Low-dose versus standard-dose recombinant tissue plasminogen activator in the very elderly patients with acute ischaemic stroke: a single-center study in Tianjin, China

doi:10.21203/rs.3.rs-1999955/v1

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Low-dose versus standard-dose recombinant tissue plasminogen activator in the very elderly patients with acute ischaemic stroke: a single-center study in Tianjin, China

https://doi.org/10.21203/rs.3.rs-1999955/v1

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Objective: The optimal dose of recombinant tissue plasminogen activator for acute ischemic stroke among the very elderly patients (aged ≥80 years) in China is unclear. We aimed to assess the efficacy and safety of low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) rt-PA for varying severity and age of Chinese geriatric stroke patients.

Methods: According to dose of rt-PA, the enrolled patients were divided into two groups: rt-PA low-dose group (0.6 mg/kg) and rt-PA standard-dose group (0.9 mg/kg). The efficacy outcome was favorable functional outcome(modified Rankin Scale score of ≤2) at 90 days. The short-term safety outcomes were intracerebral hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and fatal intracerebral hemorrhage (fICH). The long-term safety outcome was death within 90 days. We assessed the efficacy and safety of low-dose vs standard-dose of rt-PA for acute ischemic stroke in Chinese very elderly patients.

Results: A total of 201 eligible patients were enrolled; among them, 93 patientswere treated with low-dose rt-PA and 108 patients received standard-dose rt-PA. The incidences of ICH, sICH and fICH in rt-PA low-dose group were lower than rt-PA standard-dose group [8.6%(8/93) vs. 19.4%(21/108), 4.3%(4/93) vs. 10.2%(11/108), 1.1%(1/93) vs. 9.3%(10/108); unadjusted and adjusted P< .05]. There were no statistically significant differences between the two groups concerning the long-term safety index and the effectiveness index. Stratification by stroke severity and age，the favorable functional outcome rate at 90 days of moderate stroke sub-group and ≥90 years old in rt-PA low-dose group were both higher than rt-PA standard-dose group [76.3%(29/38) vs. 52.6%(20/38), 56.5%(13/23) vs. 25.0%(5/20); P< .05] and without a higher risk of mortality (mRS score of 6; P> .05).

Conclusions: The efficacy and safety at 90 days of low-dose (0.6 mg/kg) rt-PA intravenous thrombolytic therapy for Chinese geriatric AIS patients was equivalent to the standard-dose (0.9 mg/kg) rt-PA but with a lower risk of ICH, sICH and fICH. For AIS patients with moderate stroke and age 90 years or older, intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended. Confirmation of the results through multicentre, prospective, randomised trial is required.

Elderly patients

Acute ischemic stroke

Intravenous

Thromblysis

Low dose

Standard dose

Recombinant tissue plasminogen activator

Intravenous thrombolysis of recombinant tissue plasminogen activator (rt-PA) is currently the only approved and recommended systemic reperfusion treatment for acute ischemic stroke (AIS) patients within 4.5 hours after symptom onset in China. As the very elderly patients (aged ≥ 80 years) were often excluded in randomised clinical trials of thrombolysis, so that available data on efficacy and safety of rt-PA in the very elderly patients are limited [1]. Although the European Stroke Organisation recommends intravenous thrombolytic therapy with rt-PA for the very elderly patients within 4.5 h after symptom onset, there is no specific dose regulation of rt-PA [2]. Subgroup secondary analysis of ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED) trial compared the effects of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous rt-PA on 90-day disability outcomes and symptomatic intracerebral haemorrhage (sICH) [3]. ENCHANTED trial’s results showed that although the sICH rates were lower with low-dose rt-PA, they could not be associated with increasing age and did not influence the differential treatment effect between the rt-PA doses on the disability outcomes [4]. Thus, ENCHANTED trial suggests that age is not a sufficient criterion to determine which dose of rt-PA to use; older patients with AIS should not be systematically denied use of standard-dose rt-PA on the assumption that it is a more hazardous treatment for very old patients than for younger patients [4]. However, Chinese participants aged ≥ 80 years were under-represented in ENCHANTED trial, accounting for only 6.8% of 1,419 Chinese patients (48%;totaling N.=3310 participants) [3]. Meanwhile, Asian had higher rates of t-PA-related intracranial hemorrhage because of the racial differences in blood coagulation-fibrinolysis factors [5]. As a consequence, it remains controversial whether ENCHANTED trial’s suggestion would directly translate into clinical practice for Asia, especially China. We report here our experience treating patients aged ≥ 80 years with rt-PA in order to explore the optimal dose of rt-PA intravenous thrombolysis for the very elderly patients in Tianjin, China.

