Acute ischemic stroke and the golden hour: Critical updates

Prehospital care

Prompt recognition of stroke symptoms is crucial for obtaining timely medical care. However, awareness of stroke warning signs and risk factors remains largely poor. Stroke education campaigns should be tailored to emphasize the early recognition of stroke symptoms and the urgency of seeking immediate emergency care (class of recommendation [COR]-I, level of evidence [LOE]-B-NR).^[17] Further, to reinforce stroke identification, the use of prehospital stroke screening tools by Emergency Medical Services personnel is recommended (COR-I, LOE-B-NR).^[17] Delays in transport to the target hospital, preferably the closest healthcare facility able to administer recombinant tissue-type plasminogen activator (rtPA, alteplase), should be minimized through pre-arrival notification, allowing appropriate hospital resources to be mobilized before the patient’s arrival (COR-I, LOE-B-NR).^[17]

Over the past few years, numerous screening tools have been introduced to facilitate the rapid identification of acute stroke in prehospital settings. These include the Cincinnati Prehospital Stroke Scale, Face, Arm, Speech, Time (FAST), Balance, Eyes, FAST (BEFAST), Los Angeles Prehospital Stroke Screen, Melbourne Ambulance Stroke Screen, Emergency Medical Stroke Assessment, etc. Among these scales, the FAST and BEFAST provide the highest diagnostic accuracy and are also linked to improved outcomes [Figure 1].^[18,19]

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Figure 1:

BEFAST (balance, eyes, face, arm, speech, and time) and FAST (Face, arm, speech, and time) screening tools for rapid identification of acute stroke.

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The golden hour workup for AIS

The primary goal of triage and the initial assessment following acute stroke is to stabilize the airway, breathing, and circulation. Following this, a brief and focused neurological assessment is warranted to determine whether the presenting features are consistent with acute stroke and, to know whether the patient is eligible for IVT with rtPA to treat AIS. To optimize the AIS workup, the National Institute of Neurological Disorders and Stroke has established time targets for critical actions during the golden hour [Table 2].^[20] The time of symptom onset is defined as the time when the patient was “last seen normal” without the signs and symptoms of the current stroke. The use of a stroke severity rating scale, preferably, the NIHSS [Table 3],^[17,21] is recommended (COR-I, LOE-BNR) to quantify the degree of neurological deficit, facilitate communication, help identify patients for fibrinolytic or mechanical intervention, allow objective measurement of changing clinical status, and identify those at higher risk for complications such as ICH.^[17] All patients with suspected acute stroke should receive emergency brain imaging evaluation on their first arrival at a hospital before initiating any specific therapy to treat AIS (COR-I, LOE-A).^[17] Noncontract computed tomography (NCCT, COR-I, and LOE-A) or magnetic resonance (MR, COR-I, and LOE-BNR) imaging are both effective in excluding ICH before IV alteplase administration.^[17] However, MR imaging (MRI) is time-consuming and the precise sequences must be determined on a case-by-case basis. In patients who awake with stroke or have unclear time of onset >4.5 h from baseline or last known well, MRI to identify diffusion-positive fluid-attenuated inversion recovery–negative lesions can be useful for selecting those who can benefit from IV alteplase administration within 4.5 h of stroke symptom recognition (COR-IIa and LOE-B-R).^[17]

The benefit of IV alteplase therapy is time-dependent, and treatment should be initiated as quickly as possible (COR-I and LOE-A). Only the assessment of blood glucose must precede the initiation of IV alteplase in all patients (COR-I and LOE-B-NR).^[17] Baseline electrocardiographic (COR-I and LOE-B-NR) and troponin (COR-I and LOE-C-LD) assessments are recommended in patients presenting with AIS but should not delay initiation of IV alteplase. The same holds true for international normalized ratio, activated partial thromboplastin time, and platelet count.^[17]

