Short‐acting erythropoiesis‐stimulating agents for anaemia in predialysis patients

Deirdre Hahn; Christopher I Esezobor; Noha Elserafy; Angela C Webster; Elisabeth M Hodson

doi:10.1002/14651858.CD011690.pub2

Scolaris Content Display Scolaris Content Display

Topics

Figure 1

Study flow diagram.

Navigate to figure in ReviewOpen in new tab

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Navigate to figure in ReviewOpen in new tab

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Navigate to figure in ReviewOpen in new tab

Analysis 1.1

Comparison 1 Epoetin alpha every 2 weeks versus weekly, Outcome 1 Change in haemoglobin level.

Navigate to figure in ReviewOpen in new tab

Analysis 1.2

Comparison 1 Epoetin alpha every 2 weeks versus weekly, Outcome 2 Number reaching target haemoglobin.

Navigate to figure in ReviewOpen in new tab

Analysis 1.3

Comparison 1 Epoetin alpha every 2 weeks versus weekly, Outcome 3 Number of deaths.

Navigate to figure in ReviewOpen in new tab

Analysis 1.4

Comparison 1 Epoetin alpha every 2 weeks versus weekly, Outcome 4 Adverse events.

Navigate to figure in ReviewOpen in new tab

Analysis 2.1

Comparison 2 Epoetin alpha every 4 weeks versus every 2 weeks, Outcome 1 Change in haemoglobin level.

Navigate to figure in ReviewOpen in new tab

Analysis 2.2

Comparison 2 Epoetin alpha every 4 weeks versus every 2 weeks, Outcome 2 Number reaching target haemoglobin.

Navigate to figure in ReviewOpen in new tab

Analysis 2.3

Comparison 2 Epoetin alpha every 4 weeks versus every 2 weeks, Outcome 3 Number of deaths.

Navigate to figure in ReviewOpen in new tab

Analysis 2.4

Comparison 2 Epoetin alpha every 4 weeks versus every 2 weeks, Outcome 4 Adverse events.

Navigate to figure in ReviewOpen in new tab

Analysis 3.1

Comparison 3 Epoetin alpha different doses given three times weekly, Outcome 1 Final haemoglobin.

Navigate to figure in ReviewOpen in new tab

Analysis 3.2

Comparison 3 Epoetin alpha different doses given three times weekly, Outcome 2 Mean arterial BP.

Navigate to figure in ReviewOpen in new tab

Analysis 3.3

Comparison 3 Epoetin alpha different doses given three times weekly, Outcome 3 Final creatinine levels.

Navigate to figure in ReviewOpen in new tab

Analysis 4.1

Comparison 4 Epoetin alpha different doses given every four weeks, Outcome 1 Final haemoglobin.

Navigate to figure in ReviewOpen in new tab

Analysis 4.2

Comparison 4 Epoetin alpha different doses given every four weeks, Outcome 2 Number reaching target haemoglobin.

Navigate to figure in ReviewOpen in new tab

Analysis 4.3

Comparison 4 Epoetin alpha different doses given every four weeks, Outcome 3 Number of deaths.

Navigate to figure in ReviewOpen in new tab

Analysis 4.4

Comparison 4 Epoetin alpha different doses given every four weeks, Outcome 4 Adverse events.

Navigate to figure in ReviewOpen in new tab

Analysis 5.1

Comparison 5 Epoetin alpha IV versus subcutaneous administration, Outcome 1 Final haemoglobin.

Navigate to figure in ReviewOpen in new tab

Analysis 6.1

Comparison 6 Epoetin theta versus epoetin beta, Outcome 1 Final Hb.

Navigate to figure in ReviewOpen in new tab

Analysis 6.2

Comparison 6 Epoetin theta versus epoetin beta, Outcome 2 Mean weekly epoetin dose.

Navigate to figure in ReviewOpen in new tab

Analysis 6.3

Comparison 6 Epoetin theta versus epoetin beta, Outcome 3 Deaths.

