Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke

Abstract

In 1995, the NINDS (National Institute of Neurological Disorders and Stroke) tPA (tissue plasminogen activator) Stroke Study Group published the results of a large multicenter clinical trial demonstrating efficacy of intravenous tPA by revealing a 30% relative risk reduction (absolute risk reduction 11%-15%) compared with placebo at 90 days in the likelihood of having minimal or no disability. Since approval in 1996, tPA remains the only drug treatment for acute ischemic stroke approved by the US Food and Drug Administration. Over the years, an abundance of research and clinical data has supported the safe and efficacious use of intravenous tPA in all eligible patients. Despite such supporting data, it remains substantially underutilized. Challenges to the utilization of tPA include narrow eligibility and treatment windows, risk of symptomatic intracerebral hemorrhage, perceived lack of efficacy in certain high-risk subgroups, and a limited pool of neurological and stroke expertise in the community. With recent US census data suggesting annual stroke incidence will more than double by 2050, better education and consensus among both the medical and lay public are necessary to optimize the use of tPA for all eligible stroke patients. Ongoing and future research should continue to improve upon the efficacy of tPA through more rapid stroke diagnosis and treatment, refinement of advanced neuroimaging and stroke biomarkers, and successful demonstration of alternative means of reperfusion.

Keywords: IV tPA; cerebrovascular accident; cerebrovascular disease; rt-PA; rtPA; t-PA.

Figure 1

(A) Death or dependency defined as mRS 2–6. (B) Risk of symptomatic intracerebral hemorrhage. Notes: A and B demonstrate point estimates for ORs and 95% CIs between the tPA and control groups for each of the trials. *References for the listed trials: NINDS, ECASS, ECASS II, ATLANTIS-A,, ATLANTIS-B, and ECASS III. Abbreviations: ATLANTIS, Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke; CI, confidence interval; ECASS, European Cooperative Acute Stroke Study; mRS, modified Rankin Scale; NINDS, National Institute of Neurological Disorders and Stroke; OR, odds ratio; rt-PA, recombinant tissue plasminogen activator; tPA, tissue plasminogen activator.