IVT

IV alteplase is the first US Food and Drug Administration (FDA) approved drug for intravenous thrombolysis in AIS. Unless contraindicated [Table 4],^[17] IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 min with initial 10% of dose given as bolus over 1 min) is recommended for selected patients who can be treated within 3 h of ischemic stroke symptom onset or patient last known well or at baseline state (COR-I and LOE-A).^[17] However, the same regimen is also recommended for selected patients who can be treated within 3 and 4.5 h of ischemic stroke (COR-I and LOEB-R). These include patients ≤80 years of age, without a history of both diabetes mellitus and prior stroke, NIHSS score ≤25, not taking any oral anticoagulants, and without imaging evidence of ischemic injury involving more than one-third of the middle cerebral artery (MCA) territory.^[17] Patients eligible for IV alteplase should receive it even if EVT is being considered (COR-I and LOE-A).^[17] It is important to remember that for otherwise eligible patients with mild non-disabling stroke symptoms (NIHSS score 0–5), IV alteplase is not recommended for patients who could be treated within 3 h (COR III: No Benefit, LOE: B-R) or 4.5 h (COR III: No Benefit, LOE: C-LD) of ischemic stroke symptom onset or patient last known well or at baseline state.^[17] These recommendations align with the European Stroke Organization guidelines on IVT for AIS.^[22]

Physicians should be prepared to treat potential emergent adverse effects during and after IVT, including bleeding complications and angioedema that may cause partial airway obstruction (COR I, LOE: B-NR).^[17] Infusion should be promptly discontinued and a NCCT scan should be immediately obtained to exclude ICH if there is any new-onset severe headache, acute hypertension, nausea, vomiting, and/or worsening of neurologic status.^[23] Patients should be admitted to an intensive care unit since continued hemodynamic and neurologic monitoring is needed for 24 h post-infusion. Standard post rt-PA blood pressure (BP) monitoring is recommended every 15 min for 2 h, every 30 min for 6 h, and hourly for the remainder of the 24 h after treatment with rt-PA.^[17] Antiplatelet or anticoagulation therapy and invasive procedures should be withheld during the subsequent 24 h. An immediate neurosurgical consultation should be initiated during a post-rt-PA hemorrhage. Placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters should preferably be delayed unless necessary.^[17] The exact time frame is not defined; however, their placement should not delay the initiation of IV alteplase.

Tenecteplase, a genetically modified variant of alteplase, is gaining widespread use in the treatment of AIS and received FDA approval in March 2025. Intravenous tenecteplase in a single bolus dose of 0.25 mg/kg (maximum 25 mg) may be considered a reasonable alternative to IV alteplase for IVT (COR-IIb, LOE-B-R).^[17] A recent meta-analysis that included 11 randomized controlled trials (RCTs) comprising a total of 3788 patients found a similar safety profile between tenecteplase 0.25 mg/kg and alteplase while showing that tenecteplase is superior to alteplase regarding excellent functional outcome and reduced disability at 3 months.^[24] The results of this meta-analysis echo the findings of a few other meta-analyses published recently.^[25-27] The pertinent advantages of tenecteplase over alteplase include single bolus administration due to its longer half-life (22 vs. 4 min for alteplase), 15-fold higher specificity for fibrin and an 80-fold decreased binding affinity to plasminogen activator inhibitor-1.^[28]

EVT

EVT with or without IVT in large vessel occlusions (LVOs) can be considered within 0–6 h (the 1^st h being golden hour) either with a stent retriever (COR-I and LOE-A) or direct aspiration (COR-I and LOE-B-R) technique if the patients meet the following criteria: ^[17]

