Download Challenges and opportunities in heart failure: unmet clinical needs

Challenges and
opportunities in heart
failure: unmet clinical
needs, economic burden,
and impact on society
7 November 2015
Milan, Italy
Clinical unmet needs in
heart failure treatment
Joe Gallagher
University College Dublin
Ireland
Agenda
• Incidence and mortality of HF
• HF clinical needs
– early diagnosis
– HF-PEF treatment
– HF-REF treatment
• Where to next?
What is it?
• Heart failure (HF) is defined, clinically, as a syndrome in
which patients have typical symptoms (e.g.
breathlessness, ankle swelling, and fatigue) and signs
(e.g. elevated jugular venous pressure, pulmonary
crackles, and displaced apex beat) resulting from an
abnormality of cardiac structure or function
• It is a chronic condition with episodes of acute
decompensation
McMurray JJ, et al. Eur Heart J. 2012;33:1787-847.
Two main types
HF with preserved
ejection fraction
(HF-PEF)
HF with reduced
ejection fraction
(HF-REF)
Diastolic HF
Systolic HF
Aorta
Left
ventricle
Right
ventricle
Thick and stiff heart muscle
Thin and weak heart muscle
McMurray JJ, et al. Eur Heart J. 2012;33:1787-847.
Incidence
Prevalence1
MI, myocardial infarction.
Growth2
1. Dickstein K, et al. Eur Heart J. 2008;29:2388-442.
2. Hunt SA, et al. J Am Coll Cardiol. 2009;53:e1-e90.
Quality of life similar in HF and dialysis
patients
100
90
Dialysis
SF-36 score (%)
80
70
60
50
40
CHF
Depression
Dialysis
Hepatitis
Norm pop.
30
20
Heart failure
10
0
PF
RP
BP
GH
VT
SF
RE
MH
SF-36 scales
BP, bodily pain; CHF, congestive heart failure; GH, general health perceptions; MH, mental health; PF,
physical functioning; pop., population; RE, role limitations caused by emotional problems; RP, role limitations
due to physical limitations; SF, social functioning; SF-36, Short Form 36 health survey; VT, vitality.
Juenger J, et al. Heart. 2002;87:235-41.
Acute HF is associated with a lengthy
hospital stay
Median length of
hospitalization is
8 days
48% of hospitalized
patients will require
admission to the ICU for a
median period of 4 days
Data from 1,892 European patients with acute HF in the European Society of Cardiology Heart Failure (ESC-HF) pilot study
ICU, intensive care unit.
Maggioni AP, et al. Eur J Heart Fail. 2010;12:1076-84.
Time to rehospitalization decreased with
each subsequent event
Time to next event (mortality or readmission)
is shortened after every rehospitalization3a
Patients hospitalized for acute HF in
Europe are rehospitalized for HF
within 1 year1
Hospital admissions in
prior 6 months (n)
Median time to death or readmission
Increases with each
hospitalization for HF2
a Data
from 1,433 patients with ACC/AHA chronic “Stage D” HF (persistent symptoms and high risk of hospitalization
despite maximum medical therapy) enrolled in ADHERE LM. Data presented show time from entry in ADHERE LM for
50% of patients to be rehospitalized or die in 3 cohorts of patients defined by the number of hospitalizations experienced
in the 6-months prior to registry entry.
ACC, American College of Cardiology; ADHERE LM, Acute
Decompensated Heart Failure National Registry Longitudinal
Module; AHA, American Heart Association.
1. Maggioni AP, et al. Eur J Heart Fail. 2013;15:808-17.
2. Solomon SD, et al. Circulation. 2007;116:1482-7.
3. Costanzo MR, et al. Am Heart J. 2008;155:339-47.
HF is as “malignant” as many cancer
types
Stewart S, et al. Eur J Heart Fail. 2001;3:315-22.
