Summary of outcomes
Subgroup | N | Cilostazol | Control | RR (95% CI) | P value | I2 (%) | Test for subgroup differences | |
Ischaemic stroke recurrence | ||||||||
A | Overall | 18 | 217/5724 | 317/5705 | 0.69 (0.58–0.81) | <0.0001 | 0 | NA |
B | CIL SAPT vs SAPT | 7 | 131/2844 | 168/2837 | 0.78 (0.62–0.97) | 0.03 | 0 | χ3 2=7.50, p=0.06, I2=60.0% |
CIL DAPT vs SAPT | 8 | 43/1864 | 82/1853 | 0.52 (0.36–0.75) | 0.0005 | 0 | ||
CIL DAPT vs DAPT | 1 | 10/232 | 6/225 | 1.62 (0.60–4.37) | 0.34 | NA | ||
CIL vs No CIL | 2 | 33/784 | 61/790 | 0.54 (0.36–0.82) | 0.003 | 0 | ||
C | Stroke onset <3 days | 4 | 16/1120 | 24/1122 | 0.67 (0.36–1.25) | 0.20 | 0 | χ1 2=0.01, p=0.93, I2=0% |
Stroke onset >3 days | 14 | 201/4604 | 293/4583 | 0.69 (0.56–0.84) | 0.0002 | 8 | ||
D | Short term (<3 months) | 3 | 7/655 | 8/627 | 0.78 (0.29–2.12) | 0.63 | 0 | χ1 2=0.07, p=0.80, I2=0% |
Long term (≥3 months) | 15 | 210/5069 | 309/5078 | 0.68 (0.58–0.81) | <0.0001 | 0 | ||
E | Symptomatic ICAS | 3 | 14/382 | 12/373 | 1.10 (0.45–2.68) | 0.84 | 24 | χ2 2=1.33, p=0.52, I2=0% |
LACI | 2 | 2/131 | 1/108 | 1.08 (0.14–8.56) | 0.95 | 0 | ||
Others/mixed/unknown | 13 | 201/5211 | 304/5224 | 0.67 (0.56–0.79) | <0.00001 | 0 | ||
Any stroke recurrence | ||||||||
A | Overall | 18 | 250/5724 | 394/5705 | 0.64 (0.54–0.74) | <0.00001 | 0 | NA |
B | Stroke onset <3 days | 4 | 20/1120 | 29/1122 | 0.70 (0.39–1.23) | 0.21 | 0 | χ1 2=0.11, p=0.75, I2=0% |
Stroke onset >3 days | 14 | 230/4604 | 365/4583 | 0.63 (0.54–0.74) | <0.00001 | 0 | ||
C | Short term (<3 months) | 3 | 9/655 | 9/627 | 0.91 (0.37–2.24) | 0.83 | 0 | χ1 2=0.61, p=0.43, I2=0% |
Long term (≥3 months) | 15 | 241/5069 | 385/5078 | 0.63 (0.54–0.74) | <0.00001 | 0 | ||
D | Symptomatic ICAS | 3 | 15/382 | 14/373 | 0.96 (0.27–3.45) | 0.95 | 65 | χ2 2=0.71, p=0.70, I2=0% |
LACI | 2 | 2/131 | 1/108 | 1.08 (0.14–8.56) | 0.95 | 0 | ||
Others/mixed/unknown | 13 | 233/5211 | 379/5224 | 0.62 (0.53–0.73) | <0.00001 | 0 | ||
Intracranial haemorrhage | ||||||||
A | Overall | 18 | 37/5724 | 86/5705 | 0.46 (0.31–0.68) | <0.0001 | 0 | NA |
B | Stroke onset <3 days | 4 | 4/1120 | 5/1122 | 0.91 (0.24–3.53) | 0.89 | 0 | χ1 2=1.05, p=0.31, I2=4.8% |
Stroke onset >3 days | 14 | 33/4604 | 81/4583 | 0.43 (0.29–0.65) | <0.0001 | 0 | ||
C | Short term (<3 months) | 3 | 2/655 | 1/627 | 2.00 (0.18–22.03) | 0.57 | NA | χ1 2=1.48, p=0.22, I2=32.3% |
Long term (≥3 months) | 15 | 35/5069 | 85/5078 | 0.44 (0.30–0.66) | <0.0001 | 0 | ||
