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ORIGINAL ARTICLE
Year : 2020  |  Volume : 13  |  Issue : 5  |  Page : 437-440  

Our experience with stroke thrombolysis at a tertiary care center in South India


1 Department of Neurology, Kakatiya Medical College and MGM Hospital, Warangal, Telangana, India
2 Department of Medicine, Kakatiya Medical College and MGM Hospital, Warangal, Telangana, India

Date of Submission25-Jun-2019
Date of Decision26-Oct-2019
Date of Acceptance26-Oct-2019
Date of Web Publication7-Sep-2020

Correspondence Address:
Veeramalla Madhavarao
Department of Neurology, Kakatiya Medical College and MGM Hospital, Warangal, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_181_19

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  Abstract 


Introduction: Intravenous (IV) thrombolysis is the cornerstone of the treatment of acute ischemic stroke in modern stroke era. Alteplase, also known as recombinant tissue plasminogen activator, is currently the only approved drug for IV thrombolysis worldwide and is used for the treatment of acute ischemic stroke. Objective: The objective was to study the clinical efficacy and safety of IV thrombolysis with alteplase in acute ischemic stroke. Materials and Methods: We consecutively enrolled acute ischemic stroke patients who underwent IV thrombolysis with alteplase from October 2017 to May 2018. Primary clinical efficacy outcome was defined as an improvement in the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h. The secondary clinical efficacy outcome was the favorable outcome on the modified Rankin scale at 90 days, which is defined as a score of 0 or 1. The safety endpoints were death rate at 90 days and symptomatic intracranial hemorrhage (SICH). Results: The mean NIHSS scores at baseline and 24 h were 13.56 (±4.56) and 9.92 (±6.13), respectively, the difference being statistically significant (P < 0.001). In this study, 15 patients (60%) met the primary clinical efficacy outcome, and the same number achieved the secondary clinical efficacy outcome. Three patients (12%) developed SICH but without any deaths.
Conclusion: This study confirms the efficacy and safety of alteplase for stroke thrombolysis in our clinical setting.

Keywords: Acute ischemic stroke, alteplase, thrombolysis


How to cite this article:
Madhavarao V, Mohammed O, Valupadas C. Our experience with stroke thrombolysis at a tertiary care center in South India. Med J DY Patil Vidyapeeth 2020;13:437-40

How to cite this URL:
Madhavarao V, Mohammed O, Valupadas C. Our experience with stroke thrombolysis at a tertiary care center in South India. Med J DY Patil Vidyapeeth [serial online] 2020 [cited 2020 Sep 26];13:437-40. Available from: http://www.mjdrdypv.org/text.asp?2020/13/5/437/294344




  Introduction Top


Stroke is one of the leading causes of disability and death in India. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator remains a cornerstone in the treatment of acute ischemic stroke. It was first approved for use within 3 h of the onset of acute ischemic stroke based on the observations of the National Institute of Neurological Disorders and Stroke (NINDS) study.[1] Subsequently, European Cooperative Acute Stroke Study III (ECASS III) trial showed improved outcomes for carefully selected patients treated 3–4.5 h after a stroke.[2] In India, the magnitude of stroke thrombolysis has increased significantly over the past few years;[3],[4],[5] however, the rate of thrombolysis still remains low. Besides, stroke thrombolysis is mainly available in major corporate sector hospitals and apex government health institutes. One major constraint to the wide availability of stroke thrombolysis treatment is the high cost of alteplase, which is the gold standard thrombolytic agent for stroke. The government's initiative resulted in free procurement of alteplase at our government tertiary care hospital. Consequently, we analyzed the outcome of stroke patients thrombolysed with alteplase at our center; thus assessing the efficacy and safety of IV thrombolysis with alteplase in this region.


  Materials and Methods Top


The present study was a prospective observational study which was conducted from June 2017 to May 2018. During this period, we enrolled all the ischemic stroke patients who underwent thrombolysis with alteplase. The “Institutional Ethics Committee” approved the study protocol, and a written informed consent was obtained from all the study participants.

Inclusion and exclusion criteria

All patients with age of ≥18 years were diagnosed to have acute ischemic stroke after ruling out hemorrhage on noncontrast computed tomography (CT) brain with the National Institute of Health Stroke Scale (NIHSS) score >4 and a modified Rankin Scale (mRS) score of ≤2 preceding the onset of stroke. We have followed the same exclusion criteria as adopted in the NINDS study.[1]

Thrombolytic drug administration

Alteplase was administered within 4.5 h of the stroke onset. Informed consent was obtained in all cases after discussing benefits and the risk of a hemorrhagic event associated with thrombolytic therapy. The administered dose of alteplase was 0.9 mg/kg body weight, the maximum dose being 90 mg. About 10% of the total dose was given as IV bolus, whereas the remaining 90% was given as infusion over 1 h.

Outcomes

The primary clinical efficacy outcome was defined as the proportion of patients achieving significant early neurological recovery, with an improvement of 4 or more points on the NIHSS score at 24 h. Secondary clinical efficacy outcome was defined as a favorable outcome on disability assessment at 90 days, with a mRS score of 0 or 1. The safety end points were mortality rate at 90 days and symptomatic intracranial hemorrhage (SICH).

Clinical assessment

All patients who presented within the window period with symptoms suggestive of stroke were assessed by an emergency physician. After thorough history, clinical examination, calculation of NIHSS score, and premorbid mRS score, blood samples were drawn for standard laboratory tests, and capillary blood glucose estimation was done. A noncontrast CT scan of the brain was performed on an emergency basis to rule out intracranial hemorrhage as a cause of stroke. Patients fulfilling the standard inclusion and exclusion criteria were then thrombolysed according to the abovementioned protocol. Patients' vitals were continuously monitored for 24 h following thrombolysis. Any patient who had neurological worsening during the post thrombolysis period was urgently shifted for CT scan of the brain to rule out SICH. Further, all thrombolysed patients underwent repeat brain imaging 24 h after thrombolysis. NIHSS score estimation was done again at 2 h and 24 h following thrombolysis, whereas mRS score was reassessed at 7 and 90 days following thrombolysis.