Hospitalized HF patients have a
10% mortality by 30 days post discharge
3.8%
in-hospital
mortality rate1
~10%
mortality after
30 days2
1. Maggioni AP, et al. Eur J Heart Fail. 2010;12:1076-84.
2. Loehr LR, et al. Am J Cardiol. 2008;101:1016-22.
HF patients in the community have only
50% survival at 5 years
Study
Survival rates (%)
Hillingdon Study (2000)1
18-month survival: 57
Framingham (2002)2
5-year survival: males 41; females 55
Mayo Clinic (2004)3
5-year survival: 52
ECHOES study (2007,
2012)4,5
5-year survival: 534
10-year survival: 26.75
Olmsted County Study (2008)6
5-year survival: 45
Sweden (2013)7
5-year survival: 48
1. Cowie MR, et al. Heart. 2000;83:505-10.
2. Levy D, et al. N Engl J Med. 2002;347:1397-402.
3. Roger VL, et al. JAMA. 2004;292:344-50.
4. Hobbs FD, et al. Eur Heart J. 2007;28:1128-34.
5. Taylor CJ, et al. Eur J Heart Fail. 2012;14;176-84.
6. Henkel DM, et a. Circ Heart Fail. 2008;1:91-7.
7. Zarrinkoub R, et al. Eur J Heart Fail. 2013;15:995-1002.
HF is a progressive disease
Adapted from Gheorghiade M, et al. Am J Cardiol. 2005;96:11G-17G.
“The very essence of cardiovascular
medicine is the recognition of early
heart failure”
Sir Thomas Lewis (1933)
Diagnosis problems
• 34% of patients with an existing clinical label of
HF in general practice records had this diagnosis
confirmed by echocardiography1
• Most patients are diagnosed based on symptoms
and signs alone, with only 32% having further
investigations or referral2
1, Hobbs FD, et al. BMJ. 2002;324:1498.
2. Hobbs FD, et al. Eur Heart J. 2000;21:1877-87.
Missed diagnosis in primary care
1.
2.
3.
4.
5.
Pneumonia (6.7%)
Decompensated HF (5.7%)
Acute renal failure (5.3%)
Cancer (primary) (5.3%)
Urinary tract infection or pyelonephritis (4.8%)
Singh H, et al. JAMA Intern Med. 2013;173:418-25.
In Scotland, most people with any
long-term condition have comorbidities
This condition only
This condition + 2 others
HF
Stroke/TIA
Atrial fibrillation
Coronary heart disease
Painful condition
Diabetes
COPD
Hypertension
Cancer
Epilepsy
Asthma
Dementia
Anxiety
Schizophrenia/bipolar
Depression
9.2
2.8
13.6
6
14.1
18
6.5
12.7
16.3
8.8
16.3
19
12.7
20.7
14.3
20
17.6
18.6
21.9
23.9
23.3
20.6
31.4
47.5
5.3
12.7
17.8
7.1
17.1
19.9
12.7
20.7
23.4
22.3
0
This condition + 1 other
This condition + 3 or more others
20
74.4
61.9
64.5
55.9
20.6
19.1
16.8
46
46.6
47
19.3
17.4
23.1
16.3
19.5
11.8
34.9
38.7
29.2
21.2
64.2
55.9
20.6
46
18
40
36.3
60
80
100
Patients with each condition who also have comorbidities (%)
COPD, chronic obstructive pulmonary disease;
TIA, transient ischaemic attack.
Primary Care Clinical Informatics Unit, Scotland.
Clinical trials show reduced risk of
mortality with HF medications
Reduction in relative risk of
mortality vs placebo
ACEIa
BBa
MRAa
34%
(mean follow-up
of 24 months)
RALES
(1999)3
16%
(mean follow-up
of 41.4 months)
SOLVD
(1991)1
30%
(mean follow-up
of 1.3 years)
CIBIS-II
(1999)2
~40%
mortality after
5 years4b
a In
addition to standard of care at the time of study. Patient populations varied between trials; therefore RRR between trials 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 left ventricular ejection fraction ≤ 35%.
b Analysis of HF data from 1,282 incident cases of HF in the Atherosclerosis Risk in Communities (ARIC) population-based study of
15,792 individuals from 4 communities in the USA (1987–2002).
ACEI, angiotensin-converting enzyme inhibitor; BB, beta-blocker; MRA,
mineralocorticoid receptor antagonist; RRR, relative risk reduction.
