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 Vascular deaths Non-vascular deaths 7 Men Women 6 7 5 Years of life lost 6 4 5 3 4 2 3 1 2 0 1 0 40 50 60 70 80 90 0 40 50 60 70 80 90 0 Age (years) Age (years) 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 Source: Seshasai et al, N Engl J Med 2011; 364:829-41 PACE Dubai 2018

Major Diabetes Complications in USA Hyperglycaemic Deaths CVD Admissions PACE Dubai 2018 PACE Dubai 2018

Dysglycaemia and CV risk: Impact of glucose perturbations in patients who have experienced MIs GAMI – long-term follow-up First major event (death, MI, stroke, or severe HF) GAMI-pat Proportion of event-free survival Pat + NGT 31% 34% Pat + DM Pat + IGT Log-rank overall: p=0.0046 35% Follow-up (years) 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 Source: Ritsinger et al, Diab Vasc Dis Res 2015;12:23 – 32 PACE Dubai 2018

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

Risk Factors for CVD in patients with T2DM 271,174 pts with T2DM matched to 1,355,870 controls Median F/U = 5.7 years with 175,345 deaths Death From Any Cause Acute Myocardial Infarction Stroke Heart Failure Source: Rawshani et al, N Engl J Med 2018;379:633-44 PACE Dubai 2018

Benefit of different interventions per 200 patients with diabetes treated for 5 years Using traditional glucose lowering treatments 5 Per 4mm Hg Per 1mmol/L Per 0.9% lower SBP lower LDL-C lower HbA 1c 0 CV Events -2.9 -5 -8.2 -10 -12.5 -15 -20 Ray, Lancet 2009 Meta-analysis of intensive glucose-lowering trials. PACE Dubai 2018

Diabetes Medications and Increased CV Risk Source: Nissen SE, Wolski K. N Engl J Med 2007; 356: 2457-2471 PACE Dubai 2018

Diabetes Treatment for CVD Reduction SGLT-2 Inhibitors GLP-1R Agonsits Source: Newman JD, et al, J Am Coll Cardiol 2018; 72(15):1856-69 PACE Dubai 2018

Evidence Based CV Risk Reduction • Statins • BP Lowering • Metformin GLP1-RA SGLT2-i PACE Dubai 2018

CVOT Impact on Clinical Guidelines 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). Source: American Diabetes Association. Diabetes Care 2018;41 (Suppl 1):S73 – S85 PACE Dubai 2018

Diabetes is very common in Heart Failure 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 <0.001 Valve disease 23.9 31.4 <0.001 Hypertension 52.1 59.9 Diabetes 33.3 33.5 0.577 <0.001 Asthma 8.4 9.4 <0.001 COPD 16.7 18.9

“Take home” messages ➢ Cardiologists need to update themselves on It is NOT that good diabetes care complicated… ➢ Checking the “diabetes” checks have been done is quick Surprise your patient: ➢ Little additional work ask them about ➢ Get to know your local diabetologist and their diabetes! what GPs can offer ➢ Remember to screen for diabetes (HbA1c ≥ 6.5% or FPG ≥ 7 mmol/l) PACE Dubai 2018

GLP-1RA CV Outcome Trials SUSTAIN 6 LEADER Time to first occurrence of CV death, non-fatal MI or non-fatal stroke 2 0 HR: 0.74 (95% CI: 0.58 ; 0.95) p <0.001 for non-inferiority Patients with event (%) HR: 0.87 p =0.02 for superiority Patients with event (%) (95% CI: 0.78 ; 0.97) Placebo 1 5 p <0.001 for non-inferiority p =0.01 for superiority Placebo 1 0 Liraglutide Semaglutide 5 0 0 6 1 2 1 8 2 4 3 0 3 6 4 2 4 8 5 4 Time from randomisation (months) Time from randomisation (months) Marso SP et al. N Engl J Med 2016;375:311 – 322 Marso SP et al. N Engl J Med 2016;375:1834 – 1844

Novel ‘Diabetes’ Drugs: Unanswered Questions ? ? ? Which patients benefit Are these drugs equally Mechanisms by most from each drug? effective in patients without which drugs mediate CVD or without DM e.g. patients with HF or CV benefit? (primary prevention)? kidney disease ? Nephropathy Heart failure Obesity Future CVOTs PACE Dubai 2018

A Question for you…? “Why do we want to be brilliant at treating illnesses that we could have prevented ?” PACE Dubai 2018

Worldwide Rise In Diabetes Decline in smoking vs rise in obesity: A trade-off? 0.4 Smoking 0.35 rate 0.3 Proportion 0.25 of population 0.2 Obesity rate 0.15 0.1 0.05 0 2015 2040 1970 1974 1978 1982 1986 1990 1994 1998 2002 Year IDF Diabetes Atlas. 7th edn. 2015 Gruber J and Frakes M. J Health Econ. www.sciencedirect.com.

Obesity at 2 yrs predicts status at 35 yrs... PACE Dubai 2018 Ward et al, N Engl J Med 2017;377:2145-53

BMI during adolescence and CV mortality PACE Dubai 2018 Twig G et al, NEJM 2016;374:2430-40

The Ticking Clock:  CV Risk Before  Glucose (Nurses’ Health Study) 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 6.0 Relative risk of MI or stroke 5.02 5.0 4.0 3.71 2.82 3.0 2.0 1.0 1.0 0.0 Nondiabetic Risk of event Risk of event Diabetic throughout prior to after DM at B/L the study DM diagnosis diagnosis Source: Hu et al, Diabetes Care 2002; 25: 1129-1134 PACE Dubai 2018

Healthy Lifestyle and CVD in T2DM Source: Lui, G et al, JACC 2018;71(25):2867-76 PACE Dubai 2018

SELECT: CV Outcome in obese patients with CVD Semaglutide s.c. 2.4 mg once-weekly N=17,500 patients Male or female Placebo s.c. once-weekly ≥45 years of age BMI ≥ 27 Event driven Randomisation (1:1) 1225 first MACEs Primary endpoint: Time from randomisation to first occurrence of a Prior Prior composite endpoint consisting of either: PAD • CV death MI stroke • Non-fatal myocardial infarction • Non-fatal stroke

New Era for CVD Management in DM: Some Thoughts Diabetologists Cardiologists ▪ 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 PACE Dubai 2018