Statistical analysis and variables involved

Patient's comorbid conditions, vital data, demographic data, details of clinical examination including blood investigations and brain imaging details, NIHSS, and mRS scores were recorded. Time variables such as symptom-to-door time, door-to-imaging time, and door-to-needle time were noted. The software used for statistical analysis was “SPSS version 16.0” (SPSS Inc., Chicago, IL, USA).


  Results Top


A total of 25 patients underwent IV stroke thrombolysis with alteplase during the study period. The mean age was 53 years. Males accounted for 92% (23/25) of patients, whereas females accounted for the rest 8% (2/25). Common risk factors were hypertension and dyslipidemia present in 68% (17/25) and 48% (12/25) of patients, respectively. Strokes in the territory of the right middle cerebral artery represented 72% of cases. The mean time to the first medical contact after the onset of symptoms was 147.2 min. The average “door-to-treatment” time or the time between hospital admission and the beginning of the injection of fibrinolytic treatment was 73.4 min. The mean NIHSS score at baseline was 13.56 (±4.56) and at 24 h was 9.92 (±6.13). The median mRS score at baseline was 4 and at 90 days was 1. [Table 1] shows the baseline characteristics of the patients included in the study.
Table 1: Baseline characteristics of 25 patients thrombolysed with alteplase

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Outcome analysis

In our study, the primary outcome, i.e., improvement of 4 or more points on the NIHSS score over 24 h was observed in 60% (15/25) patients. This difference between NIHSS scores at baseline and at 24 h was found to be statistically significant (P < 0.001). Attainment of secondary outcome, i.e., median mRS score of 0 or 1 over a period of 90 days was observed in 60% (15/25) patients; and the difference between the median mRS score at the baseline and at 90 days was found to be statistically significant (P < 0.001). About 12% (3/25) of patients developed SICH as an adverse event, but no deaths were reported in our study during the follow-up period of 90 days. [Table 2] shows the outcome analysis.
Table 2: Outcome analysis

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  Discussion Top


In India, over 1.5 million strokes occur every year, and it is the second leading cause of death. The annual incidence rate was between 13 and 124 strokes/100,000 persons.[3] Despite this, the rate of stroke thrombolysis is very less in our country more so in our local region of Telangana. Common barriers to stroke thrombolysis are failure to recognize stroke symptoms, unawareness about stroke as an emergency, unawareness about thrombolysis among patients or relatives, and transport delay. The present study reconfirmed the efficacy and safety profile of alteplase in acute ischemic stroke, as observed in other recent studies.[1],[2] The mean age of patients who underwent IV thrombolysis in our study was relatively less, i.e., 53 years when compared to other studies such as NINDS study in which the mean age was 68 years, and ECASS III study in which mean age was 64.9 years.

Incidence of hypertension in our study (68%) was similar to other studies on alteplase-NINDS study (66%), ECASS III (62.4%). In our study, the primary clinical efficacy outcome of improvement of 4 or more points on the NIHSS score over 24 h was observed in 60% (15/25) of patients, and this difference is statistically significant (P < 0.001).

About 60% (15/25) of patients attained a secondary outcome, i.e., median mRS score of 0 or 1 over a period of 90 days. This improvement of primary and secondary outcomes in our study was in accordance with previous studies on alteplase.

The rate of SICH in our study of 12% (3/25) appears to be higher when compared to other studies such as NINDS study in which the rate of SICH was 6.8% and ECASS III study in which the rate of SICH was 2.4%. This high-appearing SICH rate could be attributed to the relatively small sample size in our study when compared to other studies. No patients died in our study during the follow-up period of 90 days which was a better outcome compared to NINDS study in which mortality was 17% and ECASS III study in which mortality was 7.7%.

Our study confirms the benefits of alteplase as an effective and safe agent for IV thrombolysis in acute ischemic stroke.

Limitations

The study was conducted in a small number of patients, and the findings need to be confirmed with a larger sample size. Our study is a single-arm study with alteplase; however, a randomized comparison with a control group is required to obtain a realistic data for our patients. We performed IV thrombolysis within 4.5 h of the symptoms onset, however, the benefits need to be confirmed in the extended time window of 6 h, as observed in the Third International Stroke Trial.[6]


  Conclusion Top


IV thrombolysis is still the initial modality of the management of acute ischemic stroke patients who present within the window period. Focus should be on stroke awareness programs to make people understand the importance of rushing to a stroke facility immediately after the onset. Alteplase is a safe and efficacious agent for stroke thrombolysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7.  Back to cited text no. 1
    
2.
Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317-29.  Back to cited text no. 2
    
3.
Pandian JD, Sudhan P. Stroke epidemiology and stroke care services in India. J Stroke 2013;15:128-34.  Back to cited text no. 3
    
4.
Durai Pandian J, Padma V, Vijaya P, Sylaja PN, Murthy JM. Stroke and thrombolysis in developing countries. Int J Stroke 2007;2:17-26.  Back to cited text no. 4
    
5.
Pandian JD, Sethi V, Dhillon R, Kaur R, Padala S, Chakravorty R, et al. Is intravenous thrombolysis feasible in a developing country? Cerebrovasc Dis 2005;20:134-6.  Back to cited text no. 5
    
6.
IST-3 Collaborative Group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): A randomised controlled trial. Lancet 2012;379:2352-63.  Back to cited text no. 6
    



 
 
    Tables

  [Table 1], [Table 2]



 

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