and prevention in cardiorenal disease John Deanfield, MD London, - - PowerPoint PPT Presentation

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Importance of protection and prevention in cardiorenal disease John Deanfield, MD London, United Kingdom June 15, 2019 - Budapest, Hungary Protection and Prevention in Diabetic Cardio-renal Disease Professor John Deanfield - University

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Importance of protection and prevention in cardiorenal disease

John Deanfield, MD London, United Kingdom

June 15, 2019 - Budapest, Hungary

SLIDE 2

Protection and Prevention in Diabetic Cardio-renal Disease

Professor John Deanfield - University College London, UK Budapest ERA EDTA - 15 June 2019

Deanfield  UCL

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CVD Challenge in Diabetes is Clear

Source: Seshasai et al, N Engl J Med 2011; 364:829-41

On average, a 50-year old with diabetes but no history of vascular disease is ~6 years younger at time of death than a counterpart without diabetes Men Women

7 6 5 4 3 2 1 40 50 60 70 80 90 Age (years) Years of life lost 7 6 5 4 3 2 1 40 50 60 70 80 90 Age (years) Vascular deaths Non-vascular deaths

Deanfield  UCL

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Need for Joint Approach…CVD and CKD Go Together!

Deanfield  UCL

“It is observable, that the hypertrophy

f the heart seems, in some degree, to

have kept pace with the advance of disease in the kidneys; for in by far the majority of cases, when the heart was increased, the hardness and contraction of the kidney bespoke the probability of long continuance of the disease.”

R Bright, 1836

Diabetes CKD CVD

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Cardio-renal Disease in Diabetes

Deanfield  UCL

Novel treatments can improve cardio-renal outcomes in patients with diabetes Prevention is important as long term exposure to risk factors drives cardio-renal disease

Never Too Late…Never Too Early…!!

Leveraged gain from early intervention on common pathways to disease Emerging early role for new drugs?

SLIDE 6

Statins
BP Lowering
Metformin
ACEi / ARB

SGLT2-i GLP1-RA

Evidence Based Cardiorenal Risk Reduction

Deanfield  UCL

SLIDE 7

Empagliflozin, CV Outcomes and Mortality in T2DM

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

Primary Outcome Death from Cardiovascular Causes Death from Any Cause Hospitalization for Heart Failure

Deanfield  UCL

SLIDE 8

Source: Marso SP et al. N Engl J Med 2016;375:311–322 Source: Marso SP et al. N Engl J Med 2016;375:1834–1844

LEADER

Time to first occurrence of CV death, non-fatal MI or non-fatal stroke

6 1 2 1 8 2 4 3 0 3 6 4 2 4 8 5 4 5 1 0 1 5 2 0

Patients with event (%)

Placebo Liraglutide HR: 0.87 (95% CI: 0.78 ; 0.97) p<0.001 for non-inferiority p=0.01 for superiority

Time from randomisation (months)

SUSTAIN 6

Semaglutide Placebo

Patients with event (%)

HR: 0.74 (95% CI: 0.58 ; 0.95) p<0.001 for non-inferiority p=0.02 for superiority

Time from randomisation (months)

GLP-1RA CV Outcome Trials

Deanfield  UCL

SLIDE 9

Source: Newman JD, et al, J Am Coll Cardiol 2018; 72(15):1856-69

Diabetes Treatment for CVD Reduction

SGLT-2 Inhibitors GLP-1R Agonists

Deanfield  UCL

SLIDE 10

Source: Newman JD, et al, J Am Coll Cardiol 2018; 72(15):1856-69

Renal Benefit from GLP-1RA and SGLT-2i

Deanfield  UCL

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9,900 individuals with T2DM and eGFR of ≥ 15mL/min; Dulaglutide v Placebo; > two thirds primary CV prevention

Source: Hertzel C Gerstein, Lancet x.doi.org/10.1016/S0140-6736(19)31150-X

Deanfield  UCL

REWIND

Cumulative (%) Time Since Randomisation (yrs)

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Exciting New Era for CVD Management in DM

Diabetologists Cardiologists Primary Care Nephrology

Deanfield  UCL

SLIDE 13

A Thought…

“Why just strive to treat a disease like Diabetes better when you could prevent it?”

