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

Diabetes for the Cardiovascular Clinician

Shaun Goodman

Zinman et al N Engl J Med 2015;373:2117-28

Empagliflozin and CV Outcomes

CV Death/MI/Stroke

Empagliflozin 10 mg HR 0.85 (0.72, 1.01) p=0.07 Empagliflozin 25 mg HR 0.86 (0.73, 1.02) p=0.09

7,020 pts with T2DM (A1C 7-10%; mean 8%) and CVD (CAD1 [76% incl. Prior MI/UA >2 months prior], stroke [23%], PAD [21%]) with eGFR ≥30 mL/min/1.73m2

1Prior MI ~47; MVD ~47%; HF ~10%; CABG ~25%

CV Death/MI/Stroke

Median duration 3.1 yrs HR 0.86 (0.74, 0.99) p=0.04

10.5% 12.1%

*

*10 or 25 mg PO daily

NNT = 63 For 3 years

Marso et al N Engl J Med 2016;375:311-22

Liraglutide and CV Outcomes

CV Death/MI/Stroke

9,340 pts ≥50 yrs with T2DM (A1C ≥7%; mean 8.7%) + CVD (CHD [incl. MI>14 days]1, CeVD, PAD, NYHA II- III HF1) or CKD (eGFR<60 ml/min: 25%) or ≥60 yrs + ≥CVD risk factor (18%)

1Prior MI ~31%; HF ~14%

Median duration 3.8 yrs

13.0% 14.9%

CV Death

4.7% 6.0%

All-Cause Death: 8.2% vs. 9.6% HR 0.85 (0.74, 0.97) p=0.02

NNT = 98 For 3 years

*1.8 mg SC daily

*

NNT = 66 For 3 years

Marso et al N Engl J Med 2016;375:1834-44

Semaglutide and CV Outcomes

CV Death/MI/Stroke

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 HF1) or CKD (eGFR<60 ml/min: 25%) or ≥60 yrs + ≥CVD risk factor (17%)

1Prior MI ~33%; HF ~24%

Median duration 2.1 yrs

6.6% 8.9%

Primary + Components

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

Selected Secondary

*0.25 mg → 0.5-1 mg SC once weekly

*

NNT = 45 For 2 years

Neal et al N Engl J Med 2017;376:644-57

Canagliflozin and CV Outcomes

10,142 pts with T2DM (A1C 7-10.5%; mean 8.2%) and either ≥30 yrs with symptomatic ASCVD (66%; CAD1 [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/1.73m2

1Prior MI ~44; UA~11%; HF ~18%; PCI/CABG ~54%

CV Death/MI/Stroke

Median duration 3.6 yrs

*100 or 300 mg PO daily

NNT = 44 For 5 years

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

Selected Secondary Primary + Components

*

Wiviott et al N Engl J Med 2019;380:347-57

Pts ≥40 yrs with CVD1 (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/1.73m2

151% prior MI, 52% PCI, 24% CABG, PAD 15%

CV Death/MI/Ischemic Stroke

Dapagliflozin Effect on CardiovascuLAR Events

8.8% 9.4%

CV Death or HF Hospitalization

*10 mg PO daily

*

Median duration 4.2 yrs

4.9% 5.8%

SGLT2 Inhibitors in Type 2 Diabetes Patients with and without Established CV Disease (CVD)

Zelniker et al Lancet 2019;393:31-39

Major Adverse CV Events (MACE) Hospitali- zation for Heart Failure (HF) and CV Death

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

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

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

*Within-trial difference in all-cause mortality in EXSCEL not regarded as significant on the basis of the hierarchical statistical testing plan

HF Hospitalization

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