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. 2020 Nov 3;2020(11):CD003229. doi: 10.1002/14651858.CD003229.pub4

Comparison 2. Sensitivity analysis excluding studies that allowed the use of elastic stockings.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
2.1 Oedema in the lower legs (dichotomous variable) 12 1131 Risk Ratio (M‐H, Fixed, 95% CI) 0.68 [0.60, 0.76]
2.1.1 Aminaftone 1 82 Risk Ratio (M‐H, Fixed, 95% CI) 0.53 [0.28, 0.99]
2.1.2 Calcium dobesilate 2 290 Risk Ratio (M‐H, Fixed, 95% CI) 0.72 [0.48, 1.07]
2.1.3 Diosmine, Hidrosmine 2 144 Risk Ratio (M‐H, Fixed, 95% CI) 0.63 [0.46, 0.86]
2.1.4 Grape seed extract 1 75 Risk Ratio (M‐H, Fixed, 95% CI) 0.79 [0.58, 1.06]
2.1.5 Rutosides 6 540 Risk Ratio (M‐H, Fixed, 95% CI) 0.68 [0.58, 0.78]
2.2 Ankle perimeter circumference (mm) 10 1212 Mean Difference (IV, Fixed, 95% CI) ‐4.59 [‐6.02, ‐3.16]
2.2.1 Calcium dobesilate 3 502 Mean Difference (IV, Fixed, 95% CI) ‐0.80 [‐4.95, 3.34]
2.2.2 Diosmine, Hidrosmine 2 246 Mean Difference (IV, Fixed, 95% CI) ‐5.90 [‐7.72, ‐4.07]
2.2.3 Rutosides 5 464 Mean Difference (IV, Fixed, 95% CI) ‐3.28 [‐6.06, ‐0.50]
2.3 Volume of the leg (mL) 9 1153 Std. Mean Difference (IV, Fixed, 95% CI) ‐0.30 [‐0.42, ‐0.19]
2.3.1 Aminaftone 1 79 Std. Mean Difference (IV, Fixed, 95% CI) ‐0.17 [‐0.61, 0.28]
2.3.2 Calcium dobesilate 3 587 Std. Mean Difference (IV, Fixed, 95% CI) ‐0.33 [‐0.49, ‐0.17]
2.3.3 Rutosides 5 487 Std. Mean Difference (IV, Fixed, 95% CI) ‐0.29 [‐0.47, ‐0.11]
2.4 Quality of life 3 1022 Std. Mean Difference (IV, Random, 95% CI) ‐0.13 [‐0.41, 0.15]
2.4.1 Aminaftone 1 79 Std. Mean Difference (IV, Random, 95% CI) ‐0.64 [‐1.10, ‐0.19]
2.4.2 Calcium dobesilate 1 351 Std. Mean Difference (IV, Random, 95% CI) ‐0.03 [‐0.23, 0.18]
2.4.3 Diosmine, Hidrosmine 1 592 Std. Mean Difference (IV, Random, 95% CI) 0.04 [‐0.12, 0.20]
2.5 Ulcer healing 2 128 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.27, 3.10]
2.5.1 Aminaftone 1 100 Risk Ratio (M‐H, Random, 95% CI) 0.75 [0.18, 3.18]
2.5.2 Diosmine, Hidrosmine 1 28 Risk Ratio (M‐H, Random, 95% CI) 1.50 [0.15, 14.68]
2.6 Trophic disorders (dichotomous variable) 5 601 Risk Ratio (M‐H, Fixed, 95% CI) 0.86 [0.79, 0.94]
2.6.1 Aminaftone 1 97 Risk Ratio (M‐H, Fixed, 95% CI) 0.77 [0.41, 1.44]
2.6.2 Diosmine, Hidrosmine 4 504 Risk Ratio (M‐H, Fixed, 95% CI) 0.87 [0.81, 0.94]
2.7 Pain in the lower legs (dichotomous variable) 18 1818 Risk Ratio (M‐H, Random, 95% CI) 0.70 [0.60, 0.82]
2.7.1 Aminaftone 1 97 Risk Ratio (M‐H, Random, 95% CI) 0.43 [0.23, 0.79]
2.7.2 Calcium dobesilate 5 705 Risk Ratio (M‐H, Random, 95% CI) 0.53 [0.35, 0.82]
2.7.3 Diosmine, Hidrosmine 4 271 Risk Ratio (M‐H, Random, 95% CI) 0.82 [0.63, 1.08]
