Recent Successes in Heart Failure

Transcription

1 Recent Successes in Heart Failure Samer S. Najjar, M.D. Medical Director, Heart Failure and Heart Transplantation MedStar Heart and Vascular Institute MedStar Washington Hospital Center May 30, 2015

2 Presenter Disclosure Information Samer S. Najjar, MD FINANCIAL DISCLOSURE: Research Support: HeartWare Inc, Gambro Advisory Board: HeartWare Inc UNLABELED/UNAPPROVED USES DISCLOSURE: None

3 Recent Sucesses in Heart Failure Chronic Heart Failure Acute Decompensated Heart failure Heart Failure with Preserved Ejection Fraction Stage D Heart Failure

4 Heart Failure Epidemiology/Facts Prevalence: ~ 7 million in US (2.5%) Incidence: ~ 550,000/year Mortality: ~ 300,000/year Office visits: ~ 3.4 million (2004) Hospital discharges: ~ 1,000,000 (2001) Health care costs exceed $30 billion/year Single largest expense for Medicare

5 Percent of Population Heart Failure Prevalence Male Female Age References: American Heart Association. Heart Disease and Stroke Statistics 2005 Update. NHANES:

6 Projected Elderly Population >65 years (millions) Heart Failure Demographic Trends Elderly U.S. population will double in the next decade million 12.6% total US population 65.6 million 21.8% total US population

7 Estimated Direct and Indirect Costs of Heart Failure in the US Low productivity/ mortality* $2.6 Home healthcare $2.2 Total cost: $27.9 Billion Drugs/other medical durables $2.9 Physicians/other professionals $1.9 Hospitalization $14.7 Nursing home $3.6 Reference: * Lost future earnings of persons who will die in 2005, discounted by 3%. American Heart Association. Heart Disease and Stroke Statistics 2005 Update. NATRECOR (nesiritide) P

8 Annual Discharges Heart Failure Hospitalizations The Number of Heart Failure Hospitalizations Is Increasing in Both Men and Women 600, , , , , ,000 Women Men 0 '79 '81 '83 '85 '87 '89 '91 '93 '95 '97 '99 CDC/NCHS: hospital discharges include patients both living and dead. AHA Heart and Stroke Statistical Update Year

9 Heart Failure Pathophysiology Myocardial Injury Fall in LV Performance Activation of RAAS, SNS, ET, and Others Myocardial Toxicity ANP BNP Peripheral Vasoconstriction Hemodynamic Alterations Morbidity and Mortality Remodeling and Progressive Worsening of LV Function Heart Failure Symptoms Shah M, et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.

10 Therapies for Chronic HF by NYHA Class Therapy Class I Class II Class III Class IV Diuretics Digoxin ACE inhibitors ARBs Beta blockers Aldactone Hydralazine/nitrates ICD CRT Adapted from Almeda FQ, Hollenberg SM. Postgrad Med. 2003;113:41

11 Probability of Survival MADIT-II ICD vs. Conventional Rx % 28% 28% Defibrillator Group Conventional Group 0.69 P= Years N Engl J Med. 2002;346:

12 Ventricular Dyssynchrony

13 Effects of CRT on LV Performance Ejection Fraction (%) dp/dt max (mmhg/sec) Baseline 1wk 1mo 3mo offimmed off- 1wk off- 4wk 400 Baseline 1wk 1mo 3mo offimmed off- 1wk off- 4wk Yu CM, et al. Circulation. 2002;105:

14 Systolic Heart failure treatment with the I f inhibitor ivabradine Trial

15 Mean heart rate reduction Heart rate (bpm) 70% of patients on ivabradine 7.5 mg bid Placebo Ivabradine weeks Months Swedberg K, et al. Lancet. 2010;376(9744):

16 Primary composite endpoint (CV death or hospital admission for worsening HF) Cumulative frequency (%) HR = 0.82 ( ) P < Placebo 18% 20 Ivabradine Months Swedberg K, et al. Lancet. 2010;376(9744):

17 Hospitalization for HF Cumulative frequency (%) 30 HR = 0.74 ( ) P < Placebo 26% 20 Ivabradine Months Swedberg K, et al. Lancet. 2010;376(9744):

18 Death from heart failure Cumulative frequency (%) 10 HR = 0.74 ( ) P = Placebo 26% Ivabradine Months Swedberg K, et al. Lancet. 2010;376(9744):

19 Angiotensin-Neprilysin Inhibition vs. Enalapril in HF (PARADIGM-HF) McMurray JJ et al. N Engl J Med 2014;371:

20 Angiotensin-Neprilysin Inhibition vs. Enalapril in HF (PARADIGM-HF) McMurray JJV et al. N Engl J Med 2014;371:993-

21 Recent Successes in Heart Failure Chronic Heart Failure Acute Decompensated Heart failure Heart Failure with Preserved Ejection Fraction Stage D Heart Failure

