGuire ◽

B Zinman ◽

S E Inzucchi ◽

S D Anker ◽

C Wanner ◽

...

Keyword(s):

Type 2 Diabetes ◽

Recurrent Events ◽

Negative Binomial ◽

Cox Regression ◽

Standard Of Care ◽

History Of ◽

Outcome Trial ◽

Cv Disease ◽

Total Burden

Abstract Background and aims The EMPA-REG OUTCOME trial included patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular (CV) disease. Empagliflozin reduced the risk of 3-point major adverse CV events (MACE; composite of CV death, myocardial infarction [MI], or stroke) by 14%, CV death by 38% and hospitalisation for heart failure (HF) by 35% vs placebo in analyses of time to first event. We assessed the effect of empagliflozin on all-cause hospitalisation in post-hoc analyses of all (first and recurrent) events. Materials and methods Patients were randomised to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo in addition to standard of care. We assessed the effects of empagliflozin pooled vs placebo on first event of all-cause hospitalisation using Cox regression and all (first and recurrent) events of all-cause hospitalisation using a negative binomial model. Results A total of 7020 patients were treated (4687 empagliflozin; 2333 placebo, mean [SD] age 63 [9] years, 71% male, 47% with history of MI, 23% with history of stroke, 10% with HF). In this analysis, 1725/4687 (36.8%) empagliflozin patients and 925/2333 (39.6%) placebo patients experienced an event leading to hospitalisation. The adjusted hazard ratio (HR; 95% CI) vs placebo for first all-cause hospitalisation using the Cox regression model was 0.89 (0.82, 0.96; p=0.0033; Figure); In analyses of all (first and recurrent) hospitalisation events, there were 3168 events in the empagliflozin group and 1863 in the placebo group. The adjusted event rate ratio (95% CI) vs placebo was 0.83 (0.76, 0.91; p<0.0001; Figure). Conclusion In the EMPA-REG OUTCOME trial, risk reductions with empagliflozin were seen in both first and all hospitalisation events and were numerically more favourable in analyses of all events vs analyses of first events. These analyses expand on the favourable CV effects of empagliflozin by also showing a reduction in the total burden of hospitalisation events in patients with T2D and established CV disease. Acknowledgement/Funding Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance

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Metabolic Syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: A post hoc analyses of the EMPA-REG OUTCOME trial

10.21203/rs.3.rs-64853/v2 ◽

2020 ◽

Author(s):

João Pedro Ferreira ◽

Subodh Verma ◽

David Fitchett ◽

Anne Pernille Ofstad ◽

Sabine Lauer ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

World Health ◽

Atherosclerotic Cardiovascular Disease ◽

Mixed Effect ◽

Renal Outcomes ◽

Outcome Trial

Abstract Background: Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods: A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10mg or 25mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results: MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR=1.73 (95%CI=1.01-2.98), heart failure hospitalization: HR=2.64 (95%CI=1.22, 5.72), and new or worsening nephropathy: HR=3.11 (95%CI=2.17-4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS.Conclusions: A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS.

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Effect of empagliflozin when added to insulin in patients with type 2 diabetes and established cardiovascular disease: Results from the EMPA-REG OUTCOME trial

Diabetologie und Stoffwechsel ◽

10.1055/s-0037-1601614 ◽

2017 ◽

Vol 12 (S 01) ◽

pp. S1-S84

Author(s):

D Jurišić-Eržen ◽

OE Johansen ◽

J George ◽

M Mattheus ◽

B Zinman ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Outcome Trial

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Metabolic Syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: A post hoc analyses of the EMPA-REG OUTCOME trial

10.21203/rs.3.rs-64853/v1 ◽

2020 ◽

Author(s):

João Pedro Ferreira ◽

Subodh Verma ◽

David Fitchett ◽

Anne Pernille Ofstad ◽

Sabine Lauer ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

World Health ◽

Atherosclerotic Cardiovascular Disease ◽

Mixed Effect ◽

Renal Outcomes ◽

Outcome Trial

Abstract Background Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10 mg or 25 mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR = 1.73 (95%CI = 1.01–2.98), heart failure hospitalization: HR = 2.64 (95%CI = 1.22, 5.72), and new or worsening nephropathy: HR = 3.11 (95%CI = 2.17–4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS. Conclusions A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT 01131676.

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