Role of Anaemia – from CRS to CRAS CRAS definition and epidemiology 1

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

The Definition of CRAS Differs Depending on your Viewpoint (1) Nephrologists CKD Anaemia CHF CKD Any degree of anaemia Any degree of heart failure CKD Severe anaemia Severe heart failure Renal failure Severe anaemia Cardiovascular events Renal failure Anaemia Cardiovascular disease 3

The Definition of CRAS Differs Depending on your Viewpoint (2) Cardiologists CHF Anaemia CKD CHF Any degree of anaemia Any degree of renal insufficiency CHF Severe anaemia Renal failure Cardiovascular disease Severe anaemia Renal failure Cardiovascular disease Anaemia Renal insufficiency 4

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 Any degree of heart failure Any degree of anaemia Any degree of kidney failure What defines the above factors? 5

The Prevalence of CRAS is Dependant upon your Definition of CKD, CHF and of Anaemia CHF + CKD Anaemia CRAS Anaemia + CHF Anaemia + CKD 6

Hb levels in the EuroHeart Failure Survey Programme 500 400 N=5249 men 33% with Hb <12 g/dL 300 Number of patients 200 100 4–4.4 5–5.4 6–6.4 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 (g/dL) 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 7

CRAS in US and European HF Surveys 60 50 40 Patients (%) 30 20 10 ADHERE 105,000 patients EuroHF Survey II Renal failure Anaemia Galvao M et al. J Card Fail 2006;12:100–107; Nieminen MS et al. Eur J Heart Fail 2008;10:140–148 8

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 9

New-onset HF Patients with both CKD and Anaemia 14% 3% 6% 77% 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 CHF + anaemia alone (n=1,696) CHF + anaemia + CKD (n=387) CHF + CKD alone (n=674) CHF alone (n=9,308) Adapted from Ezekowitz J et al. Circulation 2003;107:223–225 10

HF, CKD and Anaemia Occur Frequently in the Same Patient 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 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 10% 22% 32% 36% 14% 11.5% 22% 52.5% CHF + anaemia* alone (n=304) CHF + anaemia* + CKD** (n=373) CHF + CKD** alone (n=583) CHF alone (n=1393) 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 Adapted from de Silva R et al. Am J Cardiol 2006;98:391–398 11

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 12

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 13