Subodh Verma1,2,3,4, C David Mazer5,6,7, Andrew T Yan8,9,4, Tamique Mason1,3, Vinay Garg1,3,9, Hwee Teoh1,10, Fei Zuo11, Adrian Quan1, Michael E Farkouh9,4,12, David H Fitchett8,9, Shaun G Goodman8,9,13,14, Ronald M Goldenberg15, Mohammed Al-Omran16,2,3, Richard E Gilbert10,9, Deepak L Bhatt17, Lawrence A Leiter10,9,18, Peter Jüni11,9,19, Bernard Zinman9,20, Kim A Connelly8,7,9,4. 1. Division of Cardiac Surgery (S.V., T.M, V.G., H.T., A.Q.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 2. Department of Surgery (S.V., M.A.O.), University of Toronto, Ontario, Canada. 3. Department of Pharmacology and Toxicology (S.V., T.M., V.G., M.A.O.), University of Toronto, Ontario, Canada. 4. Heart and Stroke Richard Lewar Centre (S.V., A.T.Y., M.E.F., K.A.C.), University of Toronto, Ontario, Canada. 5. Department of Anesthesia (C.D.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 6. Department of Anesthesia (C.D.M.), University of Toronto, Ontario, Canada. 7. Department of Physiology (C.D.M., K.A.C.), University of Toronto, Ontario, Canada. 8. Division of Cardiology (A.T.Y., D.H.F., S.G.G., K.A.C.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 9. Department of Medicine (A.T.Y., V.G., M.E.F., D.H.F., S.G.G., R.E.G., L.A.L., P.J., B.Z., K.A.C.), University of Toronto, Ontario, Canada. 10. Division of Endocrinology and Metabolism (H.T., R.E.G., L.A.L.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 11. Applied Health Research Centre (F.Z., P.J.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 12. Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital/Mount Sinai Hospital, Ontario, Canada (M.E.F.). 13. Canadian Heart Research Centre, Toronto, Ontario (S.G.G.). 14. Canadian Virtual Coordinating Centre for Global Collaborative Cardiovascular Research Centre, University of Alberta, Edmonton (S.G.G.). 15. LMC Diabetes & Endocrinology, Concord, Ontario, Canada (R.M.G.). 16. Division of Vascular Surgery (M.A.O.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 17. Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, MA (D.L.B.). 18. Department of Nutritional Sciences (L.A.L.), University of Toronto, Ontario, Canada. 19. Institute of Health Policy, Management, and Evaluation (P.J.), University of Toronto, Ontario, Canada. 20. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (B.Z.).
Abstract
BACKGROUND:SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease. METHODS:Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide). RESULTS: Among the 97 participants (90 men [93%], mean [standard deviation] age 62.8 [9.0] years, type 2 diabetes mellitus duration 11.0 [8.2] years, estimated glomerular filtration rate 88.4 [16.9] mL/min/1.73m2, LV mass indexed to body surface area 60.7 [11.9] g/m2), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2; 95% CI, -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg; 95% CI, -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003). CONCLUSIONS: Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition withempagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02998970.
RCT Entities:
BACKGROUND:SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease. METHODS: Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide). RESULTS: Among the 97 participants (90 men [93%], mean [standard deviation] age 62.8 [9.0] years, type 2 diabetes mellitus duration 11.0 [8.2] years, estimated glomerular filtration rate 88.4 [16.9] mL/min/1.73m2, LV mass indexed to body surface area 60.7 [11.9] g/m2), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2; 95% CI, -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg; 95% CI, -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003). CONCLUSIONS: Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02998970.
Authors: Nick S R Lan; Bu B Yeap; P Gerry Fegan; Gillian Green; James M Rankin; Girish Dwivedi Journal: Int J Cardiovasc Imaging Date: 2020-09-21 Impact factor: 2.357
Authors: Mark C Petrie; Subodh Verma; Kieran F Docherty; Silvio E Inzucchi; Inder Anand; Jan Belohlávek; Michael Böhm; Chern-En Chiang; Vijay K Chopra; Rudolf A de Boer; Akshay S Desai; Mirta Diez; Jaroslaw Drozdz; Andre Dukát; Junbo Ge; Jonathan Howlett; Tzvetana Katova; Masafumi Kitakaze; Charlotta E A Ljungman; Béla Merkely; Jose C Nicolau; Eileen O'Meara; Pham Nguyen Vinh; Morten Schou; Sergey Tereshchenko; Lars Køber; Mikhail N Kosiborod; Anna Maria Langkilde; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon; Per Johanson; Peter J Greasley; David Boulton; Olof Bengtsson; Pardeep S Jhund; John J V McMurray Journal: JAMA Date: 2020-04-14 Impact factor: 56.272