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The Management of Patients with Heart Failure and Diabetes
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
The EMPA-REG OUTCOME trial was the first study to provide evidence of improved HF outcomes with a drug (empagliflozin), the target population of which was diabetics. Empagliflozin belongs to the SGLT-2 inhibitor family. In the kidneys, SGLT-2 serves as a sodium-glucose cotransporter and reabsorbs about 90% of the glucose, while promoting natriuresis. SGLT-2 inhibitors block this channel, enhancing glucosuria. Worsening hyperglycemia augments their function, whereas lower glucose level diminishes their efficacy, decreasing the risk of hypoglycemia with SGLT-2 inhibitors alone. However, the risk of hypoglycemia increases when SGLT-2 inhibitors are combined with insulin or insulin secretagogues, such as sulfonylureas.33
Diabetes mellitus and cardiovascular disease in the elderly
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Because this class of drugs is new, long-term safety data is scant. In spite of this there is promise that this class can result in beneficial cardiovascular and renal outcomes. The Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA-REG OUTCOME) reported in 2015 demonstrated reduction in cardiovascular and all-cause mortality and hospitalization for heart failure with empagliflozin compared to placebo in patients with type 2 diabetes and cardiovascular disease (146,147). This same trial demonstrated the empagliflozin reduced the incidence of clinically relevant increase in serum creatinine and the initiation of renal replacement therapy. Cardiovascular outcomes trials for canagliflozin and dapagliflozin are ongoing.
Pharmacological treatment options for heart failure with reduced ejection fraction: A 2022 update
Published in Expert Opinion on Pharmacotherapy, 2022
Kristian Hellenkamp, Kathleen Nolte, Stephan von Haehling
SGLT2 inhibitors were originally intended for the management and therapy of type 2 diabetes mellitus. Indeed, the ESC HF guidelines list more SGLTS2 inhibitors (canagliflozin, ertugliflozin, and sotagliflozin) than dapagliflozin and empagliflozin for the treatment of diabetes mellitus in patients at risk of cardiovascular events in order to prevent hospitalizations for worsening HF[4]. Only dapagliflozin and empagliflozin are recommended to be used in all patients with manifest HF, irrespective of the presence of diabetes. Moreover, different trials have shown a clear benefit in the management of HF. The EMPA-REG OUTCOME trial proved reduced HF hospitalizations and cardiovascular deaths in patients with type 2 diabetes and high cardiovascular risk, when they were treated with empagliflozin added to standard care, in contrast to placebo. EMPA-REG OUTCOME randomly assigned patients with type 2 diabetes to receive 10 mg, 25 mg of empagliflozin or placebo once daily. A total of 7,020 were treated and the trial was very positive in that it reduced the primary outcome of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. These benefits were consistent in patients with and without HF at baseline. However, the EMPA-REG OUTCOME trial was not a dedicated HF trial, and the history of HF was based on medical record review rather than on physical, laboratory, or imaging results[25].
Growing role of SGLT2i in heart failure: evidence from clinical trials
Published in Expert Review of Clinical Pharmacology, 2022
Ajay Varadhan, Katarina Stephan, Rahul Gupta, Apurva V. Vyas, Purva Ranchal, Wilbert S. Aronow, Nael Hawwa, Gregg M. Lanier
The Study of Heart and Kidney Protection With Empagliflozin (EMPA-Kidney) is an ongoing clinical trial that addresses the unmet clinical need for further evidence in reducing the risk of CV and kidney disease progression in patients with CKD irrespective of whether they have diabetes. 5,000 patients (≥1/3 with DM and ≥1/3 without DM) are currently enrolled and receive empagliflozin at 10 mg/d compared to the placebo group [55]. The primary outcome of the trial is the rate of a sustained ≥40% decline in eGFR, end-stage kidney disease or death from renal or CV causes. Secondary outcomes include CV death or hospitalization for heart failure, all-cause hospitalization and all-cause mortality; results are expected at the end of this trial in 2022. EMPA-Kidney is uniquely designed to expand existing evidence for interventions for patients with forms of kidney disease across the spectrum, including inclusion criteria for patients with T1DM and patients with eGFR between 20 and < 45 min/min/1.73 m2 who have little or no albuminuria/proteinuria [59].
Efficient agent degradation within skin is important for decontamination of percutaneously exposed VX
Published in Cutaneous and Ocular Toxicology, 2021
Lina Thors, Elisabeth Wigenstam, Johanna Qvarnström, Anders Bucht
EMPA is a hydrolysis product of VX, and is the main degradation product of VX in RSDL16,19. In the 1 µl sample exposed on skin, approximately 5% consisted of EMPA, which was also analyzed in individual tapes and in the receptor solution. Differently from VX, larger amounts of EMPA were recovered in the tapes after 1 h than in the remaining skin but similarly to VX, the amount in the receptor solution was very small also for EMPA. The recovery of EMPA primarily on the skin and in the stratum corneum likely reflects the higher hydrophilicity of EMPA compared to VX (logP −0.85 ± 0.62 and 2.05 ± 0.36 for EMPA and VX, respectively), resulting in a lower skin permeability43,44. All three decontamination protocols significantly decreased the EMPA amount in the tapes representing the main part of stratum corneum. RSDL and TRSDL also significantly reduced the agent amount in receptor solution samples, while the amounts following soapy water decontamination were unaffected compared to the control without decontamination. This indicates that the risk for a “wash-in” effect is lower for the hydrophilic EMPA than for the more lipophilic VX. Decontamination by RSDL could potentially result in increased amounts of EMPA due to degradation of VX, however, no such effect was observed during the relatively short 1 h experimental time. No information is available regarding the acute toxicity of EMPA45. However, it can be used to identify the exposure of VX in both serum and urine samples from victims46,47.