Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Electrocardiography wikipedia , lookup
Antihypertensive drug wikipedia , lookup
Coronary artery disease wikipedia , lookup
Heart failure wikipedia , lookup
Management of acute coronary syndrome wikipedia , lookup
Remote ischemic conditioning wikipedia , lookup
Cardiac contractility modulation wikipedia , lookup
Heart arrhythmia wikipedia , lookup
Dextro-Transposition of the great arteries wikipedia , lookup
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