Effects of empagliflozin on myocardial flow reserve in patients with type 2 diabetes mellitus: The simple trial
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- Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial
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BACKGROUND: Sodium– glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk. METHODS AND RESULTS: We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add-on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium-82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate-pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08– 2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, −0.18 to 0.21) or placebo groups: 0.06 (95% CI, −0.15 to 0.27), with no treatment effect −0.05 (95% CI, −0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium-82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A1c by 0.76% (95% CI, 1.0– 0.5; P<0.001) and increased hematocrit by 1.69% (95% CI, 0.7– 2.6; P<0.001). CONCLUSIONS: Empagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short-term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials. REGISTRATION: URL: https://clinicaltrialsregister.eu/; Unique identifier: 2016-003743-10.
|Tidsskrift||Journal of the American Heart Association|
|Status||Udgivet - 2021|
This work is supported by the Department of Internal Medicine at Herlev Hospital; the Research Council of Herlev Hospital; The Danish Heart Foundation, grant number 16-R107-A6697; The Hartmann Foundation; The Toyota Foundation and by a Steno Collaborative Grant 2018.
Dr Kistorp has served on scientific advisory panels and received speaker fees from Boehringer Ingelheim, Merck Shape and Dome, Astra Zeneca, Amgen, Novartis, Novo Nordisk, and Shire. Dr Rossing has received consultancy and/or speaking fees (to his institution) from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk, and Sanofi Aventis; and research grants from AstraZeneca and Novo Nordisk. Dr Inzucchi has received consultancy and speaking fees from Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Merck, and Esperion. Dr Wolsk has received speaker fees from Orion Pharma, Novartis Healthcare, Boehringer-Ingelheim, and Merck. The remaining authors have no disclosures to report.
© 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.