The cost of heart failure in people with type 2 diabetes Marc Evans - PowerPoint PPT Presentation

The cost of heart failure in people with type 2 diabetes Marc Evans

Disclosures • I have received honoraria and research awards from Astra Zeneca, Novonordisk, Takeda, Novartis, MSD, NAPP

Factors to consider when choosin ing an anti-hyperglycaemic therapy Individualized Complexity of HbA 1c target regimen Factors affecting treatment choice Side-effect profile CVD profile ✓ € Weight and Adherence and Safety Value for money hypoglycaemia persistence CKD, chronic kidney disease; CVD, cardiovascular disease 1. Davies MJ et al. Diabetologia 2018;41:2669 – 701 3

What is value? value 1. the worth of something compared to the price paid or asked for it

Mechanisms of CV disease in diabetes 1,2 Diabetes-related factors Obesity-related factors • • Hyperglycaemia Inflammatory cytokines • • Advanced glycosylated end Adipokines • products Insulin resistance • • Oxidative stress Oxidative stress Hypertension/ Dyslipidaemia • haemodynamic-related factors Oxidative stress • • Metabolic demand Elevated LDL-cholesterol • • Oxidation Adducted lipoproteins • Tissue ischaemia • Endothelial dysfunction CV, cardiovascular; LDL, low-density lipoprotein 1. Low Wang CC et al. Circulation 2016;133:2459 – 502; 2. England BR et al. BMJ ;316:k1036 6 Item code: MINT/MINVK-18032 Date of preparation: Jan 2019

Long-term outcomes after acute myocardial infarction are worse in patients with diabetes than in those without 1 Post MI mortality in patients with and without diabetes 40 Diabetes No diabetes Reductions in early mortality in all 1995 patients with acute MI were not sustained over the long term in those 1995 30 Cumulative mortality (%) 2003 with diabetes 2003 20 10 P = 0.506 P = 0.003 0 0 100 200 300 400 500 0 100 200 300 400 500 Time (days) Time (days) 221 157 154 153 146 140 1541 1201 1167 1132 1109 1084 272 213 201 189 185 176 1370 1146 1110 1073 1050 1030 Highlighted areas in Kaplan – Meier curves represent survival improvement within each group between 1995 and 2003 CI, confidence interval; MI, myocardial infarction 1. Cubbon RM et al. Eur Heart J 2007;376:540 – 5 7 Item code: MINT/MINVK-18032 Date of preparation: Jan 2019

Cardiac remodelling is a feature of T2D Hyperglycaemia, insulin resistance, obesity 1 Inflammatory Altered substrate Increased oxidative Mitochondrial cytokine release utilization: FFAs used stress 1 dysfunction 1 from adipose tissue 1 instead of glucose 1 Cardiac fibrosis that may reduce Left ventricular hypertrophy 1 myocardial compliance 2 Heart failure FFA, free fatty acid 1. Boudina S et al. Rev Endocr Metab Disord 2010;11:31 – 9; 2. Russo I et al. J Mol Cell Cardiol 2016;90:84 – 93 8 Item code: MINT/MINVK-18032 Date of preparation: Jan 2019

Diabetes worsens heart failure prognosis 1 Poorer HF survival in patients with diabetes than in those without diabetes LVEF ≥ 50% (n = 498) LVEF < 50% (n = 754) ) 1.0 1.0 Diabetes No diabetes Diabetes No diabetes 0.8 0.8 Survival proportion Survival proportion 0.6 0.6 0.4 0.4 0.2 0.2 0.0 0.0 0 2 4 6 8 10 12 0 2 4 6 8 10 12 Time (years) Time (years) RR = 1.73; p < 0.0001 RR = 1.41; p 0.0322 HF, heart failure; LVEF, left ventricular ejection fraction; RR, relative risk 1. Varela-Roman A et al. Eur J Heart Failure 2005;7:859 Item code: MINT/MINVK-18032 Date of preparation: Jan 2019

Hyperglycaemia and haemodynamic effects lead to structural changes in the kidney Renin – angiotensin system activation 1 Inflammation 1 Oxidative stress 1 Thickening of arteriole wall 2 Mesangial cell hypertrophy 2 Efferent arteriolar occlusion 1 Basement membrane thickening 2 Glomerular hypertension, hyperfiltration, albuminuria, reduced eGFR 2 eGFR, estimated glomerular filtration rate 1. Toth-Manikowski S et al. J Diabetes Res 2015;2015:697010; 2. Reidy K et al. J Clin Invest 2014;124:2333 – 40 10 Item code: MINT/MINVK-18032 Date of preparation: Jan 2019

