for the Cardiovascular Clinician Shaun Goodman Empagliflozin and - PowerPoint PPT Presentation

Diabetes for the Cardiovascular Clinician Shaun Goodman

Empagliflozin and CV Outcomes 7,020 pts with T2DM (A1C 7-10%; mean 8%) and CVD (CAD 1 [76% incl. Prior MI/UA >2 months prior], stroke [23%], PAD [21%]) with eGFR ≥30 mL/min/1.73m 2 CV Death/MI/Stroke CV Death/MI/Stroke Empagliflozin 10 mg HR 0.85 (0.72, 1.01) 12.1% p=0.07 HR 0.86 (0.74, 0.99) Empagliflozin 25 mg * p=0.04 HR 0.86 (0.73, 1.02) 10.5% p=0.09 Median duration 3.1 yrs NNT = 63 *10 or 25 mg PO daily For 3 years 1 Prior MI ~47; MVD ~47%; HF ~10%; CABG ~25% Zinman et al N Engl J Med 2015;373:2117-28

Liraglutide and CV Outcomes 9,340 pts ≥50 yrs with T2DM (A1C ≥7%; mean 8.7%) + CVD (CHD [incl. MI>14 days] 1, CeVD, PAD, NYHA II- III HF 1 ) or CKD (eGFR <60 ml/min: 25%) or ≥60 yrs + ≥CVD risk factor (18%) CV Death/MI/Stroke CV Death All-Cause Death: 8.2% vs. 9.6% HR 0.85 (0.74, 0.97) 14.9% p=0.02 13.0% * NNT = 66 NNT = 98 For 3 years For 3 years 6.0% Median duration 3.8 yrs 4.7% *1.8 mg SC daily 1 Prior MI ~31%; HF ~14% Marso et al N Engl J Med 2016;375:311-22

Semaglutide and CV Outcomes 3,297 pts ≥50 yrs with T2DM (A1C ≥7%; mean 8.7%) + CVD (IHD 61% [incl. MI>90 days] 1, CeVD, PAD, NYHA II-III HF 1 ) or CKD (eGFR <60 ml/min: 25%) or ≥60 yrs + ≥CVD risk factor (17%) CV Death/MI/Stroke Primary + Components 8.9% 6.6% NNT = 45 For 2 years * Median duration 2.1 yrs *0.25 mg → 0.5-1 mg SC once weekly Selected Secondary All-Cause Death: 3.8% vs. 3.6%; p=0.79 HF Hospitalization: 3.6% vs. 3.3%; p=0.57 Revascularization: 5.0% vs. 7.6%; p=0.003 1 Prior MI ~33%; HF ~24% Marso et al N Engl J Med 2016;375:1834-44

Canagliflozin and CV Outcomes 10,142 pts with T2DM (A1C 7- 10.5%; mean 8.2%) and either ≥30 yrs with symptomatic ASCVD (66%; CAD 1 [56% incl. Prior MI/UA >3 months prior], CeVD [19%], PAD [21%]) or ≥50 yrs with ≥2 CVD risk factors (34%) and eGFR ≥30 mL/min/1.73m 2 Primary + Components CV Death/MI/Stroke * NNT = 44 For 5 years Median duration 3.6 yrs *100 or 300 mg PO daily Selected Secondary All-Cause Death: 17.3 vs. 19.5; HR 0.87 (0.74, 1.01) HF Hospitalization: 5.5 vs. 8.7; HR 0.67 (0.52, 0.87) per 1000 patient-yr 1 Prior MI ~44; UA~11%; HF ~18%; PCI/CABG ~54% Neal et al N Engl J Med 2017;376:644-57

Dapagliflozin Effect on CardiovascuLAR Events Pts ≥40 yrs with CVD 1 (6,971 [41%]) or multiple risk factors (10,189 [59%] ♂≥55 or ♀≥60 yrs with dyslipidemia, ↑BP or smoking) with T2DM (A1C 6.5-12%; mean 8.3%) and eGFR ≥60 mL/min/1.73m 2 CV Death or HF Hospitalization CV Death/MI/Ischemic Stroke 5.8% 9.4% 4.9% 8.8% * Median duration 4.2 yrs *10 mg PO daily 1 51% prior MI, 52% PCI, 24% CABG, PAD 15% Wiviott et al N Engl J Med 2019;380:347-57

SGLT2 Inhibitors in Type 2 Diabetes Patients with and without Established CV Disease (CVD) Major Adverse CV Events (MACE) Hospitali- zation for Heart Failure (HF) and CV Death Zelniker et al Lancet 2019;393:31-39

SGLT2 Inhibitors in Type 2 Diabetes Patients with and without Prior HF and Established CV Disease (CVD) Hospitali- zation for Heart Failure (HF) and CV Death Composite of Renal worsening, end-stage renal disease, or renal death Zelniker et al Lancet 2019;393:31-39

GLP-1 Receptor Agonists and CV Outcomes 33,457 patients with T2DM from the ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide) trials Bethel et al Lancet Diabetes Endocrinol 2018;6:105-13

GLP-1 Receptor Agonists and CV Outcomes 33,457 patients with T2DM from the ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide) trials HF Hospitalization *Within-trial difference in all-cause mortality in EXSCEL not regarded as significant on the basis of the hierarchical statistical testing plan Bethel et al Lancet Diabetes Endocrinol 2018;6:105-13

Choice of Blood Glucose-Lowering Therapy in T2DM Patients with CVD Not at A1C Target Adapted from Lipscombe et al for the Diabetes Canada Clinical Practice Guidelines Expert Committee Can J Diabetes 2018;42:S88-103