Front-loading with clopidogrel plus aspirin followed by dual antiplatelet therapy in the prevention of early stroke recurrence

Abstract

Dual antiplatelet therapy with aspirin plus clopidogrel is not recommended for secondary stroke prevention because of lack of effectiveness and increased hemorrhagic risk. Recent studies show that in patients with a very recent transient ischemic attack or minor ischemic stroke loading with 300 mg clopidogrel plus aspirin, followed by clopidogrel 75 mg plus aspirin once daily for up to 90 days significantly decreases the rate of recurrent stroke, especially strokes that occur within few days from the event that led to medical attention, without an increase in severe bleedings. This article reviews the pharmacokinetics and pharmacodynamics of clopidogrel, focusing on loading doses, and summarizes the results of the studies that have shown the effectiveness of the front-loading approach in the early secondary prevention of stroke.

Keywords::

• clopidogrel
• dual antiplatelet therapy
• front-loading
• secondary prevention
• stroke

Financial & competing interests disclosure

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.

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

Key issues

• Long-term dual therapy with clopidogrel 75 mg plus aspirin is not recommended for secondary stroke prevention because of lack of efficacy over clopidogrel monotherapy and increased bleeding risk.

• The risk of stroke recurrence is very high during the first days after a transient ischemic attack or a minor stroke.

• Front-loading with clopidogrel 300 mg plus aspirin, followed by clopidogrel 75 mg plus aspirin once daily, for up to 3 months, significantly decreases recurrent stroke when given very early after the first ischemic event.

• The benefit seems to be mostly due to a reduction of the strokes that occur within a few days after the qualifying event.

• Ongoing trials are testing higher loading doses of clopidogrel and the combination of aspirin, clopidogrel and dypiridamole very early after a transient ischemic attack or a minor ischemic stroke.