Should a patient 4 days post-acute lacunar infarct (cerebral infarction) be treated with dual antiplatelet therapy or aspirin (acetylsalicylic acid) alone?

From the Guidelines

For a patient who is 4 days out from an acute lacunar infarct, dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is still recommended rather than aspirin alone. The optimal regimen would be aspirin 81 mg daily plus clopidogrel 75 mg daily for 21 days, then transitioning to a single antiplatelet agent (typically aspirin) for long-term secondary prevention, as recommended by the Canadian Stroke Best Practice Recommendations for acute stroke management 1. This approach is supported by evidence from the CURE trial, which demonstrated a reduction in cardiovascular death, nonfatal MI, or stroke with the addition of clopidogrel to aspirin in patients with acute coronary syndrome 1. Key considerations for DAPT in this context include:

• Initiating therapy as soon as possible after the stroke, ideally within 24 hours of symptom onset, and within 12 hours if possible 1
• Using a minimal loading dose of 300 mg Clopidogrel and 160 mg of ASA at the start of treatment 1
• Continuing DAPT for 21-30 days, followed by antiplatelet monotherapy indefinitely 1
• Assessing for contraindications such as active bleeding, planned surgical procedures, or history of intracranial hemorrhage before initiating DAPT
• Monitoring for potential bleeding risks, particularly in patients with high bleeding risk, and adjusting the treatment regimen as needed.

From the FDA Drug Label

The use of clopidogrel in CURE was associated with a decrease in the use of thrombolytic therapy (71 patients [1. 1%] in the clopidogrel group, 126 patients [2%] in the placebo group; relative risk reduction of 43%), and GPIIb/IIIa inhibitors (369 patients [5.9%] in the clopidogrel group, 454 patients [7. 2%] in the placebo group, relative risk reduction of 18%). The primary outcome (CV death, MI, or stroke) was 582 (9.3%) in the clopidogrel-treated group and 719 (11.4%) in the placebo-treated group, a 20% relative risk reduction (95% CI of 10% to 28%; p <0. 001) for the clopidogrel-treated group

The patient should consider going on dual antiplatelet therapy with clopidogrel and aspirin, as it has been shown to reduce the risk of cardiovascular death, MI, or stroke by 20% compared to aspirin alone 2. This is particularly relevant for patients who are 4 days out from an acute lacunar infarct, as the benefits of clopidogrel were observed independently of the dose of aspirin and were maintained throughout the course of the trial (up to 12 months). Dual antiplatelet therapy may be beneficial in reducing the risk of further cardiovascular events.

From the Research

Dual Antiplatelet Therapy vs Aspirin Alone for Lacunar Infarct

• The decision to use dual antiplatelet therapy (DAPT) or aspirin alone in patients with lacunar infarct depends on various factors, including the risk of recurrent stroke and bleeding complications.
• A study published in The New England Journal of Medicine in 2012 3 found that the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke in patients with recent lacunar strokes, but did increase the risk of bleeding and death.
• In contrast, a study published in Acta Neurologica Scandinavica in 2019 4 found that aspirin significantly reduced the risk of recurrent stroke in patients with lacunar stroke.
• A review article published in the Journal of Stroke and Cerebrovascular Diseases in 2019 5 noted that escalation of antithrombotic treatments beyond standard single antiplatelet agents has not been effective in long-term lacunar stroke prevention efforts, and may increase the risk of intracerebral hemorrhage and systemic bleeding.
• A meta-analysis published in Stroke in 2021 6 found that DAPT therapy with P2Y12 inhibitors and aspirin reduced the risk of stroke recurrence by 24% compared to aspirin alone, but was associated with an increased risk of severe or moderate bleeding.

Considerations for Patients 4 Days Out from Acute Lacunar Infarct

• For patients who are 4 days out from an acute lacunar infarct, the risk of recurrent stroke and bleeding complications should be carefully considered when deciding between DAPT and aspirin alone.
• The study published in The New England Journal of Medicine in 2012 3 suggests that aspirin alone may be sufficient for patients with lacunar infarct, as the addition of clopidogrel did not provide a significant benefit in reducing recurrent stroke risk.
• However, the meta-analysis published in Stroke in 2021 6 suggests that DAPT therapy may be beneficial in reducing stroke recurrence risk, although this must be balanced against the increased risk of bleeding complications.
• The study published in Acta Neurologica Scandinavica in 2019 4 provides evidence that aspirin alone can be effective in reducing recurrent stroke risk in patients with lacunar stroke.
• It is also worth noting that a study published in the Journal of Clinical Medicine in 2024 7 compared the effectiveness of potent P2Y12 inhibitors versus clopidogrel in patients with acute myocardial infarction undergoing PCI, but this study is not directly relevant to the treatment of lacunar infarct.