Low-Dose vs Standard-Dose tPA for Neurologic Recovery in Acute Ischemic Stroke

MRA of a stroke victim's brain
MRA of a stroke victim’s brain
Administration of intravenous tPA is associated with significant improvement in neurologic function following acute ischemic stroke; however, this treatment is associated with increased cost as well as risk for intracranial hemorrhage.

Patients with acute ischemic stroke (AIS) experience similar neurologic improvement with low-dose and standard-dose tissue plasminogen activator (tPA), but low-dose tPA may be preferred for its ability to reduce the risk for symptomatic intracranial hemorrhage (SICH), according to findings from a systematic review and meta-analysis published in the Journal of Stroke and Cerebrovascular Diseases.

Researchers reviewed 12 high-quality clinical trials consisting of patients receiving either low-dose tPA (n=2888) or standard-dose tPA (n=4798). The investigators chose 0.75 mg/kg as the low-dose determination for this analysis, using the average of 0.9 mg/kg for standard dose and 0.6 mg/kg for low-dose. The primary efficacy outcome was determined by the modified Rankin scale (mRs) score.

Low-dose tPA and standard-dose tPA were associated with similar improvements in outcome (odds ratio [OR] = .92, 95% CI: 0.84-1.02; P =.12) and functional independence (OR = .97, 95% CI: 0.88-1.08; P =.57). Low-dose tPA was associated with a significantly greater reduction in SICH than standard-dose tPA based on the National Institute of Neurological Disorders and Stroke (OR = .71, 95% CI: 0.57-0.89; P =.003) and Safe Implementation of Thrombolysis in Stroke Monitoring Study (OR = .64, 95% CI: 0.42-0.99; P =.04) definitions. Both tPA doses were associated with similar reductions in mortality (OR = .87, 95% CI: 0.74-1.02; P =.08).

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Definitions for low-dose tPA were inconsistent among the trials included in the review and meta-analysis. In addition, the majority of the trials included patients of Asian descent, limiting the generalizability of the findings.

The investigators conclude that lowering the tPA dose as well as the burden of intravenous thrombolytic therapy “will greatly promote the implementation of this therapy and improve the neurologic recovery in patients with AIS.”


Cheng JW, Zhang XJ, Cheng LS, et al. Low-dose tissue plasminogen activator in acute ischemic stroke: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2018;27(2):381-390.