Navigate to figure in ReviewOpen in new tab

Analysis 6.4

Comparison 6 Epoetin theta versus epoetin beta, Outcome 4 Adverse events.

Navigate to figure in ReviewOpen in new tab

Summary of findings for the main comparison. Epoetin alpha every 2 weeks versus to weekly for anaemia in CKD patients not receiving dialysis

Epoetin alpha every 2 weeks versus to weekly for anaemia in CKD patients not receiving dialysis
Patient or population: anaemia in predialysis patients Intervention: epoetin alpha every 2 weeks Comparison: weekly
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with weekly	Risk with Epoetin alpha every 2 weeks
Change in Hb level	The mean change in Hb level was 0 g/dL	The mean change in Hb level in the intervention group was 0.19 g/dL lower (0.32 g/dL lower to 0.06 g/dL lower)	‐	798 (4)	⊕⊕⊝⊝ LOW ^{1 2}	downgraded for study limitations and indirectness
Number reaching target Hb	Study population		RR 0.96 (0.93 to 0.99)	798 (4)	⊕⊕⊝⊝ LOW ^{1 2}	downgraded for study limitations and indirectness
	960 per 1000	922 per 1000 (893 to 951)
	Moderate
	947 per 1000	910 per 1000 (881 to 938)
Number of deaths	Study population		RR 0.89 (0.38 to 2.07)	838 (4)	⊕⊕⊝⊝ LOW ^{1 3}	downgraded for study limitations and imprecision
	28 per 1000	24 per 1000 (10 to 57)
	Moderate
	22 per 1000	20 per 1000 (9 to 46)
Adverse events: RBC transfusions	Study population		RR 1.56 (0.71 to 3.45)	580 (3)	⊕⊕⊝⊝ LOW ^{3 4}	downgraded for imprecision and study limitations
	33 per 1000	52 per 1000 (23 to 114)
	Moderate
	37 per 1000	58 per 1000 (26 to 128)
Adverse events: hypertension	Study population		RR 0.85 (0.55 to 1.32)	838 (4)	⊕⊕⊕⊝ MODERATE ¹	downgraded for study limitations
	100 per 1000	85 per 1000 (55 to 132)
	Moderate
	95 per 1000	81 per 1000 (52 to 126)
Adverse events: thrombovascular events	Study population		RR 1.41 (0.67 to 3.00)	838 (4)	⊕⊕⊝⊝ LOW ^{1 3}	downgraded for study limitations and imprecision
	28 per 1000	39 per 1000 (18 to 83)
	Moderate
	27 per 1000	38 per 1000 (18 to 80)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; Hb: haemoglobin; RBC: red blood cells
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ allocation concealment unclear in 3 of 4 studies ² surrogate outcome ³ few studies with low numbers and wide confidence ⁴ allocation concealment unclear in 2 of 3 studies

Summary of findings for the main comparison. Epoetin alpha every 2 weeks versus to weekly for anaemia in CKD patients not receiving dialysis

Navigate to table in Review

Summary of findings 2. Epoetin alfa every four weeks versus with every two weeks in CKD patients not receiving dialysis

