Outcomes of endovascular treatment for acute ischaemic stroke in Mater Dei Hospital, Malta

Abstract

Introduction

The aim of this study was to assess the outcomes of endovascular treatment for acute ischaemic stroke in Mater Dei Hospital, Malta and compare them with international data.

Methods

A prospective review of all patients who underwent mechanical thrombectomy from 2015 to the end of 2019 was performed. Eligible patients had large vessel occlusion confirmed on computed tomography angiography. Demographical data, the National Institutes of Health stroke scale at presentation, endovascular procedure details and process times were analysed. The thrombolysis in cerebral infarction score was used to assess the degree of reperfusion. A thrombolysis in cerebral infarction score of 2b–3 was considered as successful recanalisation. Functional outcome (modified Rankin scale score) and mortality at 90 days were measured. Functional independence was defined as a modified Rankin scale score of 2 or less.

Results

A total of 132 patients underwent endovascular treatment, one patient was excluded due to incomplete data. The mean age was 71 (range 25–94) years, and the mean National Institutes of Health stroke scale at presentation was 14. Of the 131 patients treated, 69 received intravenous thrombolysis. Successful recanalisation (thrombolysis in cerebral infarction score 2b–3) was achieved in 80% of patients (105/131); 53% of patients (69/131) achieved functional independence at 90 days, with a mortality of 21% at 90 days. Symptomatic intracranial haemorrhage was recorded in 16 patients (12%) There was a statistical difference in the functional independence and mortality rate in favour of the successful recanalisation group.

Conclusion

Our data are consistent with a favourable clinical outcome after successful recanalisation. Service in Malta is achieving favourable outcomes for patients treated with mechanical thrombectomy for acute ischaemic stroke.

Aims

The main aim of this study was to assess the outcomes of endovascular treatment for acute ischaemic stroke (AIS) in Mater Dei Hospital, Malta and compare them with that of other international centres.

Introduction

Stroke is the second leading cause of death worldwide, responsible for about 11% of the world’s total deaths. ¹ Locally, AIS is the second leading cause of death, with a mortality rate of approximately 132 men and 102 women per 100,000, accounting for 8.3% of all deaths.^2,3

Malta has one acute general hospital, which provides acute stroke treatment. Mechanical thrombectomy was introduced in Malta in 2015, while the use of intravenous thrombolysis for AIS has been established as a service since 2010.

Throughout recent years, the use of endovascular treatment for AIS was fraught with controversy. In 2015, positive results were published, namely MR CLEAN, ⁴ ESCAPE, ⁵ EXTEND-IA ⁶ and SWIFT PRIME. ⁷ All of these trials showed that patients who underwent mechanical thrombectomy achieved better clinical outcomes compared with thrombolysis alone. The results were reproduced in another study in 2015, REVASCAT. ⁸ These studies shift the concern that mechanical thrombectomy is of no significant benefit over standard medical care, as was originally published in three earlier studies in 2013.^9–11 A meta-analysis of these studies, the HERMES collaboration, demonstrated that mechanical thrombectomy provides better outcomes to most patients, irrespective of patients’ demographics and medical history. ¹²

Materials and methods

This study is a prospective review of all patients who underwent mechanical thrombectomy as treatment for AIS since its introduction in Mater Dei Hospital, Malta, from 2015 to the end of 2019.

Data protection clearance was obtained as per local hospital guidelines. Patients’ data were inputted in the stroke and thrombectomy registries.

A total of 132 patients underwent endovascular treatment for AIS. One patient was excluded from the study due to incomplete data. Eligible patients had large vessel occlusion confirmed on computed tomography (CT) angiography. Intravenous (IV) thrombolysis was also administered to eligible patients (alteplase at a dose of 0.9 mg/kg).

The patients’ demographic data and National Institutes of Health stroke scale (NIHSS) at presentation were collected. Timings from onset of symptoms to endovascular treatment (arterial puncture), door to CT brain, and CT to puncture were calculated. Details of the endovascular procedure – occlusion site, stent retriever used, number of passes, thomboaspiration, tandem carotid stenting and degree of perfusion (using the thrombolysis in cerebral infarction (TICI) score) were recorded (Table 1). A TICI score of 2b–3 was considered as successful recanalisation.

Table 1.

Endovascular procedure details.

Endovascular technique	No. of patients
Stent retrieval device and size
Solitaire	122
No available data	9
4 × 20 mm	47
6 × 30 mm	75
Site of occlusion
Proximal ICA	18
Carotid terminus	1
MCA	20
M1 segment MCA	76
M2 segment MCA	9
ICA + MCA	5
Basillar	2
Thromboaspiration
No	107
Yes	21
No available data	3
Tandem carotid stent placement	10
No. of passes
0	1
1	58
2	27
3	10
4	16
5	9
6	2
7	1
No available data	7

ICA: internal carotid artery; MCA: middle cerebral artery.

