Patients
The study included 222 patients (120 in the low-dose statin group, 66 in the medium-dose statin group and 36 in the control group) whose baseline data were analysed. We lost 17 patients’ data to follow-up, and the partial outcome data of 205 patients were acquired.
Among the 222 patients (mean age: 70.77 ± 12.475 years), 109 (49.1%) were male. The median and interquartile ranges of the NIHSS at admission were 8 (5–14). Comparing the baseline data of the different groups, the low- and medium-dose statin groups had a higher percentage of antiplatelet drug use in the hospital, a lower percentage of cardioembolic and anticoagulation drug use in the hospital, and lower NIHSS scores at admission than the control group. No significant difference in other baseline data was found between the two groups (Table 01).
Table 01
variables
|
Low dose group(n = 120)
|
Medium dose group(n = 66)
|
Control group
(n = 36)
|
P*
|
Age, years, mean(SD)
|
70.93(13.007)
|
69.86(10.318)
|
71.92(14.377)
|
0.225
|
Male,%
|
58(48.3)
|
33(50)
|
18(50)
|
0.981
|
Admission NIHSS score, Med(IQR)
|
8(5–15)
|
8(4–13)
|
15(8–18)
|
0.005
|
antiplatelet drug in hospital,%
|
105(87.5)
|
61(92.4)
|
8(22.2)
|
< 0.001
|
cardioembolic,%
|
50(41.7)
|
13(19.7)
|
21(58.3)
|
< 0.001
|
Anticoagulation in hospital,%
|
38(31.7)
|
8(12.1)
|
18(50)
|
< 0.001
|
systolic blood pressure
mmHg, mean(SD)
|
147.95(25.045)
|
149.42(23.813)
|
153.81(31.962)
|
0.494
|
diastolic blood pressure
mmHg, mean(SD)
|
83.46(16.357)
|
86.14(15.685)
|
85.19(17.214)
|
0.544
|
smoking,%
|
37(30.8)
|
27(40.9)
|
10(27.8)
|
0.291
|
hypertension,%
|
54(45)
|
32(48.5)
|
18(50)
|
0.827
|
diabetes mellitus,%
|
24(20)
|
10(15.2)
|
8(22.2)
|
0.958
|
coronary heart disease,%
|
17(14.2)
|
5(7.6)
|
4(11.1)
|
0.406
|
atrial fibrillation,%
|
38(31.7)
|
23(34.8)
|
18(50)
|
0.132
|
antiplatelet drug,%
|
10(8.3)
|
4(6.1)
|
2(5.6)
|
0.411
|
antihypertensive,%
|
33(27.5)
|
13(19.7)
|
12(33.3)
|
0.425
|
hypoglycaemic,%
|
18(15)
|
6(9)
|
6(16.7)
|
0.574
|
anticoagulation,%
|
8(6.7)
|
2(3)
|
3(8.3)
|
0.757
|
Platelet, mmol/l, mean(SD)
|
177.34(52.902)
|
184.91(52.469)
|
173.97(57.457)
|
0.385
|
INR, mean(SD)
|
0.98(0.090)
|
0.97(0.127)
|
0.99(0.111)
|
0.411
|
ALT, mmol/l, mean(SD)
|
21.66(13.933)
|
22.41(9.387)
|
21.86(12.836)
|
0.203
|
Creatinine, mmol/l, mean(SD)
|
78.43(28.726)
|
77.62(25.155)
|
82.22(28.129)
|
0.508
|
Glucose, mmol/l, mean(SD)
|
7.83(2.511)
|
7.74(2.732)
|
7.99(3.397)
|
0.791
|
Triglyceride, mmol/l, mean(SD)
|
1.80(1.491)
|
1.65(1.336)
|
1.55(0.987)
|
0.874
|
Total cholesterol, mmol/l, mean(SD)
|
4.57(1.089)
|
4.45(0.960)
|
4.19(0.908)
|
0.158
|
HDL-C, mmol/l, mean(SD)
|
1.27(0.385)
|
1.33(0.405)
|
1.31(0.446)
|
0.673
|
LDL-C, mmol/l, mean(SD)
|
2.67(0.962)
|
2.70(0.771)
|
2.41(0.694)
|
0.238
|
P* was calculated by ANOVA, Chi-square test, or Mann-Whitney U test as appropriate. Mean value, SD standard distance, Med median value, IQR interquartile range, INR international normalized ratio, ALT glutamic-pyruvic transaminase, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein
|
The types of statins included simvastatin (n = 2), atorvastatin (n = 141), and rosuvastatin (n = 43), and the type of statins in the different dose statin groups was not significantly different (Table 02).