Patient’s Clinical Data

The clinical data of AIS patients aged ≥ 80 years with disabling deficits presenting within 4.5 hours after symptom onset who were treated in Nankai University Affiliated Tianjin Fourth Central Hospital from February 2019 to October 2021 were retrospectively analyzed. In the current study, after neurologists fully explaining the efficacy and safety of low-dose and standard-dose rt-PA on the AIS, the 2 doses of rt-PA were chosen by patients or first-degree relatives. Then the eligible patients were divided into two groups on the basis of dose of rt-PA: rt-PA low-dose group (receiving rt-PA intravenous thrombolysis, 0.6 mg/kg; maximum dose 60 mg, 10% as bolus over 1 min, 90% as infusion over 1 hour) and rt-PA standard-dose group (0.9 mg/kg; maximum dose 90 mg, 10% as bolus over 1 min, 90% as infusion over 1 hour).

Inclusion/Exclusion Criteria

The basic inclusion/exclusion criteria were based on the 2018 American Heart Association (AHA) and American Stroke Association (ASA) Guidelines for the Early Management of Patients With AIS within 4.5 hours from symptom onset [6]. Additional inclusion criterias include (a) age ≥ 80 years with a definite diagnosis of AIS; (b) first-ever AIS or recurrent AIS with baseline modified Rankin Scale (mRS) score of 0. Additional exclusion criterias include (a) hyperglycemia [> 400 mg/dL (> 22.22 mmol/L)]; (b) stroke mimics or transient ischemic attack; (c) patients presenting in an acute life-threatening medical conditions (such as severe acute respiratory failure, acute myocardial infarction, acute aortic dissection, and pulmonary embolism); (d)treated with surgery treatment (such as intra-arterial mechanical thrombectomy, drainage through cranial trephination or craniotomy and hematoma removal).

Data collection

Patient’s data were extracted from the database of stroke Center, including demographic data (age, gender), past medical history (hypertension, coronary heart disease, atrial fibrillation, diabetes mellitus, hyperlipidemia, prior stroke or transient ischemic attack, etc.); admission data recorded included National Institutes of Health Stroke Scale (NIHSS) scores, laboratory values (blood glucose, hemameba, blood platelet count, and serum creatinine, etc.), onset-to-needle time (defined as the time from symptom onset to rt-PA bolus administration) and door-to- needle time (defined as the interval between the time of patient arrival at the hospital and rt-PA bolus administration); medical therapy and IV thrombolysis data. Most of the patients were followed up face to face at the follow-up center on 90-day, and some patients were followed up at home or by telephone. All the data were collected and recorded by two physicians in the research group independently, and the accuracy of the data was checked by the research group.

Outcome measurements

The efficacy endpoint was favorable functional outcome (mRS score of ≤ 2 at 90 days). The short-term safety endpoints were intracerebral hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and fatal intracerebral hemorrhage (fICH; death due to ICH within 7 days). We defined sICH as the NINDS study did: any type of intracerebral hemorrhage on the imaging scan obtained 24 to 36 hours after treatment, with NIHSS score increase of ≥ 1 points from baseline or leading to death [7]. The long-term safety endpoint was death within 90 days.