All patients had brain imaging 24 hours post-thrombectomy, or earlier if there were signs of neurological deterioration. Symptomatic intracerebral haemorrhage (ICH) was defined as any intracranial bleed associated with an increase in the NIHSS score greater than 4 or death within 24 hours of treatment.

The modified Rankin scale score (mRS) at 90 days was used to assess functional outcome. Data were collected from either follow-up outpatient visits or via telephone consultations at 90 days post AIS. Functional independence was defined as mRS of 2 or less. Statistical analysis was performed with SPSS v24. Fisher’s exact tests were performed for significance. A P value of less than 0.05 was considered to be significant.

Results

Between June 2015 and December 2019, a total of 132 patients had mechanical thrombectomy, the majority performed in the most recent 2 years (Figure 1). One patient was withdrawn from the study due to incomplete data.

Figure 1.

Number of mechanical thrombectomy procedures.

The mean age of the patients was 71 (range 25–94) years, with a female (68:63) preponderance. In the majority of the cases, the onset of symptoms occurred between 08:00 am and 04:00 pm.

Demographics and process measures are presented in Table 2. The mean NIHSS at presentation was 14. In the absolute majority, endovascular treatment was performed for anterior circulation intracranial vessel occlusion.

Table 2.

Demographics, presentation and process times.

Demographics
Total no. of patients	131
Men	63
Women	68
Age (years)
Mean	71
Range	25–94
Presentation
NIHSS at presentation
Mean	14
Range	2–32
Affected side clinically
Right	65
Left	64
Other	2 – basilar occlusion
Onset of symptoms	No. of patients
00:00–08:00	39
08:01–16:00	48
16:01–23:59	34
Wake-up	4
Unknown onset	6
IV thrombolysis
Yes	69 (52.7%)
No	62 (47.3%)
Reasons for no thrombolysis
Onset >4.5 hours	5
On oral anticoagulation	22
Wake-up/unknown clear onset	10
Recent invasive procedure	6
Recent history of bleeding	1
Active malignancy	6
Head injury	2
Low NIHSS/rapidly improving	5
Other medical contraindications	5
Process times	Mean – mins
Door to CT	35 (range 5–218)
CT to puncture	78 (range 11–282)
Onset to puncture	199 (range 56 mins to 18.04 hours)

CT: computed tomography; IV: intravenous; NIHHS: National Institutes of Health stroke scale.

Intravenous thrombolysis was administered to 69 patients (52.7%). In the other 62 patients (47.3%), IV thrombolysis was contraindicated for various reasons (Table 2).

The mean time from door (time registered at the accident and emergency department) to CT brain was 35 minutes, the mean time from CT to puncture was 78 minutes, while the mean time from onset of symptoms to puncture was 199 minutes (Table 2).

Successful recanalisation (TICI 2b–3) was achieved in 80% of patients (105/131), with complete recanalisation in 73 patients (56%). Further details are shown in Figure 2.

Figure 2.

Modified Rankin scale score at 90 days.

Functional independence (mRS ≤2) at 90 days (Figure 2) was achieved in 53% of patients (69/131). Mortality at 90 days was 21% (28/131). Out of the 28 patients, the onset of stroke to death was less than 7 days in 13 patients (46%), the rest died within 30 days.

During follow-up imaging, 29 patients (22%) were found to have ICH. It was considered symptomatic in 16 patients (12%). Out of the 16 patients with symptomatic ICH, functional independence at 90 days was only achieved in one patient, while mortality at 90 days was 81% (13/16). The remaining three patients remained with significant neurological deficit and dependence (mRS 5). Using the Fisher’s exact test (P<0.0001), the difference in the clinical outcome between patients with symptomatic ICH and those without is considered to be statistically significant.

There was a shift in the distribution of the mRS score in favour of the successful recanalisation group, with 81% of patients (65/105) achieving functional independence at 90 days. In contrast, only 15% of patients (four out of 26) with unsuccessful recanalisation achieved functional independence (P<0.0001) (Table 3).

Table 3.

Comparison of clinical outcomes in the successful and unsuccessful recanalisation subgroups, with or without thrombolysis.

Subgroups	Total %, (no./total no.)	Functional independence (mRS <2) at 90 days %, (no./total no.)	sICH %, (no./total no.)	Mortality at 90 days %, (no./total no.)
Successful recanalisation (2b–3)	80.2% (105/131)	81.3% (65/105)	9.5% (10/105)	15.2% (16/105)
Unsuccessful recanalisation (0–2a)	19.9% (26/131)	15.4% (4/26)	23.1% (6/26)	46.2% (12/26)
TICI 0/1	12% (16/131)	1.5% (2/131)	1.5% (2/ 131)	6.9% (9/131)
2a	8% (10/131)	1.5% (2/131)	3.1% (4/131)	2.3% (3/131)
2b	24% (32/131)	16.0% (21/131)	1.5% (2/131)	5.3% (7/131)
3	56% (73/131)	33.6% (44/131)	6.1% (8/131)	6.9% (9/131)
Thrombectomy only	47.3% (62/131)	45.2% (28/62)	9.7% (6/62)	29.0% (18/62)
Thrombolysis + thrombectomy	52.7% (69/131)	59.4% (41/69)	14.5% (10/69)	14.5% (10/69)
Overall	131	52.7% (69/131)	12.2% (16/131)	21.4% (28/131)

mRS: modified Rankin scale score; sICH: symptomatic intracerebral haemorrhage; TICI: thrombolysis in cerebral infarction score.

