Introduction

Acute ischemic stroke is the third most common cause of mortality after coronary artery diseases and cancer (1). It is a severe neurological problem that ranks first worldwide in terms of morbidity. Approximately 6 million people die due to a stroke and 17 million people have a stroke each year (2,3). Ischemic strokes constitute more than 85% of all strokes (4). In our country, this rate was reported to be 71% (5).

In the treatment of acute ischemic stroke, intravenous recombinant tissue plasminogen activator (iv r-tPA) is the only approved medical treatment option for patients admitted in the treatment window (6,7). Endovascular treatment is recommended in patients with major vascular occlusion (8). Unfortunately, the most important obstacle to these treatments is the limited duration. 1.9 million neurons are lost in every minute of the brain until reperfusion is achieved (9).

However, despite the efficacy of iv r-tPA in acute ischemic stroke patients iv r-tPA, due to numerous limiting factors, it has been reported that only 3.0-8.5% of patients with ischemic stroke were applied iv r-tPA (10-12). The aim of this study was to evaluate the iv r-tPA  and/or mechanical thrombectomy indications in the patients with acute stroke admitted to our emergency department and/or hospitalized at the neurology department and in case these treatments were not applied, to determine reasons why these treatments were not applied in our patients and to correct these issues.

Materials and Methods

Bursa Yüksek İhtisas Training and Research Hospital is a tertiary care hospital. In our hospital, periodic training on stroke is being provided to healthcare personnel since 4 years. A number of awareness programs have been organized to increase public awareness about stroke.

In our stroke centre, iv r-tPA was first administered to patients with acute ischemic stroke in 2016. Since 2017, mechanical thrombectomy is being performed in our hospital.

The study included 300 patients with accessible data who had been admitted to the emergency department of our hospital for the diagnosis of stroke and/or hospitalized in the neurology department due to stroke between January 2018 and June 2019. The study was approved by the ethics committee of Bursa Yüksek İhtisas Training and Research Hospital, decision numbered and dated: 2011-KAEK-25, 2019/06-28, and the requirement of informed consent was waived off because of the retrospective nature of the study. The patients with acute stroke were retrospectively examined with regards to demographic (age, sex) and clinical information (the time of stroke, admission time, risk factors for stroke, neurological examination findings, stroke severity, and radiological findings), whether iv r-tPA and/or mechanical thrombectomy treatment was applied, and the reasons why these treatments were not applied. Stroke severity at admission was determined using the National Institutes of Health Stroke Scale (NIHSS). In the case of wake-up strokes, the onset of the symptom was accepted as the last point in time when the patient appeared normal.

Statistical Analysis

The consistency of continuous variables to normal distribution was examined with the Kolmogorov-Smirnov test. According to the normality test result, continuous variables are expressed with mean, standard deviation, minimum and maximum values. Categorical variables were given as n (%) values as indicative statistics. SPSS (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.) program was used for statistical analysis.

Results

Of the 300 patients, 142 (47%) were females and 158 (52%) were males; all the patients had been admitted between January 2018 and June 2019 to the emergency department of our hospital with the diagnosis of stroke and/or hospitalized in the neurology department due to stroke.

The mean age of the patients was 68.11±13.15 years (34-94 years). The time between the onset of stroke symptoms and admission to the emergency department varied from 15 minutes to 10 days, and the mean time was 5 (0.42:420) hours. NIHSS scores ranged between 0 and 32. Of the 259 (86%) patients diagnosed with ischemic stroke, 11 (3.6%) and 30 (10%) were diagnosed with intracerebral haemorrhage and transient cerebral ischemic attack, respectively.

Total 137 (45%) patients had been admitted to the hospital in the first 1.5 hours; 53 (17%), between 1.5 and 3 hours; 24 (8%), between 3 and 4.5 hours; 54 (18%), between 4.5 and 24 hours; and 32 (10.6%), after 24 hours. A total of 214 (71%) patients had been admitted to the hospital within the first 4.5 hours; 58 (19%) of the patients admitted to the hospital during the window period had contraindications for iv r-tPA.

When the patients were evaluated in terms of risk factors of stroke, it was found that 191 (63%), 64 (21%), 86 (28%), 104 (34%), 78 (26%), 86 (28%), and 57 (19%) of the patients had hypertension, hyperlipidemia, coronary artery disease, Diabetes mellitus, were smokers, history of stroke, and history of atrial fibrillation, respectively.

There were 64 (21%) patients with NIHSS of ≥6 who could not reach the hospital within the treatment window.

Ninety-seven (32%) patients with NIHSS of ≥6 who had been admitted to the hospital in the first 4.5 hours (treatment window) were examined, and it was found that 27 of these patients underwent iv r-tPA, three underwent iv r-tPA and mechanical thrombectomy, and nine underwent only mechanical thrombectomy. Fifty-eight (19%) of the patients did not undergo iv r-tPA and/or mechanical thrombectomy due to contraindications (Table 1).

Of the 27 patients over the age of 80 years who had been admitted within the first 4.5 hours, eight underwent iv r-tPA, one underwent iv r-tPA and mechanical thrombectomy, and one underwent only mechanical thrombectomy.