Statistical analysis

The measurement data of normal distribution were expressed as mean ± standard deviation (SD), and inter-group comparisons of mean values were implemented by t test with two independent samples. The measurement data of the skewness distribution was provided as medians (interquartile range, IQR) and comparison was done using the Mann-Whitney U test. Categorical data were described by constituent ratio (%) or rate (%) and analyzed by χ² test or Fisher's exact analysis. Regarding the efficacy and safety, multiple logistic regressions were employed to derive unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). For the multivariate logistic regression analyses, the model 1 was performed without covariate adjustment, model 2 was adjusted for varying stroke severity. P < 0.05 was considered statistically significant.

Study population

A total of 343 patients aged ≥ 80 years with onset within 4.5 h were diagnosed. After excluding 35 cases of stroke mimics, 28 cases of transient ischemic attack, 45 cases of intra-arterial mechanical thrombectomy, 15 cases of incomplete observation indicators and 19 cases of lost to follow-up, 201 patients were finally enrolled. The baseline data including the common risk factors, the Trial of Org 10172 in acute stroke treatment (TOAST) classification and NIHSS scores were not significantly different for rt-PA low-dose group (n = 93) and rt-PA standard-dose group (n = 108). Baseline characteristics are detailed in Table 1.

Table 1

Baseline characteristics of rt-PA low-dose group and rt-PA standard-dose group
Baseline Variable	Overall (n = 201)	low-dose(n = 93)	standard-dose(n = 108)	P value
Age(years), median (IQR)	85.0(83.0,88.0)	85.0(83.0,90.5)	84.0(82.0,87.8)	.198
80–84,n(%)	96(47.8)	40(43.0)	56(51.9)	.411
85–90,n(%)	62(30.8)	30(32.3)	32(29.6)
≥ 90,n(%)	43(21.4)	23(24.7)	20(18.5)
Male,n(%)	95(47.3)	43(46.2)	52(48.1)	.787
Body mass (kg), mean (SD)	64.0 ± 10.7	64.2 ± 11.2	64.0 ± 10.6	.579
Past medical history,n(%)
Hypertension	142(70.6)	69(74.2)	73(67.6)	.306
Coronary artery disease	92(45.8)	42(45.2)	50(46.3)	.990
