Table 4.
Metaregression and subgroup analysis of sources of variability for major outcomes analysed in review (in respect of categorical and continuous study factors) in studies of angiotensin converting enzyme inhibitors compared with placebo
|
Mortality
|
Doubling of serum creatinine concentration
|
End stage renal disease
|
Microalbuminuria to macroalbuminuria
|
Microalbuminuria to normoalbuminuria
|
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Variable | Relative risk (95% CI): No of trials | P value | Relative risk (95% CI) | P value | Relative risk 95% CI); No of trials | P value | Relative risk (95% CI); No of trials | P value | Relative risk (95% CI); No of trials | P value |
| Type of diabetes: | ||||||||||
| 1
|
0.71 (0.33 to 1.52); n=4
|
0.84* | 0.57 (0.38 to 0.88); n=3
|
0.04* | 0.60 (0.36 to 1.01); n=2
|
0.56* | 0.44 (0.27 to 0.70); n=9
|
0.12* | 3.62 (2.24 to 5.83); n=10
|
<0.001* |
| 2
|
4.23 (0.69 to 25.83); n=2
|
0.21 (0.06 to 0.66); n=2
|
Not estimable
|
0.20 (0.08 to 0.52); n=3
|
24.53 (1.49 to 403.6); n=1
|
|||||
| Mixed | 0.54 (0.12 to 2.36); n=2 | 1.23 (0.67 to 2.30); n=1 | 0.88 (0.27 to 2.88); n=1 | Not estimable | 2.04 (0.41 to 10.11); n=2 | |||||
| Hypertension: | ||||||||||
| Present
|
0.80 (0.48 to 1.32); n=6
|
0.45 | 0.72 (0.43 to 1.23); n=4
|
0.22 | 0.67 (0.41 to 1.08); n=1
|
0.34 | 0.84 (0.67 to 1.05); n=4
|
0.001 | 2.12 (1.12 to 4.02); n=5
|
0.01 |
| Absent | 1.73 (0.22 to 13.44); n=2 | 0.32 (0.07 to 1.58); n=2 | 0.66 (0.41 to 1.07); n=2 | 0.37 (0.21 to 0.65); n=9 | 4.99 (2.52 to 9.89); n=7 | |||||
| Stage of nephropathy:
|
|
|
|
|
|
|
|
|
|
|
| Microalbuminuria
|
0.79 (0.53 to 1.16); n=4
|
0.92 | 0.52 (0.14 to 1.98); n=3
|
0.88 | 0.88 (0.27 to 2.88); n=1
|
0.55 | 0.47 (0.28 to 0.79); n=12
|
0.86 | 3.35 (1.83 to 6.16); n=12
|
0.80 |
| Macroalbuminuria
|
1.07 (0.37 to 3.12); n=4
|
0.56 (0.37 to 0.86); n=3
|
0.60 (0.36 to 1.01); n=2
|
0.24 (0.06 to 1.00); n=1
|
Not estimable
|
|||||
| Mixed | Not estimable | Not estimable | Not estimable | 0.41 (0.11 to 1.54); n=1 | 3.94 (1.48 to 10.48); n=1 | |||||
| Allocation concealment:
|
|
|
|
|
|
|
|
|
|
|
| Adequate
|
0.78 (0.61 to 1.00); n=1
|
0.88 | 1.11 (0.62 to 1.98); n=2
|
0.03 | 0.88 (0.27 to 2.88); n=1
|
0.55 | 0.83 (0.67 to 1.04); n=5
|
<0.001 | 2.71 (1.20 to 1.07); n=5
|
0.21 |
| Unclear | 0.98 (0.41 to 2.33); n=7 | 0.48 (0.29 to 0.80); n=4 | 0.60 (0.36 to 1.01); n=2 | 0.31 (0.18 to 0.52); n=9 | 3.72 (2.06 to 6.73); n=8 | |||||
