Intravenous thrombolysis in acute ischemic stroke: standard and potential future applications

Abstract

Acute ischemic stroke is a medical emergency requiring urgent treatment. Randomized clinical trial and Phase IV data have provided unequivocal evidence that intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) improves early functional outcomes by restoring brain perfusion. Moreover, these studies have shed substantial light on the factors which are associated with more favorable outcome with tPA and are related to the highest benefit-to-risk ratio. Stroke physicians should consider vascular imaging techniques to aid decision making with thrombolytic therapy. The presence of intracranial occlusion is the target of treatment with early recanalization being the goal. Successful use of intravenous thrombolysis depends on a sound understanding of the decision-making process and organization of the treating team who strives for early treatment initiation and strict adherence to the protocol. Intravenous rt-PA within 4.5 h of onset should now be a standard treatment of acute disabling ischemic stroke throughout the world. This review also summarizes intravenous thrombolysis contraindications as well as the safety of novel reperfusion therapies including tenecteplase, sonothrombolysis and the combination of alteplase with direct thrombin inhibitors or glycoprotein IIb/IIIa receptor antagonists.

Keywords::

• acute ischemic stroke
• outcomes
• systemic thrombolysis
• recanalization
• tPA

Financial & competing interests disclosure

G Tsivgoulis and M Haršány have been supported by European Regional Development Fund – Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123). M Haršány has been supported by European Social Fund and the State Budget of the Czech Republic – Project Young Talent Incubator II (Reg. No. CZ.1.07/2.3.00/20.0117). AV Alexandrov served as a consultant for Genentech, and serves as Chairman of the Scientific Advisory Board for Cerevast Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Intravenous (iv.) thrombolysis remains the only proven medical treatment for improving neurological deficit and functional outcome in the setting of acute ischemic stroke (AIS).

• The efficacy of iv. thrombolysis is independent of age and baseline stroke severity.

• Onset-to-treatment time is the most important effect modifier of the favorable outcome of AIS patients treated with iv. thrombolysis.

• The time window of opportunity for treatment with iv. tissue plasminogen activator is still limited to the first 4.5 h of ictus and consequently the majority of AIS patients are precluded from this therapy.

• Complete recanalization occurs in the minority of patients treated with systemic thrombolysis and location of occluded vessel is the most important determinant of successful brain reperfusion.

• Ongoing clinical trials aim to improve rates of recanalization, widen the treatment window or broaden eligibility so that more AIS patients can benefit from reperfusion therapies.

• It remains absolutely crucial that patients are transferred to comprehensive stroke centers in order to be treated rapidly with iv. thrombolysis (mandatory door-to-needle time <60 min, optimal door-to-needle time <30 min).