Atrial fibrillation	52(25.9)	27(29.0)	25(23.1)	.342
Diabetes mellitus	48(23.9)	25(26.9)	23(21.3)	.826
Dyslipidemia	43(21.4)	20(21.5)	23(21.3)	.971
previous cerebral infarction,n(%)	60(29.9)	30(32.3)	30(27.8)	.489
One time	42(20.9)	21(22.6)	21(19.4)	.553
Two times	10(5.0)	5(5.4)	5(4.6)
≥Three times	8(4.0)	4(4.3)	4(3.7)
Transient Ischemic Attack,n(%)	21(10.4)	9(9.7)	12(11.1)	.740
Smoking,n(%)	31(15.4)	13(14.0)	18(16.7)	.599
Alcohol,n(%)	9(4.5)	5(5.4)	4(3.7)	.736
clinical examination
Hemameba (10⁹/l), median (IQR)	7.1(5.8,8.9)	7.2(5.3,9.3)	7.0(6.0,8.9)	.604
Blood platelet count (10⁹/l), median (IQR)	185.0(153.0,185.0)	177.0(155.0,228.5)	192.5(156.0,228.0)	.745
Hemoglobin (g/L), mean (SD)	125.7 ± 22.4	123.9 ± 23.7	126.9 ± 21.8	.687
Blood glucose (mmol/L), median (IQR)	6.5(5.3,7.9)	6.9(5.9,8.1)	6.9(5.6,9.3)	.785
Serum creatinine (umol/L), median (IQR)	75.0(63.0,91.0)	79.0(65.0,92.5)	75.0(60.3,94.0)	.314
Blood ureanitrogen (mmol/L), median (IQR)	6.3(4.9,7.8)	6.3(4.9,7.8)	6.2(4.8,7.8)	.975
APTT (s), mean (SD)	37.4 ± 5.7	37.3 ± 5.6	37.5 ± 5.8	.866
PT (s), mean (SD)	13.6 ± 1.1	13.6 ± 1.0	13.5 ± 1.2	.183
TT (s), mean (SD)	17.9 ± 2.6	19.2 ± 2.4	18.2 ± 3.2	.460
INR (INR), mean (SD)	1.0 ± 0.1	1.0 ± 0.1	1.0 ± 0.1	.193
Onset-to-needle time (min), median (IQR)	120(98,179)	120(90,180)	120(120,160)	.248
Door-to-needle time (min), mean (SD)	40.0 ± 10.7	39.8 ± 10.0	39.9 ± 11.4	.208
Systolic pressure (mmHg), mean (SD)	162.8 ± 28.0	165.2 ± 28.5	164.0 ± 25.1	.166
Diastolic pressure (mmHg), median (IQR)	85(75,95)	82(75,93)	85(77,97)	.401
NIHSS score, median (IQR)	8(5,14)	7(5,13)	10(5,15)	.115
0–4(mild stroke) n(%)	41(20.4)	20(21.5)	21(19.4)	.537
5–10(moderate stroke) n(%)	76(37.8)	38(40.9)	38(35.2)
≥ 11(severe stroke) n(%)	84(41.8)	35(37.6)	49(45.4)
TOAST classification n(%)
Large vessel	76(37.8)	35(37.6)	41(38.0)	.981
Cardioembolism	41(20.4)	18(19.4)	23(21.3)
Small vessel	83(41.3)	39(41.9)	44(40.7)
mRS, modifed Rankin scale;NIHSS,National Institutes of Health Stroke Scale; INR,international normalized
Ratio;TOAST, Trial of Org 10172 in acute stroke treatment; rt-PA, recombinant-tissue plasminogen activator

