Article Figures & Data
Figures
- Figure 1
Flow chart of the study. eGFR, estimated glomerular filtration rate; TRACE-2, tenecteplase vs alteplase in acute ischaemic cerebrovascular events.
Tables
- Table 1
Baseline characteristics of intravenous thrombolysis-treated patients according to renal function
Characteristics Tenecteplase Alteplase eGFR≥90 mL/min/1.73 m2
(n=465)eGFR 60–89 mL/min/1.73 m2
(n=195)eGFR<60 mL/min/1.73 m2
(n=45)P value eGFR≥90
mL/min/1.73 m2 (n=486)eGFR 60–89
mL/min/1.73 m2 (n=171)eGFR<60 mL/min/1.73 m2
(n=50)P value Age, years 62.36±10.54 71.12±10.37 73.82±11.80 <0.001 62.11±10.34 69.56±9.74 75.56±11.87 <0.001 Females, n (%) 130 (27.96) 64 (32.82) 22 (48.89) 0.01 144 (29.63) 64 (37.43) 20 (40.00) 0.08 Body mass index, kg/m2 23.99±3.45 23.65±3.63 22.50±3.77 0.02 24.31±3.44 23.95±3.58 23.46±3.39 0.18 National Institutes of Health Stroke Scale scale 7.0 (5.0 to 10.0) 7.0 (5.0 to 10.0) 7.0 (5.0 to 12.0) 0.76 7.0 (6.0 to 10.0) 8.0 (6.0 to 11.0) 6.0 (5.0 to 10.0) 0.12 Medical history Hypertension, n (%) 315 (67.74) 152 (77.95) 39 (86.67) 0.007 339 (69.75) 128 (74.85) 45 (90.00) 0.007 Diabetes, n (%) 110 (23.66) 47 (24.10) 13 (28.89) 0.74 137 (28.19) 55 (32.16) 15 (30.00) 0.61 Hyperlipidaemia, n (%) 90 (19.35) 34 (17.44) 5 (11.11) 0.37 114 (23.46) 35 (20.47) 11 (22.00) 0.72 Coronary heart disease, n (%) 97 (20.86) 53 (27.18) 16 (35.56) 0.03 102 (20.99) 46 (26.90) 18 (36.00) 0.03 Arrhythmia, n (%) 67 (14.41) 55 (28.21) 13 (28.89) <0.001 79 (16.26) 48 (28.07) 19 (38.00) <0.001 Current smoker, n (%) 196 (42.24) 54 (27.69) 14 (31.11) 0.004 213 (43.92) 53 (30.99) 10 (20.00) <0.001 History of medication use, n (%) Antiplatelet agents 53 (11.40) 31 (15.90) 6 (13.33) 0.28 55 (11.32) 23 (13.45) 14 (28.00) 0.004 Anticoagulant agents 1 (0.22) 4 (2.05) 0 (0.00) 0.03 3 (0.62) 4 (2.34) 0 (0.00) 0.11 Lipid-lowering drugs 32 (6.88) 28 (14.36) 7 (15.56) 0.004 34 (7.00) 17 (9.94) 9 (18.00) 0.02 Hypoglycaemic drugs 74 (15.91) 26 (13.33) 7 (15.56) 0.70 77 (15.84) 34 (19.88) 7 (14.00) 0.41 Antihypertensive drugs 181 (38.92) 94 (48.21) 19 (42.22) 0.09 203 (41.77) 84 (49.12) 31 (62.00) 0.01 Modified Rankin Scale score before stroke 0.34 0.07 0 421 (90.54) 169 (86.67) 40 (88.89) 438 (90.12) 155 (90.64) 40 (80.00) 1 44 (9.46) 26 (13.33) 5 (11.11) 48 (9.88) 16 (9.36) 10 (20.00) Onset-to-needle time, hours 179.05±55.96 176.65±55.68 163.02±45.55 0.13 182.80±56.72 171.17±56.95 181.10±58.53 0.09 Bridging thrombectomy, n% 19 (4.09) 6 (3.08) 2 (4.44) 0.81 16 (3.29) 8 (4.68) 0 (0.00) 0.27 eGFR, mL/min/1.73 m2 107.93±11.32 78.19±7.92 46.58±12.53 <0.001 107.30±10.27 76.90±9.06 46.51±10.74 <0.001 Serum creatinine, umol/L 63.12±11.21 87.17±13.57 139.91±67.71 <0.001 63.79±11.94 88.42±14.67 135.95±46.45 <0.001 Data are expressed as mean ± SD, median (IQR) or n (%).