D | Symptomatic ICAS | 3 | 1/382 | 3/373 | 0.46 (0.06–3.57) | 0.46 | 0 | χ1 2=0.00, p=1.00, I2=0% |
LACI | 2 | 0/131 | 0/108 | NA | NA | NA | ||
Others/mixed/unknown | 13 | 36/5211 | 83/5224 | 0.46 (0.31–0.68) | 0.0001 | 0 | ||
Major haemorrhagic events | ||||||||
A | Overall | 14 | 44/4031 | 93/4010 | 0.49 (0.34–0.70) | <0.0001 | 0 | NA |
B | Stroke onset <3 days | 4 | 7/1120 | 13/1122 | 0.60 (0.24–1.52) | 0.28 | 0 | χ1 2=0.23, p=0.63, I2=0% |
Stroke onset >3 days | 10 | 37/2911 | 80/2888 | 0.47 (0.32–0.69) | 0.0001 | 0 | ||
C | Short term (<3 months) | 3 | 4/655 | 5/627 | 0.80 (0.22–2.97) | 0.74 | NA | χ1 2=0.59, p=0.44, I2=0% |
Long term (≥3 months) | 11 | 40/3376 | 88/3383 | 0.47 (0.32–0.68) | <0.0001 | 0 | ||
D | Symptomatic ICAS | 3 | 6/382 | 9/373 | 0.67 (0.17–2.59) | 0.56 | 37 | χ1 2=0.24, p=0.62, I2=0% |
LACI | 2 | 0/131 | 0/108 | NA | NA | NA | ||
Others/mixed/unknown | 9 | 38/3518 | 84/3529 | 0.47 (0.32–0.68) | <0.0001 | 0 | ||
Mortality | ||||||||
A | Overall | 15 | 64/5029 | 72/5017 | 0.90 (0.64–1.25) | 0.53 | 0 | NA |
B | Stroke onset <3 days | 2 | 3/482 | 1/483 | 2.33 (0.34–15.82) | 0.39 | 0 | χ1 2=0.98, p=0.32, I2=0% |
Stroke onset >3 days | 13 | 61/4547 | 71/4534 | 0.87 (0.62–1.22) | 0.43 | 0 | ||
C | Short term (<3 months) | 2 | 0/55 | 0/26 | NA | NA | NA | NA |
Long term (≥3 months) | 13 | 64/4974 | 72/4991 | 0.90 (0.64–1.25) | 0.53 | 0 | ||
D | Symptomatic ICAS | 3 | 2/382 | 3/373 | 0.67 (0.11–4.06) | 0.66 | 0 | χ1 2=0.11, p=0.74, I2=0% |
LACI | 2 | 0/131 | 0/108 | NA | NA | NA | ||
Others/mixed/unknown | 10 | 62/4516 | 69/4536 | 0.91 (0.65–1.27) | 0.58 | 0 | ||
MACE | ||||||||
A | Overall | 13 | 184/3826 | 276/3842 | 0.67 (0.56–0.81) | <0.0001 | 0 | NA |
B | Stroke onset <3 days | 4 | 25/1120 | 33/1122 | 0.76 (0.45–1.27) | 0.30 | 0 | χ1 2=0.18, p=0.67, I2=0% |
Stroke onset >3 days | 9 | 159/2706 | 243/2720 | 0.67 (0.52–0.86) | 0.002 | 20 | ||
C | Short term (<3 months) | 2 | 12/613 | 12/612 | 1.00 (0.45–2.21) | 1.00 | NA | χ1 2=1.03, p=0.31, I2=3.0% |
Long term (≥3 months) | 11 | 172/3213 | 264/3230 | 0.66 (0.55–0.79) | <0.0001 | 0 | ||
D | Symptomatic ICAS | 2 | 17/299 | 12/293 | 1.38 (0.67–2.85) | 0.38 | 0 | χ2 2=4.22, p=0.12, I2=52.6% |
LACI | 1 | 1/89 | 1/93 | 1.04 (0.07–16.45) | 0.98 | NA | ||
Others/mixed/unknown | 10 | 166/3438 | 263/3456 | 0.64 (0.53–0.77) | <0.00001 | 0 |
CIL, cilostazol; DAPT, dual antiplatelet therapy; ICAS, intracranial arterial stenosis; LACI, lacunar infarction; No CIL, placebo or best medical therapy; RR, risk ratio; SAPT, single antiplatelet therapy.