Table 1 Effects of subcutaneous titrated dosages of erythropoietin on cardiovascular endpoints in patients with CKD not on dialysis

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)