Summary of findings 1. Hypoxia‐inducible factor (HIF) stabilisers versus placebo for people with chronic kidney disease (CKD).
| HIF stabilisers versus placebo for people with CKD | ||||||
|
Patient or population: people with CKD (including HD and PD) Settings: multinational Intervention: HIF stabilisers Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No. of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | HIF stabilisers | |||||
|
Cardiovascular death Median follow‐up: 16 weeks |
Low risk population (CKD) |
RR 3.68 (0.19 to 70.21) |
1114 (10) | ⊕⊝⊝⊝ very low1,2,3 | Studies were not designed to measure effects of HIF stabiliser management of anaemia on CV death compared with placebo in CKD and HD | |
| No events | 3/607** | |||||
| High risk population (HD) | ||||||
| No events | No events | |||||
| Fatigue | Not reported | Not reported | ‐‐ | ‐‐ | ‐‐ | No studies reported this outcome |
| Life participation | Not reported | Not reported | ‐‐ | ‐‐ | ‐‐ | No studies reported this outcome |
|
Nonfatal myocardial infarction Median follow‐up: 24 weeks |
Low risk population (CKD) |
RR 1.29 (0.31 to 5.36) |
822 (3) | ⊕⊝⊝⊝ very low1,2,4 | The effects of HIF stabiliser management of anaemia on nonfatal MI were uncertain compared with placebo in CKD | |
| 8 per 1000 |
2 more per 1000 (from 6 fewer to 35 more) |
|||||
|
Nonfatal stroke Median follow‐up: 21 weeks |
Low risk population (CKD) | Not estimable | 228 (2) | ⊕⊝⊝⊝ very low1,2,4 | Studies were not designed to measure effects of HIF stabiliser management of anaemia on nonfatal stroke compared with placebo in CKD | |
| No events | No events | |||||
|
Proportion of patients requiring blood transfusion Median follow‐up: 18 weeks |
Low risk population (CKD) | RR 0.51 (0.44 to 0.60) | 4329 (8) | ⊕⊕⊕⊝ moderate1 | HIF stabiliser management of anaemia probably decreases the proportion of patients requiring blood transfusion compared to placebo in CKD and HD | |
| 200 per 1000 | 96 fewer per 1000 (from 112 fewer to 80 fewer) | |||||
| High risk population (HD) | ||||||
| 214 per 1000 | 169 fewer per 1000 (206 fewer to 30 more) | |||||
|
Proportion reaching target haemoglobin Median follow‐up: 16 weeks |
Low risk population (CKD) | RR 8.36 (6.42 to 10.89) | 5102 (10) | ⊕⊕⊕⊝ moderate1 | HIF stabiliser management of anaemia probably increases the proportion of patients reaching their Hb target compared to placebo in CKD and HD | |
| 83 per 1000 | 594 more per 1000 (424 more to 821 more) | |||||
| High risk population (CKD and HD) | ||||||
| No events | 63/141** | |||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ** Event rate derived from the raw data. A 'per thousand' rate is non‐informative in view of the scarcity of evidence and zero events in the control group HD: haemodialysis; PD: peritoneal dialysis; CI: confidence interval; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
1 Evidence certainty was downgraded by one level due to study limitations. Some studies had unclear risks for sequence generation and/or allocation concealment and the majority or all of them were not blinded (participant/investigator and/or outcomes assessor). All studies reported sources of funding
2 Evidence certainty was downgraded by one level due to imprecision
3 Evidence certainty was downgraded by one level due to indirectness in the study population
4 Evidence certainty was downgraded by one level due to imprecision (optimal information size was not met and the included studies reported zero events)