Table 02
Difference type of statins
Type of statins
|
Low dose group(n = 120)
|
Medium dose group(n = 66)
|
P*
|
atorvastatin,%
|
95(79.2)
|
48(72.7)
|
0.141
|
rosuvastatin,%
|
25(20.8)
|
16(24.2)
|
0.141
|
simvastatin,%
|
0(0)
|
2(3.1)
|
0.141
|
P* was calculated by Chi-square test.
|
Efficacy outcome
We found that the low- (p < 0.001) and medium-dose (p < 0.001) statin groups had a higher percentage of improvement at 7 days than the control group, and the low- and medium-dose statin groups did not show a significant difference (p = 0.05). The low- (p = 0.027) and medium-dose (p = 0.003) statin groups had a higher percentage of FFOs at 90 days (p = 0.027) than the control group, and the low- and medium-dose statin groups did not show a significant difference (p = 0.246). (Table 03).
Table 03
outcome
|
Control
|
Low dose
|
Medium dose
|
P1
|
P2
|
P3
|
P4
|
NIHSS improvement,%
|
41.7%
|
83.3%
|
75.8%
|
0.000
|
0.000
|
0.000
|
0.050
|
FFO,%
|
42.9%
|
63.8%
|
73.4%
|
0.000
|
0.027
|
0.003
|
0.246
|
ICH,%
|
44.4%
|
13.3%
|
4.5%
|
0.000
|
0.000
|
0.000
|
0.058
|
gastrointestinal haemorrhage,%
|
11.1%
|
0.8%
|
0%
|
0.004
|
0.010
|
0.014
|
1.000
|
Death within 2 years,%
|
33.3%
|
9.2%
|
6.1%
|
0.000
|
0.002
|
0.001
|
0.348
|
P* was calculated by Chi-square test, P1:P between three group, P2: P between control group and low dose statins group; P3:P between control group and medium dose statins group; P4:P between low dose statins group and low dose statins group.
|
In the univariate logistic regression analysis, we found that the use of statins (OR = 3.640, P < 0.001) and the use of antiplatelet drugs in the hospital (OR = 2.892, P < 0.001) were related to a higher percentage of NIHSS score improvement at 7 days after admission (Fig. 01). Using statins (OR = 1.882, P = 0.004) and the use of antiplatelet drugs in hospitals (OR = 1.512, P = 0.008) were associated with FFO at 90 days. Higher NIHSS at admission (OR = 0.956, P = 0.037), higher NIHSS at 7 days after admission (OR = 0.938, P < 0.001), older age (OR = 0.975, P = 0.039), higher systolic pressure (OR = 0.985, P = 0.007) and ICH in the hospital (OR = 0.452, P = 0.036) were inversely related to FFO at 90 days (Fig. 01).
In the multivariable logistic regression analysis, after adjusting for risk factors, we found that the use of statins (OR = 2.291, P = 0.014) and the use of antiplatelet drugs in the hospital (OR = 2.039, P = 0.012) were still related to a higher percentage of NIHSS score improvement at 7 days after admission (Fig. 02). Higher NIHSS at 7 days after admission (OR = 0.952, P = 0.009) and higher systolic pressure (OR = 0.986, P = 0.025) were still significantly inversely related to FFO at 90 days (Fig. 02).
Safety outcome
When we evaluated ICH and gastrointestinal haemorrhage events in the hospital, we found that the low- (p < 0.001) and medium-dose (p < 0.001) statin groups had a lower percentage of events than the control group, and the low- and medium-dose statin groups had no significant difference (p = 0.058). Regarding death events at the 2-year follow-up, we found that the low- (p = 0.002) and medium-dose (p = 0.001) statin groups had a lower percentage than the control group, and the low- and medium-dose statin groups had no significant difference (p = 0.348). (Table 03).
