ROSE-AHF and Beyond. Gerasimos Filippatos, FESC, FHFA President Heart Failure Association

Transcription

1 ROSE-AHF and Beyond Gerasimos Filippatos, FESC, FHFA President Heart Failure Association

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3 From: Braunwald s Heart Disease. 9th ed. Philadelphia, Elsevier, 2011

4 Determinants and forms of worsening renal function in heart failure. Filippatos G et al. Eur Heart J 2013;eurheartj.eht515

5 Decompensated chronic HF Consider higher dose of diuretics in renal dysfunction or with chronic diuretic use. ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

6 What to do next? 1. Increase furosemide dose 2. Ιntravenous infusion rather than bolus therapy 3. Substitution of an ineffective loop diuretic for another one 4. Add metolazone and/ or potasium sparing diuretic 5. Add dopamine at 2-5 mcg/k/m 6. Withdraw b-blocker and/ or ACE inhibitor 7. Add dobutamine 8. Add levosimendan 9. Start ultrafiltration 10. Start dialysis 11. Insert IABP 12. Insert another device Maisel A, Filippatos G, Heart Failure. Publisher Jaypoor Brothers, 2014

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8 Renal effects of dopamine Is a catecholamine-like agent. Increases in RBF and diuresis in animals and healthy subjects (1). Blunts vasoconstrictor effects of NOREPI on renal vasculature (2). Renal vasodilation at low doses ( μg/kg/min) mediated by DA-1 receptors (3). Decreases ALDO concentration with consequent increase in urine output and urine sodium concentration (4). Directly increases natriuresis mediated by the dopamine receptors (DA-1 through DA-5) in proximal tubule, thick ascending loop of Henle, and cortical collecting ducts (5). Stimulates antioxidant activity and counteregulates ANGII signalling, therefore decreasing renal fibrosis (6). 1. Olsen. Br J Clin Pharmacol 1997; 2. Hoogenberg. Crit Care Med 1998;26:260-5; 3. Lee. Clin Sci (Lond) 1993;84:357-75; 4. Dick. Ann Pharmacother 1994;28:837-41; 5. Seri. Am J Physiol 1990;258:F52-F60; 6. Gildea. Curr Opin Nephrol Hypertens 2009;18:28-32.

9 Renal Function Stabilized R

10 DAD-HF Pitfalls Did not include a low-dose furosemide (LDF) arm without dopamine infusion (is it the dopamine infusion per se or just the LDF renoprotective?).

11 DAD-HF II Trial 161 Patients with ADHF were prospectively randomized to receiving an 8 hour continuous infusion of: Group A Group B Group C high-dose furosemide (20 mg/h) HDF, N=50 Low-dose furosemide (5 mg/h) and low-dose dopamine (5 μg kg -1 min -1 ) LDFD, N=56 Low-dose furosemide (5 mg/h) LDF, N=55

12 The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial 1-year mortality (A) or mortality/rehospitalization for worsening heart failure (WHF) (B). HDF: high-dose furosemide; LDFD: low-dose furosemide plus low-dose dopamine; LDF: low-dose furosemide. FK. Triposkiadis, J Butler, G. Karayannis, RC. Starling, et al Int J Cardiol 2014

13 Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF): A Randomized Clinical Trial Horng H Chen MD on behalf of thenhlbi HF Clinical Research Network

14 Background AHF + Renal Dysfunction Patients with acute heart failure (AHF) and renal dysfunction are at risk for inadequate decongestion and worsening renal function factors associated with adverse clinical outcomes.

15 Hypotheses Novel study design In patients with AHF and renal dysfunction: I. As compared to placebo, the addition of low dose dopamine (2 g/kg/min) to diuretic therapy will enhance decongestion and preserve renal function II. As compared to placebo, the addition of low dose nesiritide (0.005 g/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function.

16 Study Design Standardized Diuretic Dosing For 1 st 24 hours 2.5 x Outpt Furosemide Equivalent in Divided (BID) IV Doses

17 Co-Primary Endpoints Decongestion Endpoint: Cumulative urinary volume from randomization through 72 hours Renal Function Endpoint : Change in serum cystatin-c from randomization to 72 hours

18 Baseline Characteristics Characteristic All patients (n=360) Age (years) 70 Male 73% AHF hsp in past year 67% Ischemic etiology 58% Diabetes 56% EF > 50% 26% Median or % shown; No significant between group differences

19 Results Dopamine Strategy

20 Low Dose Dopamine: Co-primary End-points 72 Hour Urine Volume Change in Cystatin-C

21 Low Dose Dopamine Sub-group Analysis

22 Low Dose Dopamine Secondary Endpoints No significant treatment effect on secondary endpoints reflective of: Decongestion Renal function Symptom relief Study Drug Tolerance Study drug reduced dose or d/c - Hypotension Study drug reduced dose or d/c - Tachycardia Study drug d/c before 72 hrs Any Cause Dopamine (n=122) Placebo (N = 119) P Value 0.9% 10.4% < % 0.9% < % 25% 0.72

23 Low Dose Dopamine Clinical Outcomes 60 Day Death/ Unscheduled office visit/ HF Readmission 180 Day Mortality

24 Results Nesiritide Strategy

25 Low Dose Nesiritide Sub-group Analysis

26 Low Dose Nesiritide Clinical Outcomes 60 Day Death/ Unscheduled office visit/ HF Readmission 180 Day Mortality

27 Conclusions In patients with AHF and underlying renal dysfunction, when added to standardized diuretic dosing, neither low dose dopamine, nor low dose nesiritide, enhanced decongestion or improved renal function..

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