CV damage, heart failure and kidney failure are intrinsically linked 1,2 • Inflammation Body weight Hyperglycaemia • Fuel shift Lipids • Oxidative stress • Myocardial dysfunction • Hyperfiltration • Intraglomerular pressure • Albuminuria Heart failure Sympathetic nervous system • Blood pressure activation • Angiotensinogen • Endothelins • TGF- β Fibrosis CKD/DKD progression CKD, chronic kidney disease; CV, cardiovascular; DKD, diabetic kidney disease; TGF- β , transforming growth factor β 1. Bongartz L et al. Eur Heart J 2005;26:11; 2. Wanner C et al. Diabetologia 2018;61:2134 – 9 11 Item code: MINT/MINVK-18032 Date of preparation: Jan 2019

Cost drivers in diabetes • Overall cost of diabetes in UK in 2010/11: £23.7bn • £9.8bn related to direct costs; £13.9bn indirect costs Total Direct Costs (£000s) £6,000 2010/11 2035/36 £5,000 £4,000 £3,000 £2,000 £1,000 £0 Hex et al. Diabetic Medicine 2012;29:855 – 62.

CV disease contributes 20 – 49% of total direct costs of treating T2D globally 1 Systematic review: average healthcare costs per patient per year (USD, 2016) 18000 Healthcare costs (USD) 15000 45% 12000 9000 Average annual costs to treat a patient 6000 with T2D 3000 • USD8310 without CV complications • 0 USD15 105 with CV complications CV disease Coronary artery Heart failure Stroke disease T2D without CV complications T2D with CV complications CV, cardiovascular; USD, US dollar 1. Einarson TR et al. Value Health 2018;21:881 – 90 13 Item code: MINT/MINVK-18036 Date of preparation: Jan 2019

Diabetes and heart failure often go hand in hand Age-associated prevalence of heart failure in individuals with and without diabetes 1 400 With diabetes 10 – 30% of patients with Without diabetes 350 T2D also have heart failure 2 300 Prevalence per 1000 250 200 150 100 Approximately 30% of all patients with heart failure also have T2D 2 50 0 < 45 45 – 54 55 – 64 65 – 74 75 – 84 85 – 94 Age at baseline (years) 1. Gilbert RE et al. Lancet 2015;385:2107 – 17; 2. Seferovic PM et al. Eur J Heart Failure 2018;20:853 – 72 14 Item code: MINT/MINVK-18035 Date of preparation: Jan 2019

An increase in heart failure risk is observed in patients with pre-diabetes 1 15 20 Adjusted incidence of heart failure Risk of heart failure begins Proportion of population (%) 15 (per 1000 patient-years) to rise steeply in patients 10 with pre-diabetes (HbA 1c < 5.7%) 10 5 5 0 0 4.5 5.0 5.5 6.0 6.5 HbA 1c (%) 1. Matsushita K et al. Diabetes 2010;59:2020 – 6 15 Item code: MINT/MINVK-18035 Date of preparation: Jan 2019

Heart failure prognosis is worse in patients with diabetes than in patients without diabetes 1 CV death or hospitalization due to heart failure in patients with diabetes stratified by ejection fraction category Heart failure with 60 With diabetes reduced ejection fraction HFrEF HFpEF HR 1.60 Without diabetes 95% CI 1.44 – 1.77 HFrEF Cumulative incidence (%) p < 0.0001 HFpEF 40 Heart failure with preserved ejection fraction 20 HR 2.0 95% CI 1.70 – 2.36 p < 0.0001 0 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Follow-up (years) CI, confidence interval; CV, cardiovascular; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio 1. MacDonald MR et al. Eur Heart J 2008;29:1377 16 Item code: MINT/MINVK-18035 Date of preparation: Jan 2019

Heart failure is an under-recognized complication of T2D Distribution of initial presentation of CV disease in patients with T2D a,1 9% PAD 16% Heart failure 10% Angina Stroke 14% 8% MI TIA 12% Coronary disease not specified 16% Other b 15% a N = 6137 events; b Unheralded CV death, abdominal aortic aneurysm, intercranial haemorrhage, subarachnoid haemorrhage, arrhythmia or sudden CV death CV, cardiovascular; HFpEF, heart failure with preserved ejection fraction; MI, myocardial infarction; PAD, peripheral artery disease; TIA, transient ischaemic attack 1. Shah AD et al. Lancet Diabetes Endocrinol 2015;3:105 – 13; 2. Altara R et al. Front Endocrinol 2017;8:160 17 Item code: MINT/MINVK-18035 Date of preparation: Jan 2019

The cost of treating heart failure is expected to rise over the coming decades 1 By 2030, one in every 33 60 people in the USA is projected 50 53.1 to have heart failure Cost (billions USD) +154% 40 30 31.1 The total direct and indirect 20 20.9 costs of treating heart failure 16.6 10 are expected to rise to 12.5 9.8 ~ USD70 billion by 2030 0 2012 2020 2030 Year Direct costs of Indirect costs of lost productivity from medical care morbidity and premature mortality USD, US dollar 1. Heidenreich PA et al. Circ Heart Fail 2013;6:606 – 19 18 Item code: MINT/MINVK-18036 Date of preparation: Jan 2019