Table 1.
Effects of subcutaneous titrated dosages of erythropoietin on cardiovascular endpoints in patients with CKD not on dialysis
| Reference (study design) | Level of renal function; study duration | No. of pts | Treatment regimen | Endpoint | Outcome |
| Left ventricular hypertrophy | |||||
| Ayus et al. [54] (uncontrolled) | CrCl 10–30 mL/min (diabetic) or 20–40 mL/min (nondiabetic); 6 mo | 40 (Hb <10 g/dL) | EPO to 12 g/dL | Change-from-baseline LVMI | In anemic pts, LVMI decreased vs baseline (142 vs 157 g/m2;P = 0.007) as Hb increased from 9.1 to 11.3 g/dL (P = 0.001). |
| 61 (Hb>10 g/dL) | Standard care | ||||
| CREATE study [61] (r) | GFR 15–35 mL/min/1.73 m2, Hb 11.0–12.5 g/dL;3 yrs | 300 | EPO to 13–15 g/dL | Composite of 8 cardiovascular events (primary), LVMI (secondary) | Baseline LVMI: high-Hb group, 120.3 ± 35.0 g/m2 low-Hb group, 118.0 ± 34.3 g/m2 Change at year 1: High-Hb group, -4.6 g/m2 Low-Hb group, -3.3 g/m2; P = 0.59 Change at year 2 High-Hb group, -6.4 g/m2 Low-Hb group, -7.8 g/m2 |
| 300 | EPO to 10.5–11.5 g/dL | ||||
| Levin et al. [56] (r) | 24 mo | 78 | Early EPO to Hb 12–14 g/dL | Mean change-from-baseline LVMI | Mean LVMI change from baseline: early EPO, +0.37 g/m2 deferred EPO, +5.21 g/m2 |
| 58 | Deferred EPO to 9.0–10.5 g/dL | ||||
| Roger et al. [57] (r, mc, uncontrolled) | CrCl 15–50 mL/min, Hb 11.0–12.0 g/dL (in women) and 11–13 g/dL (in men);2 yr or until dialysis | 75 | EPO to Hb 12–13 g/dL | Mean change-from baseline LVMI | No statistically significant between group changes in LVMI over 2 years. Based on per-protocol Hb levels: Change from baseline LVMI: Low Hb group +14 g/m2 High Hb group -1 g/m2. |
| 80 | EPO to Hb 9–10 g/dL | ||||
| Congestive heart failure | |||||
| Mancini et al. [77] (r) | SrCr<2.5 mg/dL, NYHA functional class III-IV, Hct<35%;3 mo | 15 | EPO 15 000–30 000/wk | Blood and exercise parameters | Changes from baseline: EPO group: Peak VO2 11.0 to 12.7 mL·min-1·kg-1, P < .05 Exercise duration 590 to 657s, P < 0.004 Placebo group: no significant changes |
| 8 | Placebo | ||||
| Silverberg et al. [45] (retrospective) | Mean NYHA 3.66, SrCr 2.6 mg/dL, Hct 30%, Hb 10 g/dL;>6 mo |
26 | EPO + IV iron to Hb 12 g/dL | NYHA functional status, LVEF, healthcare utilization | Changes from baseline: Functional status 3.7 to 2.7, P < 0.05 LVEF 28% to 35%, P < 0.001 No. of hospitalizations/pt 2.7 to 0.2, P < 0.05). |
| Silverberg et al. [47] (r) | NYHA class III-IV, LVEF ≤40%, Hb 10–11.5 g/dL, 50% with CKD; 8.2 mo | 16 | EPO + IV iron to Hb ≥12.5 g/dL | NYHA functional status, LVEF, furosemide requirements, healthcare utilization | Changes from baseline: EPO + iron group: NYHA class, 42.1% improvement LVEF: +5.5% Length of hospitalization: -79% Standard care group: NYHA class: 11% worsening LVEF: -5% Length of hospitalization: +58% |
| 16 | Standard care | ||||
| Silverberg et al. [46] (nr) | NIDDM or no NIDDM plus severe CHF, GFR decline >1 mL/min/mo; 11.8 mo | 84 (NIDDM) | EPO to Hb 12.5 g/dL + IV iron PRN | NYHA functional class; VAS for fatigue and breathlessness; LVEF | Changes from baseline: NIDDM pts: NYHA functional class 35% improvement LVEF +7% non-NIDDM pts: NYHA functional class: 32% improvement LVEF +12% No statistically significant differences between NIDDM and non-NIDDM. |
| 95 (no NIDDM) | |||||
| Silverberg et al. [78] (nc) | Symptomatic CHF despite optimal therapies, Hb<12 g/dL,91% had CKD (CrCl <60 mL/Min);20.7 mo | 78 | EPO + PRN IV iron to Hb 13 g/dL | NYHA functional class, LVEF, healthcare utilization | Changes from baseline: (all P < 0.01). NYHA class 2.5 (vs 3.7), LVEF 37% (vs 33%); No. of hospitalizations 0.7/year (vs 2.7/year) |
CrCl = creatinine clearance; db = double-blind; EPO = epoetin; GFR = glomerular filtration rate; Hct = hematocrit; IV = intravenous; LOHS = length of hospital stay; LVEF = left ventricular ejection fraction; LVMI = left ventricular mass index; mc = multicenter; mo = months; nc = noncomparative; NYHA = New York Heart Association; PLA = placebo; PRN = as required; pts = patients; r = randomized; SrCr = serum creatinine; VAS = visual-analog scale; wk = week.