Comparison of Different Dosages of Alteplase in Atrial Fibrillation-Related Acute Ischemic Stroke After Intravenous Thrombolysis: A Nationwide, Multicenter, Prospective Cohort Study in Taiwan

Abstract

Background Insufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses. Methods and Results This multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk-scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non-AF group, the AF group exhibited a 2- to 3-fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35-3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study standards did not significantly differ between the AF and non-AF groups. In addition, the low-dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63-4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk-scoring tools. Conclusions Different alteplase dosages did not affect functional status at 90 days in the AF and non-AF groups. Thus, the adoption of low-dose alteplase simply because of AF is not recommended.

Keywords: acute stroke; atrial fibrillation; functional outcome; intravenous thrombolysis; symptomatic intracranial hemorrhage.

Figure 1. Flow diagram of the study.

ECASS indicates European Cooperative Acute Stroke Study; ICH, intracranial hemorrhage; mRS, modified Rankin Scale; NINDS, National Institute of Neurological Disorders and Stroke; SICH, symptomatic intracranial hemorrhage; SITS‐MOST, Safe Implementation of Thrombolysis in Stroke‐Monitoring Study; and TTT‐AIS, Taiwan Thrombolytic Therapy for Acute Ischemic Stroke.

Figure 2. Distribution of functional outcomes at 90 days.

The data set shows no differences in functional outcomes between the atrial fibrillation (AF) and non‐AF groups after adjustment for the THRIVE (Totaled Health Risks in Vascular Events) score (adjusted odds ratio [OR], 1.10 [95% CI, 0.49–1.29]). mRS indicates modified Rankin Scale.

Figure 3. The relationship between the THRIVE (Totaled Health Risks in Vascular Events) score and clinical outcomes.

AF indicates atrial fibrillation; ECASS, European Cooperative Acute Stroke Study; mRS, modified Rankin Scale; NINDS, National Institute of Neurological Disorders and Stroke; SICH, symptomatic intracranial hemorrhage; RR, relative risk; and SITS‐MOST, Safe Implementation of Thrombolysis in Stroke‐Monitoring Study.

Figure 4. The distribution of functional outcomes at 90 days for subgroups receiving different doses of alteplase subgroups.

The data set shows no significant differences in functional outcomes between the atrial fibrillation (AF) and non‐AF groups after adjustment for the THRIVE (Totaled Health Risks in Vascular Events) score in the low‐dose subgroup (adjusted odds ratio [OR], 1.19 [95% CI, 0.98–1.43]) and standard‐dose subgroup (adjusted OR, 0.87 [95% CI, 0.65–1.18]), and no interaction was observed between different doses of alteplase (P=0.2237). mRS indicates modified Rankin Scale.

Figure 5. The relationship between the THRIVEs (Totaled Health Risks in Vascular Event) score and clinical outcomes for the atrial fibrillation group treated with different doses of alteplase.

The zero‐inflated Poisson regression models were used to plot the relationship between the THRIVE score and symptomatic intracranial hemorrhage (SICH) by the ECASS II (European Cooperative Acute Stroke Study II) and the SITS‐MOST (Safe Implementation of Thrombolysis in Stroke‐Monitoring Study) standards. mRS indicates modified Rankin Scale; NINDS, National Institute of Neurological Disorders and Stroke; and RR, relative risk.

Figure 6. The distribution of each risk‐scoring system for atrial fibrillation (AF) and non‐AF groups.

ECASS II indicates European Cooperative Acute Stroke Study II; GRASP, Glucose, Race, Age, Sex, Pressure, Stroke Severity; HAT, Hemorrhage After Thrombolysis; SEDAN, the Blood Sugar, Early Infarct Signs and Hyperdense Cerebral Artery Sign, Age, and National Institutes of Health Stroke Scale; SITS‐SICH, the Safe Implementation of Treatment in Stroke‐Symptomatic Intracerebral Hemorrhage; SPAN‐100, Stroke Prognostication Using Age and National Institutes of Health Stroke Scale‐100 Index; and THRIVE, Totaled Health Risks in Vascular Events.