eGFR, estimated glomerular filtration rate.
- Table 2
Efficacy outcomes according to eGFR category in patients treated with tenecteplase
eGFR (mL/min/1.73 m2) Event rate (%) Crude effect size (95% CI) P value Adjusted effect size (95% CI)* P value Primary outcome mRS score 0–1 at 90 days ≥90 302 (65.5) 1 1 60–89 114 (58.8) 0.75 (0.53 to 1.06) 0.10 0.92 (0.61 to 1.39) 0.68 ＜60 21 (46.7) 0.46 (0.25 to 0.85) 0.01 0.60 (0.30 to 1.25) 0.17 Secondary outcome mRS score 0–2 at 90 days ≥90 355 (77.0) 1 1 60–89 132 (68.0) 0.64 (0.44 to 0.92) 0.02 0.78 (0.50 to 1.23) 0.29 ＜60 26 (57.8) 0.41 (0.22 to 0.77) 0.01 0.58 (0.27 to 1.27) 0.18 European Health-Related Quality of Life at 90 days ≥90 80 (70 to 91) 1 1 60–89 80 (60 to 95) −0.61
(−4.16 to 2.93)0.73 0.74 (−2.81 to 4.30) 0.68 ＜60 80 (55 to 90) −6.33
(−13.28 to 0.62)0.07 −3.94 (−10.63 to 2.75) 0.25 Barthel index score≥95 at 90 days ≥90 325 (73.0) 1 1 60–89 114 (65.2) 0.70 (0.48 to 1.02) 0.06 1.14 (0.73 to 1.78) 0.56 ＜60 21 (60.0) 0.55 (0.27 to 1.12) 0.10 1.23 (0.53 to 2.81) 0.63 Data are expressed as n/N (%), effect size (95% CI), median (IQR) or p value.
Scores on the mRS range from 0 to 6, with 0 indicating no disability, 3 indicating moderate disability and 6 indicating death.
The association between eGFR as a categorical variable and the efficacy and safety outcome was estimated by calculating the ORs with 95% CIs using binary logistic regression models. β-coefficient with its 95% CI was calculated using general linear model for the outcome of European quality of life visual analogue scale.
*The models were adjusted for age, sex, baseline National Institutes of Health Stroke Scale, history of hypertension, history of antiplatelet and anticoagulant drug use, onset-to-needle time and bridging thrombectomy.
eGFR, estimated glomerular filtration rate; mRS, modified Rankin Scale.