Epoetin alfa every four weeks versus with every two weeks in CKD patients not receiving dialysis
Patient or population: anaemia in predialysis patients Intervention: epoetin alpha every 4 weeks Comparison: every 2 weeks
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with every 2 weeks	Risk with Epoetin alpha every 4 weeks
Change in Hb level	The mean change in Hb level was 0	The mean change in Hb level in the intervention group was 0.15g/dL lower (0.41 g/dL lower to 0.1g/dL more)	‐	671 (3)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}	downgraded for study limitations, heterogeneity and indirectness
Number reaching target Hb	Study population		RR 0.95 (0.84 to 1.07)	687 (3)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}	downgraded for study limitations, heterogeneity and indirectness
	916 per 1000	870 per 1000 (769 to 980)
	Moderate
	895 per 1000	850 per 1000 (752 to 957)
Number of deaths	Study population		RR 0.95 (0.33 to 2.75)	724 (3)	⊕⊕⊝⊝ LOW ^{1 4}	downgraded for study limitations, imprecision
	22 per 1000	21 per 1000 (7 to 62)
	Moderate
	26 per 1000	25 per 1000 (9 to 72)
Adverse events: RBC transfusions	Study population		RR 1.26 (0.53 to 2.98)	470 (2)	⊕⊕⊝⊝ LOW ^{1 4}	downgraded for study limitations, imprecision
	38 per 1000	48 per 1000 (20 to 114)
	Moderate
	35 per 1000	44 per 1000 (18 to 103)
Adverse events: hypertension	Study population		RR 1.02 (0.62 to 1.69)	724 (3)	⊕⊕⊕⊝ MODERATE ¹	downgraded for study limitations
	70 per 1000	72 per 1000 (44 to 119)
	Moderate
	62 per 1000	63 per 1000 (38 to 104)
Adverse events: arteriovenous complications	Study population		RR 1.02 (0.39 to 2.68)	724 (3)	⊕⊕⊝⊝ LOW ^{1 4}	downgraded for study limitations, imprecision
	26 per 1000	26 per 1000 (10 to 68)
	Moderate
	23 per 1000	24 per 1000 (9 to 62)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; Hb: haemoglobin; RBC: red blood cells
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ two of the three studies had unclear allocation concealment ² surrogate outcome ³ unexplained heterogeneity ⁴ small numbers with wide confidence intervals

Summary of findings 2. Epoetin alfa every four weeks versus with every two weeks in CKD patients not receiving dialysis

Navigate to table in Review

Summary of findings 3. Epoetin theta versus epoetin beta in CKD patients not receiving dialysis

Epoetin theta versus epoetin beta in CKD patients not receiving dialysis
Patient or population: anaemia in predialysis patients Intervention: epoetin theta Comparison: epoetin beta
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with epoetin beta	Risk with Epoetin theta
Final Hb	The mean final Hb was 0 g/dL	The mean final Hb in the intervention group was 0.02 g/dL lower (0.25 g/dL lower to 0.21 g/dL higher)	‐	288 (1)	⊕⊕⊕⊝ MODERATE ¹	downgraded for indirectness ‐ surrogate outcomes
Mean weekly epoetin dose	The mean weekly epoetin dose was 0 units/week	The mean weekly epoetin dose in the intervention group was 0.4 units per week higher (5.68 units per week lower 6.48 units/week higher)	‐	288 (1)	⊕⊕⊝⊝ LOW ^{1 2}	downgraded for indirectness ‐ surrogate outcomes and imprecision
Deaths	Study population		RR 2.46 (0.29 to 20.77)	288 (1)	⊕⊕⊝⊝ LOW ²	downgraded for imprecision
	11 per 1000	26 per 1000 (3 to 219)
	Moderate
	11 per 1000	26 per 1000 (3 to 218)
Adverse events: hypertension	Study population		RR 0.35 (0.11 to 1.08)	288 (1)	⊕⊕⊕⊝ MODERATE ²	downgraded for imprecision
	74 per 1000	26 per 1000 (8 to 80)
	Moderate
	74 per 1000	26 per 1000 (8 to 80)
Adverse events: RBC transfusions	Study population		RR 1.48 (0.06 to 36.10)	288 (1)	⊕⊕⊝⊝ LOW ²	downgraded for imprecision
	0 per 1000	0 per 1000 (0 to 0)
Adverse events: discontinuation of therapy	Study population		RR 1.77 (0.68 to 4.63)	288 (1)	⊕⊕⊝⊝ LOW ²	downgraded for imprecision
	53 per 1000	93 per 1000 (36 to 244)
	Moderate
	53 per 1000	93 per 1000 (36 to 244)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; RBC: red blood cells
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Surrogate outcome, not a patient‐centred outcome ² Small numbers, wide confidence intervals

