Heart Failure is not a disease It is a syndrome with many causes that have common symptoms
Prevalence estimates between studies varied because of differences in study population, case definition, and echocardiographic measurements applied. Eur J Heart Fail 2016;18:242-252
Prevalence of Heart Failure Eur J Heart Fail 2016;18:242-252
Prevalence of Heart Failure Eur J Heart Fail 2016;18:242-252
Cost of heart failure Heart Failure (1) £629 AIDS (2) £345 Breast Cancer (3) £243 Prostate Cancer (4) £63 £0 £100 £200 £300 £400 £500 £600 £700 Million £ / Year HF in the UK About 840,000 have HF £379 million annual hospitalization cost About 66,000 new cases each year 106,080 episodes / year £3,572 / episode in average 986,995 hospitalization days 13.3 days / episode in average 1.Cost of Heart Failure to the National Health Service, 2000, UK on the British Heart Foundation Website www.heartstats.org accessed on June the 13th 2006. 2. House of Commons Health Committee (2003), 'Sexual Health: Third Report of Session 2002-03', May, p. 46. 3. Dolan P. et al. Cost of breast cancer treatment in the UK. Breast. 1999 Aug; 8(4): 205-207. 4. Computed from Moss S. The diagnosis, management, treatment and costs of prostate cancer in England and Wales. The Research Findings Register. Summary number 25. Retrieved 13 June 2006, from http://www.RefFeR.nhs.uk
Estimated costs of heart failure Low productivity / mortality Total cost: $29.6 Billion Home healthcare Drugs/other medical durables Hospitalisation Physicians/other professionals $14.7 Nursing home American Heart Association. Heart Disease and Stroke Statistics – 2006 Update
70% of patients with HF are managed by primary care physicians
Neurohormonal Activation in Heart Failure Normal Heart Failure Renin- Arginine ANP/BNP Endothelin-1 Angiotensin- Norepinephrine Vasopressin Aldosterone 12 8 300 600 15 250 500 12 6 6 200 400 9 4 4 150 300 6 100 200 2 2 3 50 100 0 0 0 0 0 Adapted from Cohn JN. Cardiology, 1997;88:2-6
Pharmacological therapy indicated in potentially all patients with systolic HF Recommendations Class Level ACE inhibitor An ACE inhibitor is recommended, in addition to a beta-blocker, for all patients with an EF ≤40% to reduce the risk of HF hospitalization and the risk of premature I A death. Beta-blocker A beta-blocker is recommended, in addition to an ACE inhibitor (or ARB if ACE inhibitor not tolerated), for all patients with an EF ≤40% to reduce the risk of HF I A hospitalization and the risk of premature death. MRA An MRA is recommended for all patients with persisting symptoms (NYHA class II – IV) and an EF ≤35%, despite treatment with an ACE inhibitor (or an ARB if an ACE I A inhibitor is not tolerated) and a beta-blocker, to reduce the risk of HF hospitalization and the risk of premature death. All three 1A recommendations are neurohumoral modulators
Eur Heart J. 2016 May 20. http://dx.doi.org/10.1093/eurheartj/ehw128
HYPERKALEMIA AFTER RALES PUBLICATION N Eng J Med 2004;351:6:543-551
Figure 1. The Renin – Angiotensin – Aldosterone System. N Engl J Med, Vol. 345, No. 23
HOPE Trial with ramipril
ATMOSPHERE & PARADIGM: baseline characteristics (3/3) ATMOSPHERE PARADIGM Baseline Variables (n=7063) (n=8399) Diabetes mellitus, % 28% 35% Stroke, % 7% 9% Current smoker, % 13% 14% ECG findings Left bundle branch block, % 21% 20% QRS duration, ms 117 117 Pretrial use of ACEi/ARB Previous use of ACEi at screening visit, % 100% 78% Previous use of ARB at screening visit, % 2% 23% Pharmacological treatment Diuretic use, % 80% 80% Beta blocker, % 92% 93% MRA, % 37% 56% Digoxin, % 32% 30% Anticoagulant, % 30% 32% Lipid lowering, % 52% 56% Devices for HF at screening CRT, % 6% 7% ICD, % 15% 15% All values are from the randomization visit unless otherwise stated. Krum et al. Eur J Heart Fail (2015) 17, 1075 – 1083
ATMOSPHERE: Primary outcome
ATMOSPHERE: Safety outcomes Aliskiren+ Enalapril Aliskiren Enalapril P value P value (1) (n=2340) (n=2340) (n=2336) (2) Hypotension n (%) Symptoms 322 (13.8%) 249 (10.6%) 258 (11.0%) 0.005 0.67 Symptoms and SBP <90mmHg 87 (3.7%) 31 (1.3%) 55 (2.4%) 0.008 0.009 Renal impairment n (%) 95 (4.1%) 63 (2.7%) 62 (2.7%) 0.009 1.00 Cr ≥2.5mg/dl 46 (2.0%) 35 (1.5%) 29 (1.2%) 0.06 0.53 Cr ≥3.0mg/dl Hyperkalemia n (%) 401 (17.1%) 255 (10.9%) 291 (12.5%) <0.0001 0.10 K + >5.5mmol/l 116 (5.0%) 70 (3.0%) 83 (3.6%) 0.02 0.29 K + >6.0mmol/l Cough n (%) 290 (12.4%) 241 (10.3%) 284 (12.2%) 0.83 <0.05 (1) = Comparison of enalapril plus aliskiren versus enalapril; (2) = Comparison of aliskiren versus enalapril
PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint) 40 1117 Enalapril 32 Kaplan-Meier Estimate of (n=4212) 914 Cumulative Rates (%) 24 LCZ696 (n=4187) 16 HR = 0.80 (0.73-0.87) 8 P = 0.0000002 Number needed to treat = 21 0 0 180 360 540 720 900 1080 1260 Days After Randomization Patients at Risk LCZ696 4187 3922 3663 3018 2257 1544 896 249 Enalapril 4212 3883 3579 2922 2123 1488 853 236 N Engl J Med 2014;371:993-1004
Challenges of Hyperkalemia in At-Risk Patients • Associated with increased mortality • Frequent visits to the emergency department or urgent care when potassium levels increase • Fear of hyperkalemia can prevent prescribing or optimally dosing RAAS inhibitor therapy
Thank you for your attention this afternoon
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