- Table 3
Safety outcomes according to eGFR category in patients treated with tenecteplase
eGFR (mL/min/1.73 m2) Event rate (%) Crude OR
(95% CI)P value Adjusted OR
(5% CI)*P value Symptomatic intracranial haemorrhage within 36 hours ≥90 7 (1.5) 1 1 60–89 7 (3.6) 2.44 (0.84 to 7.04) 0.10 2.01 (0.59 to 6.85) 0.27 <60 1 (2.2) 1.49 (0.18 to 12.36) 0.71 0.92 (0.09 to 9.47) 0.95 Symptomatic intracranial haemorrhage within 90 days ≥90 8 (1.7) 1 1 60–89 7 (3.6) 2.13 (0.76 to 5.95) 0.15 1.77 (0.55 to 5.66) 0.34 <60 2 (4.4) 2.66 (0.55 to 12.91) 0.23 1.86 (0.31 to 11.16) 0.50 Parenchymal haematoma 2 intracranial haemorrhage within 90 days ≥90 6 (1.3) 1 1 60–89 2 (1.0) 0.79 (0.16 to 3.96) 0.78 0.92 (0.16 to 5.40) 0.92 <60 2 (4.4) 3.56 (0.70 to 18.17) 0.13 4.68 (0.63 to 34.88) 0.13 Any intracranial haemorrhage within 90 days ≥90 23 (4.9) 1 1 60–89 15 (7.7) 1.6 (0.82,3 to 14) 0.17 1.40 (0.65 to 3.01) 0.39 <60 6 (13.3) 2.96 (1.14 to 7.69) 0.03 2.13 (0.7 to 6.50) 0.18 Death within 90 days ≥90 16 (3.4) 1 1 60–89 19 (9.8) 3.21 (1.62 to 6.33) 0.008 3.39 (1.53 to 7.53) 0.003 <60 10 (22.2) 8.02 (3.39 to 18.98) <0.001 8.95 (3.07 to 26.13) <0.001 Adverse events within 90 days ≥90 384 (82.2) 1 1 60–89 177 (91.2) 2.28 (1.31 to 3.95) 0.004 2.00 (1.11 to 3.59) 0.02 <60 44 (97.8) 9.55 (1.30 to 70.21) 0.027 7.73 (1.03 to 58.21) 0.047 Serious adverse events within 90 days ≥90 62 (13.3) 1 1 60–89 36 (18.6) 1.52 (0.97 to 2.38) 0.07 1.36 (0.82 to 2.23) 0.23 <60 17 (37.8) 3.95 (2.04 to 7.63) <0.001 3.35 (1.62 to 6.95) 0.001 Data are expressed as n/N (%), effect size (95% CI) or p value.
ORs of the safety outcomes were calculated with their 95% CIs using binary logistic regression.
*The models were adjusted for age, sex, baseline National Institutes of Health Stroke Scale, history of hypertension, history of antiplatelet and anticoagulant drug use, onset-to-needle time and bridging thrombectomy.
eGFR, estimated glomerular filtration rate.
- Table 4
Efficacy outcomes according to eGFR category in patients treated with alteplase
eGFR (mL/min/1.73 m2) Event rate (%) Crude effect size (95% CI) P value Adjusted effect size
(95% CI)*P value Primary outcome mRS score 0–1 at 90 days ≥90 293 (61.2) 1 1 60–89 86 (51.5) 0.67 (0.47 to 0.96) 0.03 0.98 (0.65 to 1.46) 0.90 <60 26 (52.0) 0.69 (0.38 to 1.23) 0.21 1.13 (0.57 to 2.24) 0.72 Secondary outcome mRS score 0–2 at 90 days ≥90 363 (75.8) 1 1 60–89 108 (64.7) 0.59 (0.40 to 0.86) 0.006 0.87 (0.56 to 1.36) 0.55 <60 31 (62.0) 0.52 (0.28 to 0.96) 0.036 0.82 (0.40 to 1.72) 0.60 European Health-Related Quality of Life at 90 days ≥90 80 (70 to 90) 1 1 60–89 80 (60 to 90) −5.84 (−9.71 to −1.97) 0.003 −3.50 (−7.45 to 0.45) 0.08 <60 80 (70 to 90) 0.72 (−6.24 to 7.67) 0.84 2.87 (−4.22 to 9.96) 0.43 Barthel index score≥95 at 90 days ≥90 331 (71.2) 1 1 60–89 95 (60.1) 1.00 (0.64 to 1.53) 0.94 1.01 (0.65 to 1.56) 0.96 <60 28 (71.8) 2.23 (0.94 to 5.28) 0.94 0.45 (0.19 to 1.07) 0.07 Data are expressed as n/N (%), effect size (95% CI), median (IQR) or p value. Scores on the mRS range from 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death.
