Diabetes and Cardiovascular Disease: Time for multifactorial - - PowerPoint PPT Presentation

Diabetes and Cardiovascular Disease: Time for multifactorial approach

Professor John Deanfield - University College London, UK December 2018

Dubai 2018

Diabetes Is Associated With Significant Loss of Life Years

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

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Major Diabetes Complications in USA

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CVD Admissions Hyperglycaemic Deaths

Dysglycaemia and CV risk: Impact of glucose perturbations in patients who have experienced MIs

Source: Ritsinger et al, Diab Vasc Dis Res 2015;12:23–32

GAMI – long-term follow-up First major event (death, MI, stroke, or severe HF)

DM, diabetes mellitus; GAMI, Glucose Tolerance in Patients with Acute Myocardial Infarction; HF, heart failure; IGT, impaired glucose tolerance; MI, myocardial infarction; NGT, normal glucose tolerance; Pat, patients

34% 35% 31% GAMI-pat

Pat + NGT Pat + DM Pat + IGT Log-rank overall: p=0.0046

Proportion of event-free survival Follow-up (years)

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

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Risk Factors for CVD in patients with T2DM

Source: Rawshani et al, N Engl J Med 2018;379:633-44

Stroke Heart Failure Death From Any Cause Acute Myocardial Infarction

271,174 pts with T2DM matched to 1,355,870 controls Median F/U = 5.7 years with 175,345 deaths

Benefit of different interventions per 200 patients with diabetes treated for 5 years

Using traditional glucose lowering treatments

Ray, Lancet 2009 Meta-analysis of intensive glucose-lowering trials.

Per 0.9% lower HbA1c Per 4mm Hg lower SBP Per 1mmol/L lower LDL-C CV Events 5

• 5
• 12.5
• 15
• 20
• 10
• 8.2
• 2.9

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Diabetes Medications and Increased CV Risk

Source: Nissen SE, Wolski K. N Engl J Med 2007; 356: 2457-2471

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

Diabetes Treatment for CVD Reduction

SGLT-2 Inhibitors GLP-1R Agonsits

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• Statins
• BP Lowering
• Metformin

SGLT2-i GLP1-RA

Evidence Based CV Risk Reduction

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).

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Medical History HF-REF (%) HF-PEF (%) p value IHD 48.4 37.9 <0.001 Atrial fibrillation 49.1 40 0.857 MI 30.7 18.1 <0.001 Valve disease 23.9 31.4 <0.001 Hypertension 52.1 59.9 <0.001

Diabetes 33.3 33.5 0.577

Asthma 8.4 9.4 <0.001 COPD 16.7 18.9 <0.001

Diabetes is very common in Heart Failure

➢ Cardiologists need to update themselves on good diabetes care ➢ Checking the “diabetes” checks have been done is quick ➢ Little additional work ➢ Get to know your local diabetologist and what GPs can offer ➢ Remember to screen for diabetes

(HbA1c ≥ 6.5% or FPG ≥ 7 mmol/l)

“Take home” messages

It is NOT that complicated… Surprise your patient: ask them about their diabetes!

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

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Novel ‘Diabetes’ Drugs: Unanswered Questions

Which patients benefit most from each drug? e.g. patients with HF or kidney disease Mechanisms by which drugs mediate CV benefit?

? ?

Are these drugs equally effective in patients without CVD or without DM (primary prevention)?

?

Future CVOTs

Heart failure Nephropathy Obesity

?

A Question for you…?

“Why do we want to be brilliant at treating illnesses that we could have prevented?”

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IDF Diabetes Atlas. 7th edn. 2015

2015 2040

Worldwide Rise In Diabetes

Gruber J and Frakes M. J Health Econ. www.sciencedirect.com.

0.35 0.3 0.25 0.2 0.15 0.1 0.05 0.4

Proportion

• f population

1970

Year

1974 1978 1982 1986 1990 1994 1998 2002

Obesity rate Smoking rate

Decline in smoking vs rise in obesity: A trade-off?

Obesity at 2 yrs predicts status at 35 yrs...

Ward et al, N Engl J Med 2017;377:2145-53

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BMI during adolescence and CV mortality

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

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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

Healthy Lifestyle and CVD in T2DM

Source: Lui, G et al, JACC 2018;71(25):2867-76

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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: CV Outcome in obese patients with CVD

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

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

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New Era for CVD Management in DM: Some Thoughts

▪ CVD and renal benefit with two new glucose lowering drug classes, SGLT2i and GLP1-RA ▪ Has already changed guidelines for DM care ▪ Novel multiple mechanisms, especially with lack of hypoglycaemia will broaden indications towards early treatment, prevention, even without DM

Diabetologists Cardiologists