In the univariate logistic regression analysis, we found that the use of statins (OR = 0.224, P < 0.001), use of antiplatelet drugs in the hospital (OR = 0.270, P < 0.001) and higher value of platelets (OR = 0.989, P = 0.010) were inversely related to a higher percentage of ICH in the hospital (Fig. 03). Cardioembolic stroke (OR = 2.096, P = 0.049) and a higher value of LDL-C (OR = 2.791, P = 0.020) were related to a higher percentage of ICH in the hospital (Fig. 03). Using statins (OR = 0.062, P = 0.011) was inversely related to a higher percentage of gastrointestinal haemorrhage in the hospital (Fig. 3). Older age (OR = 1.193, P = 0.019) and a higher value of blood glucose (OR = 1.220, P = 0.019) were related to a higher percentage of gastrointestinal haemorrhage in the hospital (Fig. 03). We also found that the use of statins (OR = 0.110, P < 0.001) and the use of antiplatelet drugs in hospitals (OR = 0.302, P < 0.001) were inversely related to a higher percentage of death events within 2 years. Older age (OR = 1.061, P = 0.002), higher NIHSS at admission (OR = 1.073, P = 0.005) and higher NIHSS at 7 days after admission (OR = 1.130, P < 0.001) were related to a higher percentage of death events within 2 years (Fig. 03).
In the multivariable logistic regression analysis, after adjusting for risk factors, we found that the use of statins (OR = 0.379, P = 0.008), use of antiplatelet drugs in the hospital (OR = 0.395, P = 0.003) and higher value of platelets (OR = 0.990, P = 0.028) were still inversely related to a higher percentage of intracerebral haemorrhage in the hospital (Fig. 04). A higher value of LDL-C (OR = 3.133, P = 0.033) was still related to a higher percentage of ICH in the hospital. Using statins (OR = 0.027, P = 0.023) was still inversely related to a higher percentage of gastrointestinal haemorrhage in the hospital. Older age (OR = 1.413, P = 0.027) and a higher value of blood glucose (OR = 1.399, P = 0.029) were related to a higher percentage of gastrointestinal haemorrhage in the hospital (Fig. 04). Using statins (OR = 0.196, P < 0.001) was still inversely associated with a higher percentage of death events within 2 years. Older age (OR = 1.054, P = 0.015) and higher NIHSS at 7 days after admission (OR = 1.093, P < 0.001) were still related to a higher percentage of death events at 2 years (Fig. 04).
When we analysed death events in the different groups at different times with Kaplan-Meier curves, we found that the low- and medium-dose statin groups had a significantly higher survival rate than the control group at different times. The low-dose and medium-dose groups had similar survival rates within 20 months. After 20 months, the medium-dose group had a higher survival rate than the low-dose group (Fig. 05).
In the subgroup analysis, in mild stroke patients, statin use was only significantly inversely related to ICH (OR = 0.018) in the hospital. Using statins were not related to other outcomes. In moderate stroke patients, using statins was significantly related to NIHSS improvement (OR = 2.886) and was significantly inversely related to ICH (OR = 0.306) in the hospital and death event rates (OR = 0.091) at 2 years. Using statins was not related to gastrointestinal haemorrhage in the hospital or FFO at 90 days. In severe stroke patients, statin use was significantly inversely related to ICH (OR = 0.278) in the hospital and death event rates (OR = 0.204) at 2 years. Using statins was not related to NIHSS improvement or gastrointestinal haemorrhage in the hospital or FFO at 90 days (Fig. 06). In the cardioembolic stroke subgroup, statin use was significantly inversely related to death event rates (OR = 0.245) at 2 years. Using statins was not related to NIHSS improvement or ICH in the hospital or FFO at 90 days. In the noncardioembolic stroke subgroup, statin using was not related to NIHSS improvement (OR = 1.938) or FFO at 90 days (OR = 2.08) or gastrointestinal haemorrhage in the hospital. Statin using was significantly inversely related to ICH (OR = 0.129) in the hospital and death event rates (OR = 0.043) at 2 years (Fig. 07).