Investigational drugs for ischemic stroke: what’s in the clinical development pipeline for acute phase and prevention?

ABSTRACT

Introduction

Stroke is a leading cause of disability and mortality and its burden expected to increase. The only approved drug for acute ischemic stroke (IS) is the intravenous thrombolytic alteplase. The risk of bleeding complications is one of the reasons for the undertreatment of eligible patients. Numerous drugs are currently being developed to improve safety-efficacy.

Areas covered

We reviewed literature from 1 January 2000, to 15 January 2022 for the development and testing of novel drugs with the aim of targeting treatment at prevention of ischemic stroke: PubMed, MEDLINE, Google Scholar, and ClinicalTrial.gov.

Expert opinion

The pathophysiology of IS involves multiple pathways causing cerebral artery obstruction and brain tissue ischemia. Data suggest that tenecteplase is a promising fibrinolytic agent with a superior efficacy-safety profile, compared to alteplase. Current guidelines consider a short-term cycle of mannitol or hypertonic saline to be advisable in patients with space-occupying hemispheric infarction. Regarding primary and secondary prevention, research is primarily focused on identifying mechanisms to improve the safety-efficacy profile using a ‘hemostasis-sparing’ approach. Further evaluation on those agents that have shown promise for their risk/benefit profiles, would benefit greatly a neurologist’s capacity to successfully prevent and treat IS patients.

KEYWORDS:

• Acute ischemic stroke therapy
• anticoagulants
• anti-FXIa
• antiplatelets
• endovascular treatment
• fibrinolytic
• intravenous thrombolysis
• ischemic stroke
• ischemic brain/cerebral edema/swelling

Article highlights

• Ischemic stroke is a leading cause of disability and death worldwide and is expected to increase health-care burden due to both population growth and aging.

• The only approved drug for acute ischemic stroke is the intravenous thrombolytic alteplase. The risk of potential bleeding complications, especially symptomatic intracerebral hemorrhage, is one of the causes of the undertreatment of eligible patients.

• Tenecteplase is a new-generation thrombolytic drug, with a better efficacy and safety profile than alteplase.

• Short-term administration of mannitol or hypertonic saline is considered advisable in patients with space-occupying hemispheric infarction.

• Anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation promote selective inhibition of single factors active in the intrinsic pathways of the coagulation cascade, thus preserving the extrinsic-common pathways intact for hemostasis. Novel molecules are under investigation for their improved efficacy-safety profiles.

• The safety-efficacy profiles from research based on pharmaco-genetics are under investigation.

Acknowledgments

This work has been supported by the Italian Ministry of Heatlh Ricerca Corrente – IRCCS MultiMedica.

Declaration of interest

The authors have no 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.