THE BURDENOFHEART FAILURE

© 2015 Novartis Pharma AG, May 2015, GLCM/HTF/0027a

Heart Failure is a complex syndrome involving multiple organ systems and is associated with a high mortality and morbidity burden

• Heart failure (HF) is a chronic condition, punctuated by acute episodes

• Each acute event results in further organ damage: myocardial and renal damage occurring during such episodes may contribute to progressive left ventricular and/or renal dysfunction

• Increasing frequency of acute events with disease progression leads to higher rates of hospitalization and increased risk of mortality

Adapted from Gheorghiade et al. Am J Cardiol 2005;96:11–17; Gheorghiade and Pang. J Am Coll Cardiol 2009;53:557–73

Chronic decline

Cardiac functionand quality of life

Disease progression

Hospitalisations foracute decompensation episodes

Heart failure is a major and growing public health problem

MI=myocardial infarction; ‡Calculated using the incidence rate of HF in 1997 for the population in Hong Kong and applying it to the Chinese population1. Dickstein et al. Eur Heart J 2008;29:2388–442; 2. Go et al. Circulation 2013;127:e6–e245; 3. Allender et al. Coronary Heart Disease Statistics 2008; 4. Hung et al. Hong Kong Med J 2000;6:159–62; 5. Hunt et al. J Am Coll Cardiol 2009;53:e1–90; 6. Kearney et al. Lancet 2005; 365:217–23

Prevalence1 Growth5

As many as 1 in 5 people aged 70–80

years have HF1

Incidence2–4

new cases per 100,000 per year

219

130

70‡

2%

Improved post-MIsurvival5

Increasingprevalence

of riskfactors5,6

Agingpopulation5

HFPrevalence

of the population in Europe have HF1

HF is associated with significant mortalityMorbidity and mortality in Heart failure

HF=heart failure‡Data from European patients hospitalized for heart failure in the European Society of Cardiology Heart Failure (ESC-HF) Pilot study and EuroHeart Failure Survey (EHFS) II†Analysis of HF data from 1,282 incident cases of HF in the Atherosclerosis Risk in Communities (ARIC) population-based study of n=15,792 individuals from four communities in the USA (1987–2002)§Reported rates vary but some publications include rates up to 50%681.Maggioni et al. Eur J Heart Fail 2010;12:1076–84; 2. Nieminen et al. Eur Heart J 2006;27:2725–36; 3. Cleland et al. Eur Heart J 2003;24:442–636; 4. Loehr et al. Am J Cardiol 2008;101:1016–22; 5. Maggioni et al. Eur J Heart Fail 2013;15:808–17; 6. Roger et al. JAMA 2004;292:344–50;7. Levy et al. N Engl J Med 2002;347:1397–402; 8. Askoxylakis et al. BMC Cancer 2010;10:105

30 days

~10%

mortalityafter 30 days†4

1 year

~20%

mortalityafter 1 year‡5

5 years

Up to 50%

mortalityafter 5 years§6-8

Hospital

4-7%

in-hospital mortality rate‡1–3

post-diagnosis

HF with reduced EF and HF with preserved EF are associated with high levels of morbidity and mortality

Morbidity and mortality in Heart failure

‡Based on data comparing mortality and HF hospitalization rates from clinical trials in patients with HFpEF (n=3 trials) with similar data from clinical trials in patients of without HF but who were of a similar age, comorbidity profile and had other conditions that increase CV risk (stable angina pectoris [n=1 trial], diabetes [n=1 trial] or hypertension [n=5 trials]) CV=cardiovascular; EF=ejection fraction; HF=heart failure; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; LVEF=left ventricular ejection fraction1.Meta-Analysis Global Group In Chronic heart failure (MAGGIC). Eur Heart J 2012;33:1750–7; 2. Campbell et al. J Am Coll Cardiol 2012;60:2349–56; 3. McMurray et al. Eur Heart J 2012;33:1787–847

HF with reduced EF and HF with preserved EF are associated with high levels of mortality1

The prognosis for patients with chronic HF and preserved EF is substantially worse than that for patients with other conditions that increase CV risk‡2

No therapies are proven to reduce morbidity and mortality in chronic HF with preserved EF3

Mor

talit

y (%

)