Comparison of the effectiveness and safety among Low-dose versus standard-dose rt-PA groups

For the short-term safety outcome, the incidence of ICH, sICH and fICH in rt-PA low-dose group was all lower than that of rt-PA standard-dose group [8.6%(8/93) vs. 19.4%(21/108), 4.3%(4/93) vs. 10.2%(11/108), 1.1%(1/93) vs. 9.3%(10/108); unadjusted and adjusted P < .05]. For the long-term safety outcome, the death within 90 days was observed in 17 of 93 patients (18.3%) in rt-PA low-dose group and 24 of 108 patients (22.2%) in rt-PA standard-dose group (χ² = .478, P = .489; adjusted OR:0.824, 95% CI: 0.407–1.669, P = .591). For the efficacy endpoint, the proportion of patients with a favorable functional outcome of 0–2 on the mRS was observed in 52 of 93 patients (55.9%) in rt-PA low-dose group and 50 of 108 patients (46.3%) in rt-PA standard-dose group (χ² = 1.849, P = .174; adjusted OR:1.426, 95% CI: 0.811–2.507, P = .217). No clear differenc was observed on an ordinal analysis of the full range of scores on the mRS in low-dose versus standard-dose rt-PA group (all P > 0.05). The results are detailed in Table 2.

Table 2

Comparison of the effectiveness and safety among Low-dose versus standard-dose rt-PA groups
Outcome,n(%)	low-dose (n = 93)	standard-dose (n = 108)	Model 1		Model 2
Outcome,n(%)	low-dose (n = 93)	standard-dose (n = 108)	χ²	P	OR	95%CI	P
favorable functional outcome at 90 days	52(55.9)	50(46.3)	1.849	.174	1.426	0.811–2.507	.217
Intracerebral hemorrhage	8(8.6)	21(19.4)	5.919	.015	0.348	0.140–0.865	.023
Symptomatic intracerebral hemorrhage	4(4.3)	11(10.2)	6.119	.013	0.238	0.064–0.880	.031
Fatal intracerebral hemorrhage within 7 days	1(1.1)	10(9.3)	6.470	.011	0.115	0.014–0.937	.043
Death within 90 days	17(18.3)	24(22.2)	0.478	.489	0.824	0.407–1.669	.591
mRS scores at 90 days			9.370	.154	0.910	−0.526−0.460	.895
0 (no symptoms at all)	23(24.7)	27(25.0)	0.000	.985	0.974	0.516–1.841	.936
1 (no significant disability despite symptoms)	9(9.7)	11(10.2)	0.014	.905	0.908	0.357–2.309	.838
2 (slight disability)	20(21.5)	12(11.1)	3.327	.068	2.018	0.919–4.429	.080
3 (moderate disability requiring some help)	10(10.8)	23(21.3)	3.453	.063	0.460	0.205–1.034	.060
4 (moderate-severe disability requiring assistance with daily living)	7(7.5)	7(6.5)	0.084	.772	1.137	0.382–3.386	.817
5 (severe disability, bed-bound and incontinent)	7(7.5)	4(3.7)	1.412	.235	2.150	0.607–7.621	.236
6 (death)	17(18.3)	24(22.2)	0.478	.489	0.786	0.392–1.577	.498
mRS, modifed Rankin scale

Stratification by stroke severity among two groups

Stratification by stroke severity, among mild, moderate, and serious groups, only moderate group was more likely to have a favorable functional outcome treating by low-dose rt-PA than that of standard-dose rt-PA (χ² = 4.653, P = .031) and without a higher risk of mortality (mRS score of 6; P = 1.000). The results are detailed in Table 3.

Table 3

Treatment effects on modified Rankin Scale (mRS) at 90 days by stroke severity
Outcome	favorable functional outcome n(%)				unfavorable functional outcome n(%)
Outcome	sum	0	1	2	sum	3	4	5	6
mild stroke group(NIHSS ≤ 4)
low-dose (n = 20)	16(75.0)	12(60.0)	3(15.0)	1(5.0)	4(20.0)	1(5.0)	1(5.0)	0(0.0)	2(10.0)
standard-dose(n = 21)	16(76.2)	16(76.2)	0(0.0)	0(0.0)	5(23.8)	3(14.3)	1(4.8)	0(0.0)	1(4.8)
P value	.758	.265	.107	.488	1.000	.606	1.000	-	.606
moderate stroke group(5 < NIHSS ≤ 10)
low-dose(n = 38)	29(76.3)	11(28.9)	5(13.2)	13(34.2)	9(23.7)	4(10.5)	3(7.9)	0(0.0)	2(5.3)
standard-dose(n = 38)	20(52.6)	7(18.4)	8(21.1)	5(13.2)	18(47.4)	12(31.6)	3(7.9)	2(5.3)	1(2.6)
P value	.031	.280	.361	.031	.016	.024	1.000	.493	1.000
severe stroke group(11 ≤ NIHSS)
low-dose(n = 35)	7(20.0)	0(0.0)	1(2.9)	6(17.1)	28(80.0)	5(14.3)	3(8.6)	7(20.0)	13(37.1)
standard-dose(n = 49)	14(28.6)	4(8.2)	3(6.1)	7(14.3)	35(71.4)	8(16.3)	3(6.1)	2(4.1)	22(44.9)
P value	.371	.137	.637	.721	.371	.799	.690	.030	.477
mRS, modifed Rankin scale; NIHSS, National Institutes of Health Stroke Scale

Stratification by age among two groups

Upon stratification by age groups, among 80–84, 85–90, and ≥ 90 age groups, only patients aged ≥ 90 years, a greater proportion of favorable functional outcomes was observed in rt-PA low-dose group (χ² = 4.368, P = .037), while there is also no statistically significant difference in the risk of mortality among the two groups (P = .236). The results are detailed in Table 4.