The association between eGFR as a categorical variable and the efficacy and safety outcome was estimated by calculating the ORs with 95% CIs using binary logistic regression models. β-coefficient with its 95% CI was calculated using general linear model for the outcome of European quality of life visual analogue scale.
*The models were adjusted for age, sex, baseline National Institutes of Health Stroke Scale, history of hypertension, history of antiplatelet and anticoagulant drug use, onset-to-needle time and bridging thrombectomy.
eGFR, estimated glomerular filtration rate; mRS, modified Rankin Scale.
- Table 5
Safety outcomes according to eGFR category in patients treated with alteplase
eGFR (mL/min/1.73 m2) Event rate (%) Crude OR
(95% CI)P value Adjusted OR
(95% CI)*P value Symptomatic intracranial haemorrhage within 36 hours ≥90 5 (1.0) 1 1 60–89 5 (2.9) 2.9 (0.83 to 10.14) 0.10 3.38 (0.87 to 13.17) 0.08 <60 3 (6.0) 6.14 (1.42 to 26.5) 0.02 10.01 (1.61 to 62.15) 0.01 Symptomatic intracranial haemorrhage within 90 days ≥90 6 (1.2) 1 1 60–89 6 (3.5) 2.91 (0.93 to 9.15) 0.06 3.2 (0.92 to 11.11) 0.07 <60 3 (6.0) 5.11 (1.24 to 21.08) 0.02 7.84 (1.4 to 43.77) 0.02 Parenchymal haematoma 2 intracranial haemorrhage within 90 days ≥90 3 (0.6) 1 1 60–89 0 (0.0) NA 0.95 NA 0.94 <60 0 (0.0) NA 0.97 NA 0.96 Any intracranial haemorrhage within 90 days ≥90 26 (5.4) 1 1 60–89 17 (9.9) 1.95 (1.03 to 3.7) 0.04 1.5 (0.74 to 3.04) 0.26 <60 7 (14.0) 2.88 (1.18 to 7.02) 0.02 2.08 (0.72 to 6.01) 0.18 Other significant haemorrhage events within 90 days ≥90 3 (0.6) 1 1 60–89 0 (0.0) NA 0.97 NA 0.95 <60 2 (4.0) 6.71 (1.09 to 41.14) 0.04 10.96 (0.8 to 149.76) 0.07 Death within 90 days ≥90 14 (2.9) 1 1 60–89 10 (5.8) 1.87 (0. to 4.41) 0.15 0.93 (0.35 to 2.45) 0.88 <60 11 (22.0) 9.51 (4.05 to 22.35) <0.001 4.54 (1.48 to 13.91) 0.008 Adverse events within 90 days ≥90 408 (84.3) 1 1 60–89 157 (91.3) 1.93 (1.08 to 3.46) 0.02 1.71 (0.93 to 3.15) 0.08 <60 48 (96.0) 4.45 (1.06 to 18.69) 0.04 4.07 (0.93 to 17.73) 0.06 SeriousAdverse events within 90 days ≥90 55 (11.4) 1 1 60–89 38 (22.1) 2.16 (1.37 to 3.43) 0.001 1.81 (1.1 to 2.98) 0.02 <60 14 (28.0) 3.05 (1.55 to 6.00) 0.001 2.36 (1.09 to 5.10) 0.03 Data are expressed as n/N (%), effect size (95% CI) or p value. Risk ratios of the safety outcomes were calculated with their 95% CIs using binary logistic regression.
*The models were adjusted for age, sex, baseline National Institutes of Health Stroke Scale, history of hypertension, history of antiplatelet and anticoagulant drug use, onset-to-needle time and bridging thrombectomy.
eGFR, estimated glomerular filtration rate.
Supplementary data