This difference was also demonstrated in mortality rates, with a 15% (16/105) mortality rate in the successful recanalisation group and 46% (12/26) in the unsuccessful group (P=0.0022). On the other hand, the difference in the rate of symptomatic haemorrhage was not considered to be statistically significant (P=0.0886).

The mRS of patients who experienced a wake-up stroke or stroke with an unknown onset was also assessed. Out of 10 patients, four patients achieved functional independence at 90 days (40%). There was one patient with a mRS of 5 at 90 days, with a mortality of 40% (four/10).

These data also include the two posterior circulation strokes. One patient achieved a mRS of 2 while the other an mRS of 4 at 90 days. Both had successful recanalisation.

The difference in the outcomes between patients who also received IV thrombolysis compared to those in whom it was contraindicated are demonstrated in Table 2. None of the observed differences (clinical outcome, symptomatic ICH and mortality) met the criteria for statistical significance using Fisher’s exact test (P=0.1170, P=0.4363 and P=0.0550, respectively).

This study showed that functional independence is correlated with age, NIHSS at presentation, affected clinical side, recanalisation and symptomatic ICH.

Discussion

The main aim of this study was to assess the outcomes of endovascular treatment for AIS in Mater Dei Hospital, Malta and compare them with those of other international centres.

There is an exponential increase in the number of mechanical thrombectomy procedures performed per year over the past few years. This is mainly due to better education and stroke awareness, hence earlier hospital presentations and more trained and specialised healthcare professionals. In 2013, a stroke awareness campaign, ACT FAST, was launched locally. Also, a dedicated stroke nurse has been assigned since 2017.

Out of the 131 patients receiving endovascular treatment, 105 patients (80%) achieved successful recanalisation (TICI 2b–3). This compares well with the outcomes of other centres’ trials (Figure 3). Sixty-nine patients (53%) also managed to achieve functional independence at 90 days (mRS ≤2) with a mortality rate at 90 days of 21% (28/131). These outcomes also compare positively with other international centres (Figure 3).

Figure 3.

Head-to-head comparison of clinical outcomes between different stroke centres.

Recanalisation, key time intervals and clinical outcomes were also in line with the multisociety consensus quality improvement revised consensus statement for endovascular therapy of AIS ¹⁹ (Table 4). On the other hand, the local rate of symptomatic ICH was higher than that recommended in the quality improvement metrics (12% vs. ≤10%).

Table 4.

Summary of the suggested quality improvement metrics with comparison to local data.

	Quality improvement metrics	Locally
Key intervals, mean (mins)
Door to CT	30 mins or less	35 mins
CT to needle	110 mins or less	78 mins
Outcome metrics
TICI 2b–3	70% or more	80%
Post procedure outcome
Symptomatic ICH	10% or less	12%
Clinical outcome
mRS 0–2	30% or more	53%

CT: computed tomography; ICH: intracerebral haemorrhage; mRS: modified Rankin scale score; TICI: thrombolysis in cerebral infarction score.

In all of the mechanical thrombectomy procedures performed locally, Solitaire devices were used. In two trials published in 2012, SWIFT ²⁰ and Trevo 6, ²¹ second generation retrieval devices were shown to be superior to first generation devices.

The use of intravenous thrombolysis between 3 to 4.5 hours after the onset of symptoms was shown to improve the clinical outcomes of patients with AIS.^22,23 Despite the fact that those patients not receiving IV tissue plasminogen activator (tPA) were considered as ‘clinically disadvantaged’ due to their comorbidities and contraindications to thrombolysis, there was no significant difference in outcomes when compared to patients who received IV tPA together with endovascular treatment. Styczen et al. ²⁴ documented six cases in which mechanical thrombectomy was performed in patients with pre-interventional intracranial haemorrhage post-thrombolysis. The clinical outcome of these patients was poor and thus the benefit of thrombectomy in such a cohort remains very controversial. ²⁴

Given the favourable outcomes of patients who undergo mechanical thrombectomy for AIS, the next way forward is to develop ways to make its use more reasonable and safer in higher risk cohorts, such as pregnant women. ²⁵

All things considered, it can be concluded that the service in Malta is managing to achieve favourable outcomes for patients treated with mechanical thrombectomy for AIS. The service is still being developed and aims to achieve better outcomes to continue helping patients return back to their previous functional state.