CVD: Extending the opportunities John E Deanfield, MD London, - - PowerPoint PPT Presentation

The clinical landscape for T2DM and CVD: Extending the opportunities John E Deanfield, MD

London, United Kingdom

Cardio Diabetes Master Class

February 22-23, 2019 - Barcelona, Spain

Deanfield  UCL

The Clinical Challenge

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

Deanfield  UCL

Treatment Goals in T2DM

Management should be targeted at reducing / delaying CV complications in patients with T2DM with and without clinical CVD

Not just icing on the cake!!!

PACE Dubai 2018

• Statins
• BP Lowering
• Metformin

SGLT2-i GLP1-RA

Evidence Based CV Risk Reduction

Adverse Events

p-value* Any adverse event <0.001 Serious adverse event 0.01 Severe adverse event 0.22 Nausea <0.001 Vomiting <0.001 Diarrhoea <0.001 Lipase increased† 0.43 Abdominal pain 0.03 Decreased appetite 0.01 Abdominal discomfort 0.002 Proportion of patients (%) Liraglutide Placebo

Cost-effectiveness

Deanfield  UCL

Guidelines

CVOT Impact on Clinical Guidelines

Source: American Diabetes Association. Diabetes Care 2018;41 (Suppl 1):S73–S85

ADA 2018 recommendation

In patients with type 2 diabetes and established atherosclerotic cardiovascular disease, antihyperglycemic therapy should begin with lifestyle management and metformin and subsequently incorporate an agent proven to reduce major adverse cardiovascular events and cardiovascular mortality (currently, empagliflozin and liraglutide), after considering drug-specific and patient factors (Table 8.1).

Draft ADA and EASD consensus guideline

• 1. SGLT2-i = Empagliflozin preferred, GLP-1 RA = Liraglutide preferred. Proven CVD benefit means it has label indication of reducing CVD events. Please see hierarchy of evidence in manuscript for CVD benefits for

• 5. Low dose may be better tolerated though less well studied for CVD effect; 6. Choose later generation SU with lower risk of hypoglycaemia

ASCVD predominates

If further intensification is required or patient is now unable to tolerate GLP-1 RA and/or SGLT2-i, choose agents demonstrating CV safety:

• Consider adding the other class with proven CVD benefit
• DDP-IVi if not on GLP-1 RA
• Basal insulin4
• TZD5
• SU6

If HbA1c above target GLP-1 RA with proven CVD benefits1 SGLT2-i with proven CVD benefit if eGFR adequate1-2

OR

Heart failure (HF) predominates

• Avoid TZD

Choose agents demonstrating CV safety:

• Consider adding the other class with proven CVD benefit1
• DDP-IVi (not Saxagliptin) if not on GLP-1 RA
• Basal insulin4
• SU6

If HbA1c above target SGLT2-i with evidence

• f reducing HF in CVOT

trials if eGFR adequate2-

3

GLP-1 RA with proven CVD benefit1

OR

Deanfield  UCL

Implementation

Insulin Resistance: An Inflammatory Atherothrombotic Syndrome

INSULIN RESISTANCE

Hyperglycaemia Hyperinsulinaemia Hypertension

Smoking

Fibrinogen Factor VII Factor XII PAI-1 tPA Triglyceride Cholesterol

CRP Monocytes Cytokines Adhesion Molecules

Insulin Resistance

Deanfield  UCL

How to Organize Best Care for Patients with Diabetes? Diabetologists, Cardiologists, Nephrologists, Primary Care physicians need to work together in care plan

ESC  Munich 2018

Barriers to Best Care

• Cardiologists

➢ General medicine poor ➢ Uncomfortable with Hypos ➢ Don’t like injectables!

• Diabetologists

➢ Disenfranchised by cardiologists ➢ Lack of effective CVD treatments until now ➢ Complex glucose centric guidelines

Source: INTERHEART Lancet 2004

Investing In Your Arteries!

April 19

20 40 60 Age (yrs)

Genetic Environmental

Foetus Diabetologists should be Preventative Cardiologists! Clinical Events Lots of risk in front : lots of lost opportunities behind!

Personalised Nutrition by Prediction of Glycemic Responses

Source: Zeevi Cell 2015; 163: 1079-1094 Deanfield  UCL

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: Trial Design ,Population and Endpoint

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

• CV death
• Non-fatal myocardial infarction
• Non-fatal stroke

ESC  Munich 2018

“Sick Individuals and Sick Populations”

Source: Rose, Int. J Epidemiol,1985;14:32-38

Geoffrey Rose, CBE (April 1926 – November 1993)

• Two strategies for prevention:
• The ‘high risk’ approach

seeking to protect susceptible individuals

• The ‘population’ approach

to control the underlying causes of incidence

Deanfield  UCL

The Public Health Challenge

Diabetes is a growing epidemic

http://blogs.reuters.com/data-dive/2013/11/15/the-world-diabetes-epidemic-in-charts/

1:10 people in the world will have diabetes by 2035….

CVD: It’s Not All Over!

Source: CVD Statistics– BHF UK Factsheet – February 2018

CVD Prevention: Challenge!

Source: Alan Gregg (1890-1957), Rockefeller Foundation

“The human race has had long experience and a fine tradition in surviving adversity; we now face a task for which we have little experience, the task of surviving prosperity”

Deanfield  UCL

Obesity: Clear and Present Danger

“The commonest Instruments

• f suicide

are a knife and fork”

Martin Fischer

Jamie Oliver’s Healthy School Meals Who is responsible for our health? Child? Parents? Government?

Doctors? Advocates for political/ Societal change

Moscow PACE 2018 Source: Speaking at a conference on 18 May 2015

“First, as a nation it’s time to get our act together on prevention…we’ve got a choice. Condemn our children to a rising tide of avoidable diabetes, cardiovascular disease, cancer? And burden taxpayers with an NHS bill far exceeding an extra £8 billion by 2020? Or take wide ranging action – as families, as the health service, as government, as industry. It’s a no brainer – pull out all the stops

• n

prevention, or face the music.”

“The Next Five Years for the NHS” : Simon Stevens, Chief Executive NHS England

Obesity and CV Disease: Policy Interventions

Take Home Messages

➢ Incorporate evidence based treatments in

• ur care

➢ Work with colleagues and think about T2DM/CV Risk ➢ Prevention opportunities – primary and secondary ➢ Advocates for political and societal changes

Deanfield UCL 2018

Final Thought…

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

• Ernest L. Wynder M.D