Skip to main content
. 2022 Aug 25;2022(8):CD013751. doi: 10.1002/14651858.CD013751.pub2

Comparison 3. Hypoxia‐inducible factor (HIF) stabiliser versus erythropoiesis‐stimulating agent (ESA).

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
3.1 Cardiovascular death 17   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.1.1 Low‐dose HIF 6 981 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.14, 6.41]
3.1.2 Medium‐dose HIF 7 7442 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.88, 1.27]
3.1.3 High‐dose HIF 9 2067 Risk Ratio (M‐H, Random, 95% CI) 1.11 [0.31, 3.96]
3.1.4 Overall dose HIF 17 10340 Risk Ratio (M‐H, Random, 95% CI) 1.05 [0.88, 1.26]
3.2 Fatigue 2 3471 Risk Ratio (M‐H, Random, 95% CI) 0.80 [0.56, 1.16]
3.2.1 Medium‐dose HIF 2 3471 Risk Ratio (M‐H, Random, 95% CI) 0.80 [0.56, 1.16]
3.3 Death (any cause) 29   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.3.1 Low‐dose HIF 9 1295 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.33, 2.75]
3.3.2 Medium‐dose HIF 15 15586 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.88, 1.08]
3.3.3 High‐dose HIF 13 4745 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.63, 1.37]
3.3.4 Overall dose HIF 29 21370 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.91, 1.06]
3.4 Nonfatal myocardial infarction 7   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.4.1 Low‐dose HIF 2 148 Risk Ratio (M‐H, Random, 95% CI) Not estimable
3.4.2 Medium‐dose HIF 5 7153 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.72, 1.16]
3.4.3 High‐dose HIF 4 612 Risk Ratio (M‐H, Random, 95% CI) 1.90 [0.31, 11.54]
3.4.4 Overall dose HIF 7 7765 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.76, 1.10]
3.5 Fatal or nonfatal myocardial infarction (overall) 15   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.5.1 Low‐dose HIF 2 148 Risk Ratio (M‐H, Random, 95% CI) Not estimable
3.5.2 Medium‐dose HIF 9 10949 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.78, 1.10]
3.5.3 High‐dose HIF 8 3234 Risk Ratio (M‐H, Random, 95% CI) 1.22 [0.68, 2.19]
3.5.4 Overall dose HIF 15 14183 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.80, 1.12]
3.6 Nonfatal stroke 5   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.6.1 Low‐dose HIF 3 336 Risk Ratio (M‐H, Random, 95% CI) 4.78 [0.24, 96.68]
3.6.2 Medium‐dose HIF 3 6918 Risk Ratio (M‐H, Random, 95% CI) 1.07 [0.62, 1.83]
3.6.3 High‐dose HIF 1 115 Risk Ratio (M‐H, Random, 95% CI) Not estimable
3.6.4 Overall dose HIF 5 7285 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.71, 1.56]
3.7 Fatal or nonfatal stroke (overall) 7   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.7.1 Low‐dose HIF 4 398 Risk Ratio (M‐H, Random, 95% CI) 1.37 [0.11, 17.51]
3.7.2 Medium‐dose HIF 4 6980 Risk Ratio (M‐H, Random, 95% CI) 1.02 [0.70, 1.50]
3.7.3 High‐dose HIF 3 795 Risk Ratio (M‐H, Random, 95% CI) 0.49 [0.16, 1.53]
3.7.4 Overall dose HIF 7 8025 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.64, 1.40]
3.8 Nonfatal hospitalisation for heart failure 2 6836 Risk Ratio (M‐H, Random, 95% CI) 1.23 [1.00, 1.52]
3.8.1 Medium‐dose HIF 2 6836 Risk Ratio (M‐H, Random, 95% CI) 1.23 [1.00, 1.52]
3.9 Fatal or nonfatal hospitalisation for heart failure 3   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.9.1 Medium‐dose HIF 2 6836 Risk Ratio (M‐H, Random, 95% CI) 1.16 [0.98, 1.39]
3.9.2 High‐dose HIF 1 616 Risk Ratio (M‐H, Random, 95% CI) 1.03 [0.59, 1.79]
3.9.3 Overall dose HIF 3 7452 Risk Ratio (M‐H, Random, 95% CI) 1.15 [0.97, 1.36]
3.10 Peripheral arterial event 2   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.10.1 Low‐dose HIF 2 148 Risk Ratio (M‐H, Random, 95% CI) Not estimable
3.10.2 Medium‐dose HIF 2 144 Risk Ratio (M‐H, Random, 95% CI) Not estimable
3.10.3 High‐dose HIF 2 179 Risk Ratio (M‐H, Random, 95% CI) Not estimable
3.10.4 Overall dose HIF 2 323 Risk Ratio (M‐H, Random, 95% CI) Not estimable