Summary of findings 3. Epoetin theta versus epoetin beta in CKD patients not receiving dialysis

Navigate to table in Review

Comparison 1. Epoetin alpha every 2 weeks versus weekly

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in haemoglobin level Show forest plot	4	785	Mean Difference (IV, Random, 95% CI)	‐0.20 [‐0.33, ‐0.07]

2 Number reaching target haemoglobin Show forest plot	4	798	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.93, 0.99]

3 Number of deaths Show forest plot	4	838	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.38, 2.07]

4 Adverse events Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 RBC transfusions	3	580	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.71, 3.45]
4.2 Hypertension	4	838	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.55, 1.32]
4.3 Thrombovascular events	4	838	Risk Ratio (M‐H, Random, 95% CI)	1.41 [0.67, 3.00]
4.4 Adverse events leading to discontinuation of therapy	1	258	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.20, 4.79]

Comparison 1. Epoetin alpha every 2 weeks versus weekly

Navigate to table in Review

Comparison 2. Epoetin alpha every 4 weeks versus every 2 weeks

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in haemoglobin level Show forest plot	3	671	Mean Difference (IV, Random, 95% CI)	‐0.16 [‐0.43, 0.10]

2 Number reaching target haemoglobin Show forest plot	3	687	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.84, 1.07]

3 Number of deaths Show forest plot	3	724	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.33, 2.75]

4 Adverse events Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 RBC transfusions	2	470	Risk Ratio (M‐H, Random, 95% CI)	1.26 [0.53, 2.98]
4.2 Hypertension	3	724	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.62, 1.69]
4.3 Arteriovenous complications	3	724	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.39, 2.68]

Comparison 2. Epoetin alpha every 4 weeks versus every 2 weeks

Navigate to table in Review

Comparison 3. Epoetin alpha different doses given three times weekly

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Final haemoglobin Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

1.1 100 U/kg versus 50 U/kg	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 150 U/kg versus 50 U/kg	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
2 Mean arterial BP Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

2.1 100 IU/kg/wk versus 50 IU/kg/wk	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 150 IU/kg/wk versus 50 IU/kg/wk	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3 Final creatinine levels Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

3.1 100 IU/kg/wk versus 50 IU/kg/wk	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 150 IU/kg/wk versus 50 IU/kg/wk	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 3. Epoetin alpha different doses given three times weekly

Navigate to table in Review

Comparison 4. Epoetin alpha different doses given every four weeks

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Final haemoglobin Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

2 Number reaching target haemoglobin Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

3 Number of deaths Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

4 Adverse events Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

4.1 Hypertension	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Thrombovascular events	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.3 RBC transfusions	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 4. Epoetin alpha different doses given every four weeks

Navigate to table in Review

Comparison 5. Epoetin alpha IV versus subcutaneous administration

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Final haemoglobin Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 5. Epoetin alpha IV versus subcutaneous administration

Navigate to table in Review

Comparison 6. Epoetin theta versus epoetin beta

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Final Hb Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

2 Mean weekly epoetin dose Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

3 Deaths Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

4 Adverse events Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

4.1 Hypertension	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 RBC transfusions	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.3 Discontinuation of therapy	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 6. Epoetin theta versus epoetin beta

Navigate to table in Review

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Cochrane Review language

Website language

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet

Scolaris Content Display Scolaris Content Display

Topics

Scolaris Language Selector Scolaris Language Selector

Scolaris Content Display Scolaris Content Display

Previously accessed institutions

Scolaris Content Display Scolaris Content Display

Institutional users

Previously accessed institutions

Other access options

	Cochrane Review language Select your preferred language for Cochrane Reviews and other content. Sections without translation will be in English.

	Website language Select your preferred language for the Cochrane Library website.

Cochrane Review language

Website language

Related content

Related reviews and protocols

Cochrane Clinical Answers

Topics

Copy or download citation

Cochrane Review language

Website language

Previously accessed institutions

Institutional users

Previously accessed institutions

Other access options