| Blinding of participants or investigators:
|
|
|
|
|
|
|
|
|
|
|
| Yes
|
1.70 (0.22 to 13.18); n=2
|
0.46 | 0.32 (0.66 to 1.58); n=2
|
0.22 | 0.16 (0.00 to 2.88); n=1
|
0.34 | 0.27 (0.12 to 0.62); n=4
|
0.06 | 6.24 (1.96 to 19.85); n=3
|
0.21 |
| No | 0.79 (0.48 to 1.32); n=6 | 0.72 (0.43 to 1.23); n=4 | 0.67 (0.41 to 1.08); n=2 | 0.64 (0.43 to 0.95); n=10 | 2.73 (1.59 to 4.68); n=10 | |||||
| Intention to treat analysis:
|
|
|
|
|
|
|
|
|
|
|
| Yes
|
0.77 (0.61 to 0.97); n=4
|
0.26 | 0.80 (0.44 to 1.44); n=3
|
0.08 | 0.64 (0.40 to 1.03); n=3
|
Not estimable | 0.83 (0.67 to 1.04); n=4
|
0.001 | 2.26 (1.21 to 4.22); n=4
|
<0.001 |
| No | 1.57 (0.27 to 9.07); n=4 | 0.28 (0.11 to 0.72); n=3 | Not estimable | 0.36 (0.21 to 0.62); n=10 | 6.91 (2.89 to 16.48); n=9 | |||||
| Lost to follow up (%):
|
|
|
|
|
|
|
|
|
|
|
| 0
|
5.0 (0.55 to 45.39; n=1
|
0.56† | 0.44 (0.13 to 1.52); n=2
|
0.98† | Not estimable
|
0.37† | 0.56 (0.28 to 1.13); n=5
|
0.05† | 3.50 (2.06 to 5.95); n=7
|
0.20† |
| 1-10
|
0.79 (0.62 to 1.01); n=2
|
0.48 (0.06 to 3.82); n=2
|
0.88 (0.27 to 2.88); n=1
|
0.43 (0.18 to 1.03); n=5
|
1.72 (0.88 to 3.35); n=3
|
|||||
| 11-20
|
3.13 (0.13 to 75.49); n=1
|
Not estimable
|
Not estimable
|
0.30 (0.13 to 0.66); n=2
|
13.30 (1.76 to 100.70); n=2
|
|||||
| >20 | 0.58 (0.27 to 1.23); n=4 | 0.58 (0.37 to 0.90); n=2 | 2 0.60 (0.36 to 1.01); n=2 | 0.28 (0.06 to 1.29); n=2 | 11.79 (0.75 to 184.66); n=1 | |||||
| Duration of follow up (months):
|
|
|
|
|
|
|
|
|
|
|
| 6-23
|
2.53 (0.11 to 57.83); n=1
|
0.95† | 0.52 (0.10 to 2.69); n=1
|
0.83† | Not estimable
|
0.63† | 0.56 (0.21 to 1.48); n=3
|
0.17† | 8.63 (1.76 to 42.42); n=3
|
0.001† |
| 24-47
|
0.92 (0.22 to 3.81); n=4
|
0.55 (0.36 to 0.86); n=2
|
0.63 (0.37 to 1.07); n=1
|
0.54 (0.29 to 1.01); n=6
|
3.36 (2.04 to 5.53); n=7
|
|||||
| ≥48 | 0.79 (0.62 to 1.01); n=3 | 0.58 (0.16 to 2.14); n=3 | 0.63 (0.16 to 2.44); n=2 | 0.31 (0.12 to 0.79); n=5 | 4.12 (0.56 to 30.28); n=3 | |||||
Some data are not estimable either because no trial with this variable reported outcome or because trials in this group reported 0 events in both treatment and control arms. P values calculated through random effects metaregression analysis.
*
Calculated by analysing each category compared to first category.
†
Calculated with random effects metaregression for differences in risk across all trials considering variable on continuous scale, but relative risks and 95% confidence intervals provided for major categories.