2.7.4 Rutosides 8 745 Risk Ratio (M‐H, Random, 95% CI) 0.75 [0.61, 0.91]
2.8 Pain in the lower legs (continuous variable) 6   Std. Mean Difference (IV, Random, 95% CI) Subtotals only
2.8.1 Calcium dobesilate 1 351 Std. Mean Difference (IV, Random, 95% CI) ‐0.21 [‐0.42, 0.00]
2.8.2 Diosmine, Hidrosmine 3 846 Std. Mean Difference (IV, Random, 95% CI) ‐0.23 [‐0.41, ‐0.05]
2.8.3 Rutosides 2 164 Std. Mean Difference (IV, Random, 95% CI) ‐0.96 [‐1.33, ‐0.59]
2.9 Cramps in the lower legs (dichotomous variable) 12 1603 Risk Ratio (M‐H, Random, 95% CI) 0.72 [0.57, 0.91]
2.9.1 Aminaftone 1 97 Risk Ratio (M‐H, Random, 95% CI) 0.56 [0.31, 0.99]
2.9.2 Calcium dobesilate 2 255 Risk Ratio (M‐H, Random, 95% CI) 0.65 [0.50, 0.84]
2.9.3 Diosmine, Hidrosmine 2 104 Risk Ratio (M‐H, Random, 95% CI) 0.87 [0.69, 1.09]
2.9.4 Rutosides 7 1147 Risk Ratio (M‐H, Random, 95% CI) 0.73 [0.50, 1.06]
2.10 Cramps in the lower legs (continuous variable) 3 314 Std. Mean Difference (IV, Random, 95% CI) ‐0.70 [‐1.15, ‐0.24]
2.10.1 Diosmine, Hidrosmine 1 150 Std. Mean Difference (IV, Random, 95% CI) ‐0.46 [‐0.78, ‐0.14]
2.10.2 Rutosides 2 164 Std. Mean Difference (IV, Random, 95% CI) ‐0.83 [‐1.50, ‐0.16]
2.11 Restless legs (dichotomous variable) 6 572 Risk Ratio (M‐H, Fixed, 95% CI) 0.81 [0.72, 0.91]
2.11.1 Calcium dobesilate 2 255 Risk Ratio (M‐H, Fixed, 95% CI) 0.73 [0.59, 0.91]
2.11.2 Diosmine, Hidrosmine 1 70 Risk Ratio (M‐H, Fixed, 95% CI) 0.90 [0.70, 1.15]
2.11.3 Rutosides 3 247 Risk Ratio (M‐H, Fixed, 95% CI) 0.86 [0.73, 1.01]
2.12 Itching in the lower legs (dichotomous variable) 4   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
2.12.1 Aminaftone 1 97 Risk Ratio (M‐H, Random, 95% CI) 0.53 [0.31, 0.91]
2.12.2 Diosmine, Hidrosmine 1 34 Risk Ratio (M‐H, Random, 95% CI) 1.63 [0.51, 5.25]
2.12.3 Rutosides 2 274 Risk Ratio (M‐H, Random, 95% CI) 0.68 [0.21, 2.21]
2.13 Itching in the lower legs (continuous variable) 1   Std. Mean Difference (IV, Fixed, 95% CI) Totals not selected
2.13.1 Rutosides 1   Std. Mean Difference (IV, Fixed, 95% CI) Totals not selected
2.14 Heaviness in the lower legs (dichotomous variable) 16   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
2.14.1 Aminaftone 1 97 Risk Ratio (M‐H, Random, 95% CI) 0.32 [0.17, 0.60]
2.14.2 Calcium dobesilate 3 305 Risk Ratio (M‐H, Random, 95% CI) 0.33 [0.08, 1.42]
2.14.3 Centella asiatica 1 63 Risk Ratio (M‐H, Random, 95% CI) 0.62 [0.32, 1.19]
2.14.4 Diosmine, Hidrosmine 3 201 Risk Ratio (M‐H, Random, 95% CI) 0.60 [0.29, 1.22]
2.14.5 Rutosides 8 531 Risk Ratio (M‐H, Random, 95% CI) 0.55 [0.38, 0.80]