Table 4

Treatment effects on modified Rankin Scale (mRS) at 90 days by age groups
	favorable functional outcome n(%)					unfavorable functional outcome n(%)
	sum	0	1	2	sum	3	4	5	6
80–84 age group
low-dose(n = 40)	23(57.5)	10(25.0)	6(15.0)	7(17.5)	17(42.5)	3(7.5)	2(5.0)	5(12.5)	7(17.5)
standard-dose(n = 56)	31(55.4)	15(26.8)	10(17.9)	6(10.7)	25(46.4)	10(19.6)	2(3.6)	1(1.8)	12(21.4)
P value	.835	.844	.396	.034	.703	.097	1.000	.079	.634
85–90 age group
low-dose(n = 30)	16(53.3)	9(30.0)	1(3.3)	6(20.0)	14(46.7)	4(13.3)	3(10.0)	0(0.0)	7(23.3)
standard-dose(n = 32)	14(43.8)	10(31.3)	0(0.0)	4(12.5)	18(56.3)	7(21.9)	2(6.3)	2(6.3)	7(21.9)
P value	.622	.915	.484	.502	.450	.562	.667	.492	1.000
≥ 90 age group
low-dose(n = 23)	13(56.5)	4(17.4)	2(8.7)	7(30.4)	10(43.5)	3(13.0)	2(8.7)	2(8.7)	3(13.0)
standard-dose(n = 20)	5(25.0)	2(10.0)	1(5.0)	2(10.0)	15(75.0)	6(30.0)	3(15.0)	1(5.0)	5(25.0)
P value	.037	.669	1.000	.142	.037	.263	.650	1.000	.236
mRS, modifed Rankin scale

This study was motivated by our concern both the optimal dose of rt-PA and insights for stratification of AIS in the Chinese octogenarian patients. In our study, there were no significant differences in the 90 d outcomes of favorable functional outcome or death between low-dose and standard-dose rt-PA-treated patients with AIS. These results are similar to previous ENCHANTED trial [4] concerning the treatment effects of low-dose versus standard-dose rt-PA on efficacy and long-term safety outcome. In terms of short-term safety outcome, our results are not entirely consistent with the ENCHANTED trial [4]. In fact, the ENCHANTED trial [4] showed the incidence of sICH (NINDS study criteria) in octogenarian patients was not significantly higher in the standard-dose group (8.2% in the low-dose group vs 8.3% in the standard-dose group; adjusted OR:0.98, 95% CI: 0.51–1.89, P = .76). Our results show that low-dose rt-PA had lower sICH (4.3% in the low-dose group vs 10.2% in the standard-dose group; adjusted OR:0.238, 95% CI: 0.064–0.880, P = .031). In our study, the higher incidence of sICH than ENCHANTED trial [4] may be mainly related to the more serious stroke severity, which is the most important factor affecting ICH [8]. Secondly, due to ethnic differences in coagulation and fibrinolysis responses [9, 10, 11], such as in the altered functions of fibrinogen and factor XII [5],Asian AIS patients are at higher risk for ICH than non-Asian AIS patients after intravenous thrombolytic therapy, especially performed with standard-dose rt-PA. Finally, due to different physical and vascular risk factors, Asian AIS patients have a higher risk of ICH than non-Asian patients [12].

In addition to the lower incidence of intracranial hemorrhage, we also found two unique advantages in stratified studies with low doses rt-PA compared to previous studies about Asian very elderly [13] and non-elderly AIS patients [14, 15, 16]. The ENCHANTED trial [4] did not have a pooled analysis of favorable functional outcome (mRS score of ≤ 2) on day 90 after stroke onset in patients aged ≥ 90 years or moderate stroke defined as baseline NIHSS of 5–10. No studies and published literature have specifically investigated such advantages. At present, the exact mechanism of these two advantages are not clear, and may be related to the following hypothesis. Low doses of rt-PA may be sufficient to break down thrombus in geriatric patients or moderate stroke, open infarct-related artery to save the ischemic penumbra, and reduce the risk of intracranial hemorrhage, which is the most serious complication of rt-PA intravenous thrombolysis, especially in patients older than 90 years. based on this hypothesis, according to the low-dose (0.6 mg/kg), maximum dose 60 mg of rt-PA might be enough for Chinese geriatric AIS patients with an optimal risk-benefit balance.

