Role of Anaemia – from CRS to CRAS

CRAS definition and epidemiology

The First Definition of CRAS

Silverberg proposed the term Cardio-Renal Anaemia Syndrome (CRAS) 10 years ago to reflect that there is an interaction between

renal failure, heart failure and anaemia

Silverberg D et al. Eur J Heart Fail 2002;4(6):681–686

Anaemia

Heartfailure

Renalfailure

The Definition of CRAS Differs Depending on your Viewpoint (1)

Nephrologists

CKDAny degree of

anaemiaAny degree of heart failure

CKD Severe anaemiaSevere

heart failure

Renal failure Severe anaemia Cardiovascular events

Renal failure AnaemiaCardiovascular

disease

CKD Anaemia CHF

The Definition of CRAS Differs Depending on your Viewpoint (2)

Cardiologists

CHFAny degree of

anaemiaAny degree of

renal insufficiency

CHF Severe anaemia Renal failure

Cardiovascular disease

Severe anaemia Renal failure

Cardiovascular disease

Anaemia Renal insufficiency

CHF Anaemia CKD

A Definition of CRAS for 2010

CRAS is a pathophysiological process involving the progressive deterioration of heart and kidney function linked with worsening anaemia

– CRAS is a vicious cycle where worsening of one factor negatively impacts on the other two conditions and itself, resulting in progressive deterioration

CRAS is a combination of heart failure, kidney failure and anaemia

What defines the above factors?

Any degree of heart failure

Any degree of anaemia

Any degree of kidney failure

The Prevalence of CRAS is Dependant upon your Definition of CKD, CHF and of Anaemia

CHF CKD

Anaemia

Anaemia +

CKD

Anaemia +

CHF

CRAS

CHF + CKD

A total of 9,971 patients had a value for Hb reported that was ≤11 g/dL in 18% of men and 23% of women

Cleland JG et al. Eur Heart J 2003;24:442–463

N=5249 men

33% with Hb <12 g/dL

Nu

mb

er

of

pati

en

ts

Hb (g/dL)

500

400

300

200

100

04–4.4

5–5.46–6.4

7–7.4

8–8.4

9–9.4

10–10.4

11–11.4

12–12.4

13–13.4

14–14.4

15–15.4

16–16.4

17–17.4

18–18.4

19–19.4

20–20.4

Hb levels in the EuroHeart Failure Survey Programme

CRAS in US and European HF Surveys

Galvao M et al. J Card Fail 2006;12:100–107; Nieminen MS et al. Eur J Heart Fail 2008;10:140–148

60

50

40

30

20

10

0ADHERE 105,000 patients EuroHF Survey II

Renal failure Anaemia

Pati

en

ts (

%)

Prevalence Data for CRAS are Varied

Anaemia is common in patients with heart failure (HF) –prevalence ranges from 4–55%1

In patients with CHF NYHA functional class IV, the prevalence of anaemia when defined as <12g/dL and ≤11g/dL was 79.1%3 and 14.4%, respectively4

The prevalence of renal impairment plus anaemia (≤11g/dL) in New York heart association (NYHA) functional class IV HF patients is 6.3%4

The prevalence of chronic renal insufficiency (CRI) in new onset HF patients is 8.8%2 and the prevalence of renal insufficiency in acutely decompensated HF patients is 30%5

The prevalence of CHF in endstage renal disease is 63.7%6

1. Lang C & Mancini D. Heart 2007;93:665–671; 2. Ezekowitz J et al. Circulation 2003;107:223–225; 3. Silverberg D et al. J Am Coll Cardiol 2000;35:1737–1744; 4. Cromie N et al. Heart 2002;87:377–378;

5. Fonarow G et al. JAMA 2005;293:572–580; 6. Avorn J et al. Arch Intern Med 2002;162:2002–2006

New-onset HF Patients with both CKD and Anaemia

Population-based cohort of 12,065 patients with new-onset CHF

– Database analysis from 138 acute-care Canadian hospitals

– April 1993–March 2001

– Analysis of prevalence and cause of anaemia

Adapted from Ezekowitz J et al. Circulation 2003;107:223–225

14%3%

6%

77%

CHF + anaemia alone (n=1,696)

CHF + anaemia + CKD (n=387)

CHF + CKD alone (n=674)

CHF alone (n=9,308)

HF, CKD and Anaemia Occur Frequently in the Same Patient

Prospective, single-centre, observational study2

– 955 consecutive patients with HF (LVEF <45%)

– Median follow-up 531 days

– Investigation of the presence of anaemia, and its cause

Adapted from de Silva R et al. Am J Cardiol 2006;98:391–398

CHF + anaemia* alone (n=94)CHF + anaemia* + CKD** (n=211)CHF + CKD** alone (n=307)CHF alone (n=343)

LVEF, left ventricular ejection fraction*Hb <12 g/dL in women, <13 g/dL in men; **eGFR <60 mL/min/1.73 m2

10%

22%

32%

36%

CHF + anaemia* alone (n=304)

CHF + anaemia* + CKD** (n=373)

CHF + CKD** alone (n=583)

CHF alone (n=1393)

14%

11.5%

22%

52.5%

Multivariable analysis of data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program

– 2,653 patients with NYHA class II–IV

Prevalence of CRAS may be Greater than Current Estimates

“…about half the patients admitted to hospital with a primary diagnosis of CHF…have anaemia…and the great majority will also have CKI (chronic kidney insufficiency)”1

Silverberg et al. noted the majority of CKI patients with anaemia also had CHF2

1. Silverberg DS et al. Semin Nephrol 2006;26:296; 2. Silverberg D et al. Nephrol Dial Transplant 2003;18(suppl 8):viii7–viii12

Prevalence Data for CRAS are Limited

Very few studies have specifically assessed the prevalence of CRAS within the CKD and CHF populations

Exclusion criteria for clinical trials often remove patients with CRAS and so a true prevalence of the disorder is unknown