22 Heart Failure Outcomes of Hospitalized Patients 100 Hospital Readmissions Mortality 100 N = 38,702 N = 38, % 50% % 33% 60% 0 30 Days 6 Months 0 30 Days 12 Months 5 Years Median length of hospital stay: 6 days References: Aghababian RV. Rev Cardiovasc Med. 2002;3(suppl 4):S3-S9. Jong P et al. Arch Intern Med. 2002;162:

23 Enrolled Discharges (%) Incomplete Relief of Congestion % 32% 20% of ADHF patients discharged with weight gain or no change in weight % 7% 13% 15% 3% 2% 0 (<-20) ( 20 to 15) (-15 to 10) ( 10 to 5) ( 5 to 0) (0 to 5) (5 to 10) (>10) Change in Weight (lbs)

24 DOSE trial Bolus vs. Continuous Diuretics Felker et al. N Engl J Med 2011; 364:

25 ASCEND-HF Nesiritide in patients with ADHF O Connor et al. N Engl J Med 2011; 365:32-43

26 Mechanical Fluid Removal by Ultrafiltration Interstitial Space (edema) P H 2 O Na UF K Na PR K P Na Vascular Space Vascular Space Na

27 Primary End Point Weight Loss at 48 Hr Costanzo J Am Coll Cardiol. 2007;49: APS

28 CARRESS-HF UF in ADHF with Cardiorenal Syndrome Bart BA et al. N Engl J Med 2012;367:

29 CARRESS-HF UF v. Diuretics May 19, Bart NEJM 2012

30 Recent Successes in Heart Failure Chronic Heart Failure Acute Decompensated Heart failure Heart Failure with Preserved Ejection Fraction Stage D Heart Failure

31 Tribouilloy Eur Heart J 2007; 29:339 Prevalence of HFPEF vs. SHF by Age Groups

32 Heart Failure Secular Trends in Survival Reduced EF Preserved EF Owan, N Engl J Med 2006; 355; 251

33 Recent Successes in Heart Failure Chronic Heart Failure Acute Decompensated Heart failure Heart Failure with Preserved Ejection Fraction Stage D Heart Failure

34 ACC/AHA Heart Failure Stages Jessup N Engl J Med 2003;348:

35 Therapies for End-Stage HF Hospice/Palliation Inotropes IABP Heart Transplantation Mechanical Assist Devices

36 Number of Transplants 4500 NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR Other Europe North America ISHLT J Heart Lung Transplant Oct; 29 (10):

37 Survival (%) ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: 1/1982 6/2006) All comparisons significant at p < (N=18,854) (N=35,146) /2006 (N=12,369) HALF-LIFE : 8.8 years; : 10.5 years; /2006: NA Years ISHLT 2008 J Heart Lung Transplant 2008;27:

38 Ventricular Assist Devices

39 REMATCH Trial LVAD - 48% p=0.001 Medical Rx Rose E et al NEJM 2001:345;

40 Ventricular Assist Devices HeartMate II HeartWare

41 Outcomes with LVAD vs. OMM Percent Survival % CF LVAD 58% 25% OMM REMATCH 8% N Engl J Med. 2009;361: Months * N Engl J Med 2001; 345:

42 HeartMate II Survival by Era Percent Survival Implant dates n 30 d 6 Mo 12 mo a Apr 08 - Oct % 89% 85% b Apr 08 - Aug % 90% 85% c Mar 07 - Apr % 86% 80% d Mar 05 - Mar % 82% 73% e Mar 05 - May % 75% 68% a John et al STS 2011 b Starling et al JACC (in press) d Pagani et al JACC 2009 e Miller et al NEJM Months Post-Trial a Post-Approval Study b Late Trial c Early-mid Trial d Early Trial e John, Naka, Smedira et al: Presented at STS 2011

43 Improvement in Functional Class Baseline 1 mth 3 mth 6 mth Rogers, J Am Coll Cardiol ;55(17):

44 Improvement in QOL (KCCQ) Rogers, J Am Coll Cardiol ;55(17):

45 Thoratec Next Generation Pumps HeartMate III HeartMate X Investigational Devices

46 HeartWare HVAD & MVAD Investigational Devices

47 Partial Support Circulite Investigational Device

48 LVAD Offered on ebay!

49 Advances in Heart Failure Therapy Chronic Heart Failure Acute Decompensated Heart failure X Heart Failure with Preserved Ejection Fraction X X Stage D Heart Failure