40

30

20

10

0

HFpEF

HFrEF

0 1 2 3

Years

Heart failure has a significant impact on quality of life

*Data from patients receiving optimal medical therapy with chronic heart failure due to left ventricular systolic dysfunction and dysynchrony enrolled in the CARE-HF trial EQ-5D™ is a standardized instrument for use as a measure of health outcome, providing a simple descriptive profile and a single index value for health statusReprinted from the European Journal of Heart Failure, 7(2), Calvert MJ, et al. The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study, 243–51, Published on behalf of the European Society of Cardiology. All rights reserved, Copyright (2005) the authors, with permission of John Wiley & Sons, Inc.CARE-HF=CArdiac REsynchronisation in Heart Failure; HF=heart failureCalvert et al. Eur J Heart Fail 2005;7:243–51

Quality of life among patients with HF compared with the general population and other chronic conditions*

0.0 0.2 0.4 0.6 0.8 1.0

General population

General population aged 65-74

CARE-HF (Chronic heart failure)

Type II diabetes

Moderate motor neurone disease

Parkinson's disease

Non-small cell lung cancer

EQ-5Dindex score

Heart failure imposes a significant economic burden on the healthcare system

‡USA estimate includes direct costs (total annual medical spending) and indirect costs (lost productivity due to morbidity and mortality)1. Dickstein et al. Eur Heart J 2008;29:2388–442; 2. Hunt et al. J Am Coll Cardiol 2009;53:e1–90; 3. Heidenreich et al. Circulation 2013 [epub ahead of print]

~2%

of the total healthcare budget in many countries is spent on

the treatment of HF1

of the cost of HF is due to hospitalizations170%

of the cost of HF is due to pharmacological treatment2~10%

Due to an ageing population, the total cost of HF in the USA alone is expected to increase

by~127% 2030 ‡3

Many patients are discharged with unresolved congestion, which is associated with poor long-term outcomes

Unmet therapeutic need in acute Heart failure:

Number of signs of congestion after

discharge from hospital‡

Persistent congestion after hospitalizationfor HF predicts poor survival‡2

2-year mortality rate

‡Patients with New York Heart Association class IV heart failure (HF; n=146) were re-assessed for signs of congestion 4–6 weeks after discharge. Criteria for congestion were orthopnea, raised jugular venous pressure, the need to increase the dose of diuretic during the past week, attending staff assessment of weight, and peripheral edema1. Maggioni et al. Eur J Heart Fail 2010;12:1076–84; 2. Lucas et al. Am Heart J 2000;140:840–7

24%

of patients hospitalized for HFin Europe have signs of

congestion at discharge1

0

1–2

3–5

13%

33%

59%

HFrEF mortality remains high despite the introduction of new therapies that improve survival

Unmet therapeutic need in chronic Heart failure

4.5% ARR;mean follow up of

41.4 months

SOLVD1

5.5% ARR;mean follow up of

1.3 years

CIBIS-II3

Reduction inrelative riskof mortalityvs placebo

ACEI* β-blocker* MRA*

11.0% ARR;mean follow up of

24 months

RALES4

3.0% ARR;median follow-up of

33.7 months

CHARM-Alternative2

ARB*

*On top of standard therapy at the time of study (except in CHARM-Alternative where background ACEI therapy was excluded). Patient populations varied between trials and as such relative risk reductions cannot be directly compared. SOLVD (Studies of Left Ventricular Dysfunction), CIBIS-II (Cardiac Insufficiency Bisoprolol Study II) and RALES (Randomized Aldactone Evaluation Study) enrolled chronic HF patients with LVEF≤35%. CHARM-Alternative (Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity) enrolled chronic HF patients with LVEF≤40%. ARR=absolute risk reduction; HF=heart failure; MRA=mineralocorticoid receptor antagonist; RRR=relative risk reduction1. SOLVD Investigators. N Engl J Med 1991;325:293–302; 2. Granger et al. Lancet 2003;362:772–6; 3. CIBIS-II Investigators. Lancet 1999;353:9–13; 4. Pitt et al. N Engl J Med 1999;341:709-17; 5. Roger et al. JAMA 2004;292:344–50

HFrEF survival rates have improved over time with the introduction of new therapies

However, significant mortality remains5

16%

34%30%

17%

Summary

• Heart failure (HF) is a chronic condition, punctuated by acute episodes, which may affect multiple organ systems

• HF is associated with high morbidity and mortality and place a significant economic burden on healthcare systems

• Unresolved congestion at discharge is associated with poor long-term outcomes

• No therapies are proven to reduce morbidity and mortality in chronic HF with preserved EF

• The evidence base supporting long-term benefits of current treatments for acute HF is limited

• Early treatment with a therapy that targets the underlying pathophysiology of acute HF may improve long-term outcomes

• There is a need for therapeutic advances in HF