Discussion

The license for the use of iv r-tPA in acute ischemic stroke was obtained in Turkey in 2006. Although the application of iv r-tPA in Turkey is not yet at the desired level, its use is gradually increasing (13). It has been shown that in the case of acute ischemic stroke, 15-minute decrease in the door-to-needle time leads to 5% decrease in mortality in iv r-tPA application (14).

It has been determined that the annual rate of stroke-related deaths has decreased by 34% in the 10-year period between 1997 and 2007 owing to the efforts conducted to combat stroke and the fact that treatments applied in the acute period are becoming increasingly common (15).

Unfortunately, previous studies have found the rates of patients treated with iv r-tPA to be far below the desired level owing to many factors (10-12), this is caused by different reasons in different countries (11,16).

Many patients are unable to reach the hospital within the treatment window. One of the most important reasons for the inability of patients to reach the hospital within the treatment window may be society’s low level of knowledge on this subject (17).

In terms of treatment window, in this study, 63% and 71% of the patients were admitted to the hospital within the first 3 hours and 4.5 hours, respectively. This ratio was found to be higher compared with that in previous studies (18-23). This may be the result of the training and awareness-raising efforts regarding acute stroke that have been conducted over the past 3 years for healthcare professionals and the public.

In our study, there were 64 (21%) patients with NIHSS of ≥6 who could not reach the hospital within the treatment window, missing the opportunity for acute stroke treatment. In other words, had these patients arrived within the appropriate timeframe, these treatments could have been applied. A significant portion of these delays was due to the prolonged examination times within the hospital. There were six (2%) patients who reached the hospital within the treatment window, but they could not receive treatment as the treatment period was exceeded by the time their tests were completed.

There were 97 (32%) patients with NIHSS of ≥6 who admitted to our hospital within the treatment window. Of these patients, 27 received iv r-tPA, three received iv r-tPA and mechanical thrombectomy, and nine received mechanical thrombectomy. Fifty-eight (19%) of the patients could not be treated due to contraindications.

iv r-tPA and/or mechanical thrombectomy were not considered for six of the patients who arrived at the appropriate time, because these patients had rapid recovery and no significant deficits remained. The administration of iv r-tPA is recommended for patients who improve noticeably but continue to have significant deficits (24,25).

It has been reported that iv r-tPA can be administered in aneurysms with a diameter of <10 mm (26). Thrombolytic therapy was not performed in one of our patients due to a giant aneurysm with a diameter of >10 mm in the intracerebral artery.

Although the risk of intracerebral haemorrhage is higher in elderly patients, the use of iv r-tPA is recommended in patients over 80 years old unless there are other exclusion criteria  (27,28). In nine patients, iv r-tPA was not administered due to the increased risk of intracerebral haemorrhage associated with advanced age and other accompanying risk factors. Of the 27 patients who were ≥80 years old and arrived at the hospital in the first 4.5 hours, eight received iv r-tPA, one received iv r-tPA + mechanical thrombectomy, and one received only mechanical thrombectomy.

Patients do not benefit adequately from iv r-tPA when they have a mobility-preventing disability that develops before the stroke. However, iv r-tPA is still recommended moderate disability or in patients who can remain standing with assistance (27-30). In our study, four bed-ridden patients were not treated due to their mobility-preventing disability.

Before initiating iv r-tPA treatment, blood pressure must be below 185/110 mmHg to reduce the risk of intracerebral haemorrhage (27,31). In five of our patients, iv rt-PA was not administered due to blood pressure that could not be reduced below 185/110 mmHg despite antihypertensive treatment.

Two patients did not receive iv r-tPA treatment due to warfarin use and an international normalized ratio (INR) value of >1.7. IV r-tPA is administered in patients using oral anticoagulants if their INR is <1.7 (31).

Study Limitations

The limitations of the present study include the limited number of patients, the inclusion of a single centre, and the lack of access to certain data owing to the retrospective nature of the study. This study investigated and presented the reasons why current treatment modalities for acute stroke treatment, such as thrombolytic treatment and mechanical thrombectomy, were not applied in some of our patients.

Conclusion

In our study, we determined that the most common reason for not applying iv r-tPA and mechanical thrombectomy treatments out of contraindications to patients was the fact that these patients could not reach the hospital within the treatment window and loss of time that occurred during the examinations and tests performed in the hospital.

To ensure the application of treatments, such as r-tPA and mechanical thrombectomy, which are life-saving and prevent disabilities, it is necessary to prepare algorithms in the hospital so that the processes after a patient is admitted to the emergency department can be managed rapidly.  Addressing these factors may increase the ratio of patients who can receive thrombolytic therapy or undergo mechanical thrombectomy.

Ethics

Ethics Committee Approval: The study was approved by the ethics committee of Bursa Yüksek İhtisas Training and Research Hospital, decision numbered and dated: 2011-KAEK-25, 2019/06-28.

Informed Consent: The requirement of informed consent was waived off because of the retrospective nature of the study.

Peer-review: Externally peer-reviewed.

Financial Disclosure: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.