Deanfield  UCL

SLIDE 14

Source: IDF Diabetes Atlas. 7th edn. 2015

2015 2040

Source Bjerregaard et al, N Engl J Med 2018;378:1302-12

Diabetes Epidemic : Risk Factors start Early!

Deanfield  UCL

SLIDE 15

The Ticking Clock:  CV Risk Before  Glucose (Nurses’ Health Study)

Source: Hu et al, Diabetes Care 2002; 25: 1129-1134

20 yr F/U of 117,629 women: n=1,508 diabetes at B/L; n=5,894 developed diabetes; n=110,227 free from diabetes

0.0 Relative risk of MI or stroke Nondiabetic throughout the study Risk of event prior to DM diagnosis Risk of event after DM diagnosis Diabetic at B/L 6.0 5.0 4.0 3.0 2.0 1.0 5.02 3.71 2.82 1.0

Deanfield  UCL

SLIDE 16

Source: Lean, M et al, Lancet 2018; 391: 541–51

Primary Care-led Weight Management For Remission

f T2DM (DiRECT)

> 10kg Weight Loss 64%Remission

Deanfield  UCL

SLIDE 17

Impact of GLP1-RA on Obesity

Source: O’Neil et al, Lancet 2018; 392: 637–49 Deanfield  UCL

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Four Weeks Of Liraglutide Inhibits Progression Of Atherosclerotic Lesions In ApoE-/- mice

Gaspari T et al. Diab Vasc Dis Res 2013;10:353‒60.

IMR

0.4 0.3 0.2 0.1 0.0

Vehicle Lira Lira + Ex-9

* IMR analysis performed in the aortic arch

Intima‒media ratio (IMR)

N=6‒10

Lesion area (%)

15 10 5

Vehicle Lira Lira + Ex-9

Oil red O staining performed in the aorta

Lipid deposition

N=13‒16

Vehicle Lira Lira + Ex-9

M M I M I

Lesion development

Haemotoxylin and eosin staining in the aortic arch

Deanfield  UCL

SLIDE 19

Semaglutide s.c. 2.4 mg once-weekly Placebo s.c. once-weekly Event driven

1225 first MACEs

Randomisation (1:1) N=17,500 patients Male or female ≥45 years of age BMI ≥27

Prior MI Prior stroke PAD

SELECT: GLP1-RA in high CVD risk Non Diabetics

Primary endpoint: Time from randomisation to first occurrence of a composite endpoint consisting of either:

CV death
Non-fatal myocardial infarction
Non-fatal stroke

Deanfield  UCL

SLIDE 20

CV RFs Drive Multiple Diseases Through Common Pathways

Obesity Stress BP Smoking Systemic Inflammation

 Ageing

Diabetes CKD CVD Cancer Cholesterol Oxidative Stress Dementia Stroke

Deanfield  UCL

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Impact of Periodontitis Treatment on Glucose Control, Vascular and Renal Function in T2DM

Source: D’Aiuto Lancet Diabetes 2018

In UK population ▪ Severe in 5-10% ▪ Mild/mod. in 40%

Deanfield  UCL

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How Early Should Prevention Start? “Poor Start in Life”

Deanfield  UCL

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Obesity at 2 yrs Predicts Status at 35 yrs...

Source: Ward et al, N Engl J Med 2017;377:2145-53 Deanfield  UCL

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Source: Twig G et al, NEJM 2016;374:2430-40

BMI During Adolescence and CV Mortality

Diabetes and Hypertension

Deanfield  UCL

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Cardio-renal Disease in Diabetes: Protection & Prevention

Deanfield  UCL

New era for treatment of cardio-renal disease Earlier management is needed to target disease in the population Emerging role for new drugs and lifestyle in pre-clinical disease

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Final Thought…

“It should be the function of medicine to have people die young as late as possible”

Ernest L. Wynder M.D

Deanfield  UCL

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