3.11 Transfusion 11   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.11.1 Low‐dose HIF 3 192 Risk Ratio (M‐H, Random, 95% CI) 1.04 [0.23, 4.75]
3.11.2 Medium‐dose HIF 7 7343 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.81, 1.02]
3.11.3 High‐dose HIF 7 3443 Risk Ratio (M‐H, Random, 95% CI) 0.85 [0.62, 1.16]
3.11.4 Overall dose HIF 11 10786 Risk Ratio (M‐H, Random, 95% CI) 0.87 [0.76, 1.00]
3.12 Proportion reaching target haemoglobin 14   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.12.1 Low‐dose HIF 7 861 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.91, 1.10]
3.12.2 Medium‐dose HIF 4 507 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.69, 1.29]
3.12.3 High‐dose HIF 9 3425 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.91, 1.12]
3.12.4 Overall dose HIF 14 4601 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.93, 1.07]
3.13 Kidney failure 9   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.13.1 Low‐dose HIF 2 361 Risk Ratio (M‐H, Random, 95% CI) 1.14 [0.20, 6.43]
3.13.2 Medium‐dose HIF 7 6647 Risk Ratio (M‐H, Random, 95% CI) 1.03 [0.91, 1.16]
3.13.3 High‐dose HIF 2 368 Risk Ratio (M‐H, Random, 95% CI) 6.88 [0.89, 53.20]
3.13.4 Overall dose HIF 9 7312 Risk Ratio (M‐H, Random, 95% CI) 1.02 [0.91, 1.15]
3.14 Thrombosis 11   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.14.1 Medium‐dose HIF 7 14532 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.71, 1.37]
3.14.2 High‐dose HIF 4 2494 Risk Ratio (M‐H, Random, 95% CI) 1.35 [0.99, 1.83]
3.14.3 Overall dose HIF 11 17026 Risk Ratio (M‐H, Random, 95% CI) 1.09 [0.86, 1.39]
3.15 Loss of unassisted patency (occlusion/stenosis) 8   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.15.1 Low‐dose HIF 1 271 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.53, 1.69]
3.15.2 Medium‐dose HIF 3 800 Risk Ratio (M‐H, Random, 95% CI) 0.65 [0.29, 1.47]
3.15.3 High‐dose HIF 4 1874 Risk Ratio (M‐H, Random, 95% CI) 1.51 [0.99, 2.30]
3.15.4 Overall dose HIF 8 2945 Risk Ratio (M‐H, Random, 95% CI) 1.16 [0.85, 1.59]
3.16 Access intervention 1   Risk Ratio (M‐H, Random, 95% CI) Totals not selected
3.16.1 High‐dose HIF 1   Risk Ratio (M‐H, Random, 95% CI) Totals not selected
3.17 Cancer 7   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.17.1 Low‐dose HIF 2 515 Risk Ratio (M‐H, Random, 95% CI) 0.57 [0.10, 3.35]
3.17.2 Medium‐dose HIF 3 641 Risk Ratio (M‐H, Random, 95% CI) 0.65 [0.24, 1.74]
3.17.3 High‐dose HIF 2 531 Risk Ratio (M‐H, Random, 95% CI) 0.87 [0.13, 5.85]
3.17.4 Overall dose HIF 7 1687 Risk Ratio (M‐H, Random, 95% CI) 0.83 [0.43, 1.59]
3.18 Infection 1   Risk Ratio (M‐H, Random, 95% CI) Totals not selected
3.18.1 High‐dose HIF 1   Risk Ratio (M‐H, Random, 95% CI) Totals not selected
3.19 Hyperkalaemia 21   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.19.1 Low‐dose HIF 2 570 Risk Ratio (M‐H, Random, 95% CI) 1.72 [0.77, 3.85]
3.19.2 Medium‐dose HIF 10 15152 Risk Ratio (M‐H, Random, 95% CI) 0.90 [0.82, 1.00]
3.19.3 High‐dose HIF 9 4455 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.68, 1.50]
3.19.4 Overall dose HIF 21 20177 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.82, 1.04]
3.20 Pulmonary hypertension 7   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.20.1 Low‐dose HIF 2 570 Risk Ratio (M‐H, Random, 95% CI) 2.98 [0.12, 72.46]
3.20.2 Medium‐dose HIF 4 7455 Risk Ratio (M‐H, Random, 95% CI) 1.13 [0.51, 2.47]
3.20.3 High‐dose HIF 1 616 Risk Ratio (M‐H, Random, 95% CI) 0.30 [0.03, 2.89]
3.20.4 Overall dose HIF 7 8641 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.56, 2.01]
3.21 Diabetic retinopathy 8   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
3.21.1 Low‐dose HIF 1 299 Risk Ratio (M‐H, Random, 95% CI) 2.01 [0.18, 21.97]
3.21.2 Medium‐dose HIF 6 4435 Risk Ratio (M‐H, Random, 95% CI) 1.18 [0.65, 2.15]
3.21.3 High‐dose HIF 1 302 Risk Ratio (M‐H, Random, 95% CI) 3.04 [0.12, 74.03]
3.21.4 Overall dose HIF 8 5036 Risk Ratio (M‐H, Random, 95% CI) 1.26 [0.71, 2.22]