1. Prestroke mRS score of 0–1

2. Causative occlusion of the internal carotid artery (ICA) or MCA segment 1 (M1)

3. Age ≥18 years

4. NIHSS score of ≥6

5. Alberta stroke program early computed tomography score (ASPECTS) of ≥6

6. Treatment can be initiated (groin puncture) within 6 h of symptom onset.

Further, the benefits of EVT using stent retrievers may also apply to patients who can begin treatment within 6 h of symptom onset and meet specific criteria. These criteria include a pre-stroke mRS score greater than 1, an ASPECTS score below 6, or an NIHSS score under 6, with a confirmed occlusion of the ICA or proximal MCA (M1) (COR-IIb and LOE-B-R) or anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries (COR-IIb and LOE-C-LD).^[17] The four recent trials (Rescue-Japan LIMIT Trial, ANGEL-ASPECT Trial, SELECT 2 Trial, and TENSION Trial) have shown that EVT with or without IVT even in patients with large ischemic strokes (ASPECTS Score 3–5, average core volume >50 mL) is associated with improved functional outcome, quality of life, and overall survival.^[29-32] The discussion on EVT within the 6-–24-h therapeutic window is beyond the scope of this narrative update.

The technical objective of EVT should be to achieve reperfusion with an mTICI grade 2 b/3 angiographic result, optimizing the likelihood of a favorable functional clinical outcome (COR-I and LOE-A).^[17]

BP management

During the hyperacute phase of AIS, it is crucial to continuously monitor BP since extremes of BP are linked to poor outcomes.^[23] Hypotension and hypovolemia should be corrected to maintain systemic perfusion levels necessary to support organ function (COR-I and LOE-C-EO).^[17] Hypertension is not uncommon in patients with AIS and is attributable to multiple factors, such as chronic hypertension, sympathetic surge, and disturbance in cerebrovascular autoregulation.^[33] Control of high BP is warranted before performing IVT or EVT due to the possibility of a higher risk of ICH following the procedures. It is recommended to reduce BP ≤185/110 mm Hg in both IVT (COR-I and LOEB-R) and EVT (COR-IIa and LOE-B-NR) eligible patients before the procedure. Following IVT or EVT, BP should be maintained at <180/105 mm Hg for at least the first 24 h. A recent meta-analysis published in 2024 which included 4 major RCTs encompassing 1559 participants found that standard BP control (systolic BP ≤180 mm Hg) during the first 24 h post-EVT for AIS with LVOs was associated with better functional outcomes as compared to intensive BP control (systolic BP <140 mm Hg). In safety outcomes, there was no significant difference in all-cause mortality, any ICH, symptomatic ICH, parenchymal hematoma type 2, and stroke recurrence.^[34] However, in patients with BP ≥220/120 mm Hg who do not receive IVT or EVT and have no comorbid conditions (concomitant acute coronary event, acute heart failure, aortic dissection, post fibrinolysis symptomatic intracranial hemorrhage, or preeclampsia/eclampsia) requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating treatment of hypertension within the first 48–72 h is uncertain. It might be reasonable to lower BP by 15% during the first 24 h after onset of stroke (COR-IIb, LOE-C-EO). There is no clear evidence on the best pharmacologic agent for lowering BP during the hyperacute period of AIS. Different drug options (labetalol, nicardipine, clevidipine, hydralazine, etc.) may be appropriate depending on the expertise of the clinician and the availability of the drug [Table 5].^[17]

Golden hour supportive management

Temperature

Both hypothermia and hyperthermia are linked to unfavorable outcomes following AIS. For that matter, induced hypothermia has not demonstrated any significant benefit in enhancing neurological outcomes after AIS (CORIIb and LOE-B-R). The cause of hyperthermia (temperature >38°C) should be promptly identified and addressed. In hyperthermic patients, antipyretic medications are recommended to reduce fever (COR-I, LOE- C-LD).^[17]

Antimicrobial therapy

The routine administration of prophylactic antibiotics has demonstrated effectiveness in lowering infection rates but no improvement in functional outcomes; therefore, it is not recommended (COR-III and LOE-A).^[17]

Anti-seizure therapy

Recurrent seizures following a stroke should be managed with anti-seizure medications based on the patient’s specific characteristics (COR-I and LOE-C-LD). However, the prophylactic use of anti-seizure drugs is not recommended (COR-III, no benefit; and LOE-C-LD).^[17]