What are the gaps in research for early antithrombotic (anti-clotting) treatment for patients with ischemic (lack of blood flow) stroke?

From the Guidelines

The most significant gaps in research for early antithrombotic treatment for patients with ischemic stroke include the optimal combination of medications, timing of initiation, and duration of dual antiplatelet therapy (DAPT), as well as the effectiveness and potential harm of DAPT among specific subgroups of patients. The current evidence, as outlined in the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack by the American Heart Association/American Stroke Association 1, highlights several areas where further research is needed. Some of the key areas of uncertainty include:

• Optimal combination of medications, timing of initiation, and duration of DAPT, with most trials using aspirin and clopidogrel in combination for 21 to 90 days, but the ideal duration and combination remaining unclear 1
• Effectiveness and potential harm of DAPT among specific subgroups of patients, such as those with large stroke or microhemorrhages, who may be at increased risk of hemorrhagic transformation or other bleeding complications 1
• Effectiveness and selection of a given antiplatelet agent over another in specific subgroups of patients with noncardioembolic stroke, with relatively few head-to-head comparisons of antiplatelet medications having been evaluated for the prevention of recurrent stroke 1
• Benefit of switching antiplatelet agent for patients already taking one antiplatelet medication at the time of stroke, with relatively little evidence from randomized controlled trials to support this practice 1
• Effectiveness of direct oral anticoagulants (DOACs) compared with or in combination with antiplatelet therapy for secondary stroke prevention among patients with noncardioembolic ischemic stroke, which remains an unanswered question 1. Overall, these gaps in research highlight the need for further studies to inform the optimal use of antithrombotic therapy in patients with ischemic stroke.

From the FDA Drug Label

The primary endpoint was based on the time to first event (one per subject). Component counts are for subjects with any event, not necessarily the first The results for the primary efficacy endpoint were generally consistent across most major subgroups including weight, CHADS2 score, prior warfarin use, level of renal impairment, geographic region, and aspirin use at randomization

The gaps in research for early antithrombotic treatment for patients with ischemic stroke are not directly addressed in the provided drug label. Key areas of uncertainty include:

• Optimal timing of antithrombotic treatment initiation
• Specific patient populations that may benefit from early antithrombotic treatment
• Comparison of different antithrombotic agents in the context of early treatment for ischemic stroke
• Long-term outcomes of early antithrombotic treatment in patients with ischemic stroke 2

From the Research

Gaps in Research for Early Antithrombotic Treatment

The current research on early antithrombotic treatment for patients with ischemic stroke has several gaps, including:

• The optimal timing for initiating antithrombotic therapy after thrombolytic treatment, with some studies suggesting that early initiation may be beneficial 3
• The efficacy and safety of combination antithrombotic therapy, including the use of dual antiplatelet therapy and anticoagulant agents 4, 5
• The role of antithrombotic therapy in specific patient populations, such as those with essential thrombocythemia or cerebral venous sinus thrombosis 6, 4
• The transition from acute to secondary prevention of stroke, and the optimal antithrombotic regimen for long-term prevention 7, 5
• The impact of newer anticoagulant agents, such as direct oral anticoagulants (DOACs), on the prevention of stroke 5

Areas of Uncertainty

There are several areas of uncertainty in the research on early antithrombotic treatment for ischemic stroke, including:

• The balance between the benefits and risks of antithrombotic therapy, particularly in patients with a high risk of bleeding 6, 5
• The optimal duration of antithrombotic therapy, and the need for individualized treatment approaches 5
• The role of antithrombotic therapy in patients with specific comorbid conditions, such as atrial fibrillation or mechanical heart valves 5
• The need for further research on the use of antithrombotic agents in combination with other therapies, such as thrombolytic agents or mechanical thrombolysis 4