Jacob A Udell1, Deepak L Bhatt2, Eugene Braunwald2, Matthew A Cavender2, Ofri Mosenzon3, Ph Gabriel Steg4, Jaime A Davidson5, Jose C Nicolau6, Ramon Corbalan7, Boaz Hirshberg8, Robert Frederich9, KyungAh Im2, Amarachi A Umez-Eronini2, Ping He2, Darren K McGuire10, Lawrence A Leiter11, Itamar Raz3, Benjamin M Scirica12. 1. Cardiovascular Division, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada. 2. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 3. Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel. 4. Département Hospitalo-Universitaire-Fibrosis Inflammation Remodelling, INSERM U-1148, Université Paris-Diderot, and Hôpital Bichat, AP-HP, Paris, France Imperial College, Royal Brompton Hospital, London, U.K. 5. Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 6. Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. 7. Cardiovascular Division, Pontificia Universidad Católica de Chile, Santiago, Chile. 8. AstraZeneca Research and Development, Wilmington, DE. 9. Bristol-Myers Squibb, Princeton, NJ. 10. Division of Cardiovascular Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 11. Division of Endocrinology and Metabolism, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 12. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA bscirica@partners.org.
Abstract
OBJECTIVE: The glycemic management of patients with type 2 diabetes mellitus (T2DM) and renal impairment is challenging, with few treatment options. We investigated the effect of saxagliptin in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial according to baseline renal function. RESEARCH DESIGN AND METHODS: Patients with T2DM at risk for cardiovascular events were stratified as having normal or mildly impaired renal function (estimated glomerular filtration rate [eGFR] >50 mL/min/1.73 m(2); n = 13,916), moderate renal impairment (eGFR 30-50 mL/min/1.73 m(2); n = 2,240), or severe renal impairment (eGFR <30 mL/min/1.73 m(2); n = 336) and randomized to receive saxagliptin or placebo. The primary end point was cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS: After a median duration of 2 years, saxagliptin neither increased nor decreased the risk of the primary and secondary composite end points compared with placebo, irrespective of renal function (all P for interactions ≥ 0.19). Overall, the risk of hospitalization for heart failure among the three eGFR groups of patients was 2.2% (referent), 7.4% (adjusted hazard ratio [HR] 2.38 [95% CI 1.95-2.91], P < 0.001), and 13.0% (adjusted HR 4.59 [95% CI 3.28-6.28], P < 0.001), respectively. The relative risk of hospitalization for heart failure with saxagliptin was similar (P for interaction = 0.43) in patients with eGFR >50 mL/min/1.73 m(2) (HR 1.23 [95% CI 0.99-1.55]), eGFR 30-50 mL/min/1.73 m(2) (HR 1.46 [95% CI 1.07-2.00]), and in patients with eGFR <30 (HR 0.94 [95% CI 0.52-1.71]). Patients with renal impairment achieved reductions in microalbuminuria with saxagliptin (P = 0.041) that were similar to those of the overall trial population. CONCLUSIONS:Saxagliptin did not affect the risk of ischemic cardiovascular events, increased the risk of heart failure hospitalization, and reduced progressive albuminuria, irrespective of baseline renal function.
RCT Entities:
OBJECTIVE: The glycemic management of patients with type 2 diabetes mellitus (T2DM) and renal impairment is challenging, with few treatment options. We investigated the effect of saxagliptin in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial according to baseline renal function. RESEARCH DESIGN AND METHODS: Patients with T2DM at risk for cardiovascular events were stratified as having normal or mildly impaired renal function (estimated glomerular filtration rate [eGFR] >50 mL/min/1.73 m(2); n = 13,916), moderate renal impairment (eGFR 30-50 mL/min/1.73 m(2); n = 2,240), or severe renal impairment (eGFR <30 mL/min/1.73 m(2); n = 336) and randomized to receive saxagliptin or placebo. The primary end point was cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS: After a median duration of 2 years, saxagliptin neither increased nor decreased the risk of the primary and secondary composite end points compared with placebo, irrespective of renal function (all P for interactions ≥ 0.19). Overall, the risk of hospitalization for heart failure among the three eGFR groups of patients was 2.2% (referent), 7.4% (adjusted hazard ratio [HR] 2.38 [95% CI 1.95-2.91], P < 0.001), and 13.0% (adjusted HR 4.59 [95% CI 3.28-6.28], P < 0.001), respectively. The relative risk of hospitalization for heart failure with saxagliptin was similar (P for interaction = 0.43) in patients with eGFR >50 mL/min/1.73 m(2) (HR 1.23 [95% CI 0.99-1.55]), eGFR 30-50 mL/min/1.73 m(2) (HR 1.46 [95% CI 1.07-2.00]), and in patients with eGFR <30 (HR 0.94 [95% CI 0.52-1.71]). Patients with renal impairment achieved reductions in microalbuminuria with saxagliptin (P = 0.041) that were similar to those of the overall trial population. CONCLUSIONS:Saxagliptin did not affect the risk of ischemic cardiovascular events, increased the risk of heart failure hospitalization, and reduced progressive albuminuria, irrespective of baseline renal function.
Authors: Priyesh A Patel; Li Liang; Prateeti Khazanie; Bradley G Hammill; Gregg C Fonarow; Clyde W Yancy; Deepak L Bhatt; Lesley H Curtis; Adrian F Hernandez Journal: Circ Heart Fail Date: 2016-07 Impact factor: 8.790
Authors: Benjamin M Scirica; Ofri Mosenzon; Deepak L Bhatt; Jacob A Udell; Ph Gabriel Steg; Darren K McGuire; KyungAh Im; Estella Kanevsky; Christina Stahre; Mikaela Sjöstrand; Itamar Raz; Eugene Braunwald Journal: JAMA Cardiol Date: 2018-02-01 Impact factor: 14.676