1. SOLVD Investigators. N Engl J Med. 1991;325:293-302.
2. CIBIS-II Investigators. Lancet. 1999;353:9-13.
3. Pitt B, et al. N Engl J Med. 1999;341:709-17.
4. Loehr LR, et al. Am J Cardiol. 2008;101:1016-22.
No treatment has yet been shown,
convincingly, to reduce morbidity and
mortality in patients with HF-PEF
McMurray JJ, et al. Eur Heart J. 2012;33:1787-847.
Do we need new therapy?
• Mortality rates are still high – approx. 50% at 5 years1–5
• No disease-modifying treatments are available for HF-PEF6
• There is a new therapeutic option targeting the natriuretic
peptide system
• PARADIGM-HF prospectively compared ARNI and ACEI to
determine the impact on global mortality and morbidity in HF7
– LCZ696, compared with a target-dose enalapril-based regimen,
significantly reduced the rates of death from any cause and from
cardiovascular causes and the rates of hospitalizations for
worsening HF in patients with HF-REF
– Quality of life was significantly improved
• PARAGON-HF is an ongoing study comparing LCZ696 with
valsartan in patients with HF-PEF8
ARNI, angiotensin receptor–neprilysin inhibitor;
ACEI, angiotensin-converting-enzyme inhibitor.
1. Levy D, et al. N Engl J Med. 2002;347:1397-402. 2. Roger VL, et al. JAMA. 2004;292:344-50.
3. Hobbs FD, et al. Eur Heart J. 2007;28:1128-34. 4. Henkel DM, et a. Circ Heart Fail. 2008;1:91-7.
5. Zarrinkoub R, et al. Eur J Heart Fail. 2013;15:995-1002. 6. McMurray JJ, et al. Eur Heart J.
2012;33:1787-847. 7. McMurray JJ, et al. N Engl J Med. 2014;371:993-1004. 8. NCT01920711. Available
from: https://clinicaltrials.gov/ct2/show/NCT01920711. Accessed November 2015.
Where to next?
Life-years gained from early application
of therapy in HF-REF
Time
horizon
(years)
Life-years gained (years)
Men
Women
Overall
ACEI
ACEI + BB
ACEI
ACEI + BB
3
0.104
0.307
0.113
0.326
0.163
5
0.150
0.459
0.174
0.511
0.247
10
0.218
0.697
0.278
0.854
0.390
Mant J, et al. Health Technol Assess. 2009;13:1-207.
National Geographic Magazine January 2012.
Personalized medicine
“This year, the [clinical practice guidelines] reflect
the increasing use of evidence-based
recommendations in addition to the recognition
that the population-based evidence derived
from studies needs to be tailored to the
individual patient”
Richard Grant, MD, MPH, incoming chair of the American Diabetic
Association Professional Practice Committee 2013
Personalized HF prevention
• Use natriuretic peptides to identify patients at highest risk
of developing HF and to target care to this group
• STOP HF study1
– HF and LV dysfunction (odds ratio [OR] 0.55, 95% CI 0.37–0.82;
p = 0.003)
– hospitalization for major cardiac events (incidence rate ratio 0.60,
95% CI 0.45–0.81; p = 0.002)
• PONTIAC study2
– hospitalization for major cardiac event or cardiac death (hazard
ratio [HR] 0.351, 95% CI 0.127–0.975; p = 0.044)
• Will be further explored in the PARABLE study using
LCZ696 in those patients with mildly elevated natriuretic
peptide levels and cardiovascular risk factors3
CI, confidence interval; LV left ventricular.
1. Ledwidge M, et al. JAMA. 2013;310:66-74.
2. Huelsmann M, et al. J Am Coll Cardiol. 2013;62:1365-72.
3. PARABLE study. Available from: http://heartbeattrust.org/resources/IHF%20Day
%20Release%202015%20FINAL.pdf. Accessed November 2015.
Personalized Healthcare and Health Technology Assessment. Available from:
http://www.ceb-institute.org/bbs/wp-content/uploads/2013/06/2.1-Grueger130604-BBS-and-EFSPI-HTA-Allschwil.pdf. Accessed October 2015.
Challenges and
opportunities in heart
failure: unmet clinical
needs, economic burden,
and impact on society
7 November 2015
Milan, Italy