50 Prognosis Heart Failure vs. Cancer Mortality Pancreas Oesophagus Leukaemia Ovarian Colon Prostate Uterus Melanoma One year survival rate (%) The one-year survival rate for heart failure is worse than that for cancer of the breast, uterus, prostate & bladder Coronary heart disease statistics: heart failure supplement., BHF 2002, accessed Based on Quinn M et al. ONS 2001 & Cowie MR et al. Heart 2000; 83: NHL= Non-Hodgkins lymphoma

51 Prognosis Heart Failure vs. Cancer Mortality 1 Rose, Gelijns, Moskowitz, et al. NEJM. 345: , Rogers, Butler, Lansman, et al. J Am Coll Cardiol. 50:741-47, Hershberger, Nauman, Walker, et al. J Card Fail. 22:616-24, Gorodeski, Chu, Reese, et al. Circ Heart Fail. 2:320-24, 2009

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53 Back-Up Slides NATRECOR (nesiritide) P

54 Hemodynamic Profile Assessment Congestion at Rest Low Perfusion at Rest No Yes No Warm & Dry Cold & Dry Yes Warm & Wet Cold & Wet Signs/symptoms of congestion Orthopnea/PND JVD Ascites Edema Rales (rare in HF) Possible evidence of low perfusion Narrow pulse pressure Sleepy/obtunded Low serum sodium Cool extremities Hypotension with ACE inhibitor Renal dysfunction (one cause) Reference: Stevenson LW. Eur J Heart Fail. 1999;1:251. NATRECOR (nesiritide) P

55 Patient Selection and Treatment Congestion at Rest No Yes Low Perfusion at Rest No Yes Warm & Dry PCWP normal CI normal (compensated) Cold & Dry PCWP low/normal CI decreased Warm & Wet PCWP elevated CI normal Cold & Wet PCWP elevated CI decreased Normal SVR High SVR Vasodilators Nitroprusside Nitroglycerin Inotropic Drugs Dobutamine Milrinone Reference: Stevenson LW. Eur J Heart Fail. 1999;1:251. NATRECOR (nesiritide) P

56 Similarities Between Acute MI and Acute Decompensated HF Acute MI ADHF Incidence 1 million per year 1 million per year Mortality In-hospital 3 4% 3 4% After discharge (60 90 d) 2% 10% Pathophysiological target(s) Clinical benefits of interventions in published clinical trials ACC/AHA recommendations Clearly defined (coronary thrombosis) Beneficial Many Level A Uncertain Minimal/no benefit or deleterious compared with placebo None*** (Gheorghiade M, et al. Circulation 2005;112: )

57 Cost of End-Stage HF REMATCH Trial (OMM) Mean cost last 2 yrs: $156,169 $78,880 (50% last 6 mos) 1 in 4 days in last 6 months spent in the hospital 79% of all costs were for inpatient costs 28% for ICU care, 18% for outpatient care, 3.5% for MD professional fees Russo, M, et al. JCF. 2008;14(8):

58 LVAD costs compared with other lifesaving therapies LVAD implantation is both life-saving and resourceintensive. Costs are very similar to other high-tech interventions that society pays $200,000 $150,000 $100,000 $50,000 $0 $91,093 Heart Transplantation (1995) $53,000 Kidney Dialysis (2000) Total One Year Costs $160,000 Chemotherapy for Colon Cancer (2004) Per Initial Hospitalization $128,000 LVAD for DT (2004) Annual Medicare budget per heart transplant ($175,000) from delissovoy, Health Affairs, 1998 Annual Medicare payment for kidney dialysis ($53,000) from CMS, 2002 Twelve month cost of mab-based chemotherapy based on AWP for colon cancer ($161,000) from Schrag, NEJM, 2004 Average LVAD hospitalization costs ($128,084) for two of the highest-volume DT-accredited facilities (Miller et al, 2006) B

59 Natural History of Systolic HF

60 Survival After Hospitalization Miller, Guglin J Am Coll Cardiol. 2013;61(12):

61 Heart Failure Risk Stratification Cardiopulmonary Exercise Testing Prognostic Significance of Oxygen Consumption Albouaini Heart 2007;93: Mancini Circulation 1991;83:

62 Conclusion Ivabradine significantly reduces major risks associated with heart failure: 18% reduction in CV death or hospital admission for worsening HF 26% reduction in death from heart failure 26% reduction in hospital admission for worsening heart failure Benefits are apparent early, are consistent in predefined subgroups, and have been demonstrated on top of recommended therapy Treatment is well tolerated Swedberg K, et al. Lancet. 2010;376(9744):

63 Continuous Flow Physiology No PULSE Measurement of Blood Pressure

64 Angiotensin-Neprilysin Inhibition vs. Enalapril in HF (PARADIGM-HF) McMurray JJV et al. N Engl J Med 2014;371:

65 Angiotensin-Neprilysin Inhibition vs. Enalapril in HF (PARADIGM-HF) McMurray JJV et al. N Engl J Med 2014;371: