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Can cerebral infarction in elderly patients be thrombolysis? See what the top issue has to say!

 Last Update: 2023-01-06
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*For medical professionals
only, can I have thrombolysis over 80 years old? Can I have thrombolysis over 90? As the population ages, the incidence of ischemic stroke is also increasing
.
Although the benefits of thrombolytic therapy in early acute ischaemic stroke are unquestionable, clinicians remain concerned about thrombolytic treatment decisions in older patients with ischaemic stroke
.

So, can elderly patients be treated with thrombolysis? How should thrombolysis be evaluated in older patients? This article summarizes several recent research progress and briefly analyzes several hot issues
of thrombolysis in the elderly.

Q1: Can elderly patients be treated with thrombolysis?

■ IST-3 study: The therapeutic range of alteplase can be extended to patients over 80 years of age

The third International Stroke Trial (IST3), initiated by the United Kingdom ^[1], included a total of 3035 patients in 156 hospitals in 12 countries, of which 1617 (53%)
were aged > 80 years.
In this study, patients were randomly assigned to 0.
9mg/kg alteplase thrombolysis group and control group, and the survival and independent survival (OHS score 0~2) at 6 months in the thrombolytic group and the non-thrombolytic group were compared
.
Studies have shown that older patients can benefit from intravenous thrombolysis (Figure 1).

Figure 1: Results of IST-3 studies show that > 80-year-old patients can benefit from intravenous thrombolysis ^[1].

■Meta-analysis: people over 80 years of age may benefit from intravenous thrombolysis with alteplase within 3 hours

A 2014 review published in Lancet in nine clinical trials (6756 patients with ischemic stroke treated with alteplase) (Figure 2) showed that people over 80 years of age still benefit from intravenous thrombolysis with alteplase within 3.
0 hours of onset ^[2].

Figure 2: Meta-analysis suggests that intravenous thrombolysis with alteplase within 3.
0 hours of onset is still beneficial in people over 80 years of onset ^[2].

■ Neurology: People over 80 years of age with stroke can still benefit from intravenous thrombolysis with alepplase within 3-4.
5 hours

In 2017, a study from the Karolinska Institute in Sweden compared the outcomes and risks
of intravenous thrombolysis within 3 hours and 3-4.
5 hours in patients over 80 years of age.
A total of 14240 patients with ischemic stroke with thrombolysis within 4.
5 h aged 80 years (3558 at 3~4.
5 h) were included in this study, and functional independence (mRS score 0~2), mortality and incidence of symptomatic intracranial hemorrhage (sICH) were compared between the two groups
.
The results showed that although the rate of symptomatic intracranial hemorrhage in the 3-4.
5 hour group was higher than that in the 3-hour group, the difference in treatment outcomes between the two groups was not obvious, and thrombolysis at 3-4.
5 hours also brought about improved
prognosis.
This shows that elderly patients should not reject intravenous thrombolysis in the time window (3~4.
5 h) just because of age when there are no contraindications (Figure 3) ^[3].

Figure 3: The rate of symptomatic intracranial hemorrhage in the 3-4.
5 hour group was higher than in the 3-hour group, but the difference in treatment outcomes between the two groups was not significant, and thrombolysis at 3 to 4.
5 hours also led to improved prognosis ^[3].

Q2: Can very elderly patients (over 90 years old) have thrombolysis?

■ TRISP study: patients with ischemic stroke over 90 years of age have no higher incidence of symptomatic intracranial hemorrhage after thrombolysis than younger patients, but have a higher risk of death and poor functional prognosis On October 14, 2022, a large multicenter study (TRISP) published online in the journal Stroke compared the 3-month symptomatic intracranial hemorrhage rate, mortality and poor functional prognosis (defined as mRS≤2 points before stroke with 3-month symptomatic intracranial hemorrhage between patients aged ≥90 years and 90 <years of age (defined as patients with mRS 2 points before stroke; or the difference in mRS before stroke ≥3 points of mRS 4~5 points after treatment)</b11>

Table 1: TRISP studies are based on general clinical data and outcomes for age groups ^[4].

Results showed that of the 16,974 eligible patients, 976 (5.
7%) were ≥ 90 years
of age.
Compared with patients aged < 90 years, patients aged ≥90 years</b11>

Q3: What is the advantage of tenecteplase vs altenecteplase in the treatment of elderly ischemic stroke patients?

■ NOR-TEST study: There was no difference
in the efficacy and safety of tenecteplase and alteplase in patients with ischemic stroke ≥ 80 years of age.

The NOR-TEST trial was a multicenter, randomized, open-label, blind endpoint phase 3 trial ^[5] conducted in 13 stroke units in Norway, with patients assigned to tenecteplase 0.
4 mg/kg or altenecteplase 0.
9 mg/kg
.

In this study, only patients aged ≥80 years were included in the analysis
.
The primary outcome was good functional outcomes (3-month mRS score of 0~1), and secondary outcomes were symptomatic intracerebral hemorrhage within 24~48h, death within 3 months, and significant improvement
in neurological function within 24h.

Figure 5: Primary and secondary outcomes of the NOR-TEST trial ^[5].

The results showed that there was no significant difference in the proportion of patients with good functional outcomes (mRS score of 0~1) after 3 months between the tenecteplase treatment group and the alteplase treatment group [56/130 (43.
1%) vs 57/143 (39.
9%); OR=1.
14，95%CI=0.
70~1.
85，p=0.
59]
。 There was no significant difference in the incidence of symptomatic intracerebral hemorrhage in the first 48 hours between the two groups (11 patients in the tenecteplase group, accounting for 8.
5%; There were 10 cases in the alteplase group, accounting for 7.
0%; OR=1.
23，95%CI=0.
50~3.
00，p=0.
65)
。 In addition, mortality within 3 months was 18 (14.
3%) in the tenecteplase group and 21 (15.
3%) in the altiplase group (see Figure 5).

Q4: What does the current guide say?

Within 3 to 4.
5 hours of onset, the efficacy and safety of intravenous thrombolysis in patients aged >80 years old were consistent with
those in patients aged <80 years.
In patients with a history of stroke and diabetes, intravenous thrombolysis with alepplase is as effective
as treatment within 3 hours of onset.
Therefore, compared with the 2014 version of the guidelines, the 2018 version of the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke has removed "age > 80 years"
from the relative contraindications.
The 2019 AHA/ASA Guidelines for the Early Management of Acute Ischemic Stroke recommends intravenous thrombolysis in older stroke patients as follows:

Patients aged ≥ 18 years and meeting other conditions, regardless of whether they are over 80 years old or younger than 80 years old, are also recommended for intravenous thrombolytic therapy with alepplase (class I recommendation, level A evidence).
3~4.
5h onset, in patients with acute ischemic stroke over 80 years old, the benefit of alteplase thrombolysis therapy is unclear (class II.
a recommendation, level B evidence).

The 2021 edition of the European Stroke Organization (ESO) Guidelines for Intravenous Thrombolysis of Acute Ischemic Stroke recommends the following for older stroke patients:

Intravenous alteplase thrombolysis
is recommended for patients with acute ischemic stroke < 4.
5 hours of onset and > 80 years of age.
(Certainty of evidence: high; Recommended level: Strong).

and expert consensus indicates: all nine experts recommend that age alone should not be a limiting factor for intravenous thrombolysis, even in other settings covered by this guideline (e.
g.
, stroke upon waking; ischaemic stroke lasting 4.
5 to 9 hours (time of onset is clear); CT or MRI core/perfusion mismatch; mild stroke with disabling symptoms).

References:

1.
Sandercock, P.
, 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(9834): p.
2352-63.

2.
Emberson, J.
, et al.
, Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.
Lancet, 2014.
384(9958): p.
1929-35.

3.
Ahmed, N.
, et al.
, Outcome after stroke thrombolysis in patients >80 years treated within 3 hours vs >3-4.
5 hours.
Neurology, 2017.
89(15): p.
1561-1568.

4.
Altersberger, V.
L.
, et al.
, Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.
Stroke, 2022.

5.
Thommessen, B.
, et al.
, Tenecteplase versus alteplase after acute ischemic stroke at high age.
Int J Stroke, 2021.
16(3): p.
295-299.

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