In addition to these two unique findings, there are two reasons that limit the widely adoption of standard-dose rt-PA in Tianjin, China. The ICH risk and the drug high cost are major obstacles [12]. In clinical practice, neurologists should discuss the risk of ICH of different doses of rt-PA with patients and their families before intravenous thrombolytic therapy. According to the data of our stroke center, 32.5% of geriatric AIS patients refuse to receive intravenous thrombolytic therapy due to fear of ICH, while 46.7% of geriatric AIS patients prefer low-dose rt-PA in view of lower risk of sICH and fICH. From public health and socioeconomic viewpoint, standard-dose rt-PA treatment can increase economic burden, since a greater proportion of geriatric AIS patients will experience moderate to severe disabilities or be bedridden for the rest of their lives due to higher ICH. Those patients will also require further post-acute stroke care in nursing homes, which represents increasing costs of post-acute stroke care due to increased stroke severity [17]. In order to promote rt-PA intravenous thrombolytic therapy in in elderly patients and further reduce the comprehensive cost, we recommend low-dose rt-PA intravenous thrombolytic therapy for geriatric AIS patients. This result goes with Zhao G et al who stated that low-dose rt-PA reduced the financial burden on patients and saved valuable medical resources, which might be more suitable for Chinese people [16].

There were some limitations in the current study.

Firstly, This study was conducted in a single city and a single center in northern China. Due to the characteristics of local population, the selective bias of enrolled patients was increased. Secondly, this study was retrospective, and there was a recall bias in baseline data. Thirdly, the sample size was relatively small, and the obtained findings should be verified in future larger sample studies.

In summary, in a group of geriatric AIS patients from Tianjin, China, who were eligible for thrombolysis reperfusion therapy, a dose of rt-PA of 0.6 mg/kg was not shown to be noninferior to the standard dose of 0.9 mg/kg with respect to the primary outcome of death and favorable functional outcome at 90 days. In our study population, a dose of 0.6 mg/kg of rt-PA was associated with a lower ICH and sICH complications. According to risk/benefit ratio for patients aged ≥ 90 years or with moderate AIS, low-dose rt-PA, namely 0.6 mg/kg maybe the optimal dose. Confirmation of the results through multicentre, prospective, randomised trial is required.

Authors' contributions

Study concept and design: YWG, XC. Data acquisition and analysis:QH, XML, HGF, QL, LZ, CHW, HXW. Manuscript drafting and revising: YWG, XC,YHD, LJW. All authors critically reviewed the manuscript and agreed on this final version to be submitted to the journal.

Ethics approval and consent to participate

This study was approved by the Ethical Committee of Tianjin Fourth Central Hospital. The study was considered observational and not interventional by the Ethical Committee.

Acknowledgments

No funds, grants, or other support was received.

Competing interests

The authors declare no conflict of interest.

Author details

¹Department of Neurology, Nankai University Affiliated Tianjin Fourth Central Hospital, No. 3, Zhongshan Road, Tianjin 300143, People's Republic of China

²Department of medical department, Baoding xu shui district people’s hospital, No. 29, Zhenxing East Road, Baoding 072550, Hebei province, People's Republic of China

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Low-dose versus standard-dose recombinant tissue plasminogen activator in the very elderly patients with acute ischaemic stroke: a single-center study in Tianjin, China

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Abstract

Introduction

Patients And Methods

Patient’s Clinical Data

Inclusion/Exclusion Criteria

Data collection

Outcome measurements

Statistical analysis

Results

Study population

Comparison of the effectiveness and safety among Low-dose versus standard-dose rt-PA groups

Stratification by stroke severity among two groups

Stratification by age among two groups

Discussion

Conclusions

Declarations

References

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