2.15 Heaviness in the lower legs (continuous variable) 6   Std. Mean Difference (IV, Random, 95% CI) Subtotals only
2.15.1 Diosmine, Hidrosmine 1 150 Std. Mean Difference (IV, Random, 95% CI) ‐0.69 [‐1.02, ‐0.36]
2.15.2 Rutosides 5 360 Std. Mean Difference (IV, Random, 95% CI) ‐1.27 [‐2.22, ‐0.32]
2.16 Swelling in the lower legs (dichotomous variable) 12 952 Risk Ratio (M‐H, Random, 95% CI) 0.66 [0.53, 0.82]
2.16.1 Calcium dobesilate 2 80 Risk Ratio (M‐H, Random, 95% CI) 0.19 [0.08, 0.41]
2.16.2 Diosmine, Hidrosmine 2 104 Risk Ratio (M‐H, Random, 95% CI) 0.70 [0.52, 0.94]
2.16.3 Rutosides 8 768 Risk Ratio (M‐H, Random, 95% CI) 0.72 [0.58, 0.89]
2.17 Swelling in the lower legs (continuous variable) 4   Std. Mean Difference (IV, Random, 95% CI) Subtotals only
2.17.1 Diosmine, Hidrosmine 1 150 Std. Mean Difference (IV, Random, 95% CI) ‐0.92 [‐1.26, ‐0.58]
2.17.2 Rutosides 3 264 Std. Mean Difference (IV, Random, 95% CI) ‐1.73 [‐3.50, 0.04]
2.18 Paraesthesias in the lower legs (dichotomous variable) 7 716 Risk Ratio (M‐H, Fixed, 95% CI) 0.75 [0.64, 0.88]
2.18.1 Calcium dobesilate 3 305 Risk Ratio (M‐H, Fixed, 95% CI) 0.77 [0.58, 1.01]
2.18.2 Diosmine, Hidrosmine 2 144 Risk Ratio (M‐H, Fixed, 95% CI) 0.81 [0.61, 1.06]
2.18.3 Rutosides 2 267 Risk Ratio (M‐H, Fixed, 95% CI) 0.68 [0.51, 0.91]
2.19 Paraesthesias in the lower legs (continuous variable) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
2.19.1 Diosmine, Hidrosmine 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
2.20 Participant satisfaction (dichotomous variable) 12 1193 Risk Ratio (M‐H, Random, 95% CI) 0.69 [0.53, 0.90]
2.20.1 Calcium dobesilate 3 515 Risk Ratio (M‐H, Random, 95% CI) 0.71 [0.43, 1.17]
2.20.2 Diosmine, Hidrosmine 2 171 Risk Ratio (M‐H, Random, 95% CI) 0.84 [0.68, 1.04]
2.20.3 Rutosides 7 507 Risk Ratio (M‐H, Random, 95% CI) 0.52 [0.28, 0.98]
2.21 Participant satisfaction (continuous variable) 4   Std. Mean Difference (IV, Random, 95% CI) Totals not selected
2.21.1 Diosmine, Hidrosmine 1   Std. Mean Difference (IV, Random, 95% CI) Totals not selected
2.21.2 Rutosides 3   Std. Mean Difference (IV, Random, 95% CI) Totals not selected
2.22 Adverse events 27 3433 Risk Ratio (M‐H, Fixed, 95% CI) 1.12 [0.95, 1.33]
2.22.1 Aminaftone 1 79 Risk Ratio (M‐H, Fixed, 95% CI) 0.60 [0.06, 6.32]
2.22.2 Calcium dobesilate 5 935 Risk Ratio (M‐H, Fixed, 95% CI) 1.12 [0.82, 1.53]
2.22.3 Centella asiatica 1 94 Risk Ratio (M‐H, Fixed, 95% CI) 1.14 [0.58, 2.23]
2.22.4 Diosmine, Hidrosmine 7 1124 Risk Ratio (M‐H, Fixed, 95% CI) 0.97 [0.74, 1.27]
2.22.5 Grape seed extract 1 75 Risk Ratio (M‐H, Fixed, 95% CI) 0.57 [0.19, 1.74]
2.22.6 Rutosides 12 1126 Risk Ratio (M‐H, Fixed, 95% CI) 1.54 [1.08, 2.19]