How do aspirin (acetylsalicylic acid) and Plavix (clopidogrel) help acutely in the management of an ischemic stroke?

From the Guidelines

Aspirin and Plavix (clopidogrel) help acutely for ischemic strokes by preventing further blood clot formation and growth, with aspirin typically given as a 325mg loading dose within 24-48 hours of symptom onset, followed by 81mg daily for long-term prevention, and Plavix usually administered as a 300-600mg loading dose followed by 75mg daily, often in combination with aspirin for the first 21 days after a stroke or TIA, as supported by the most recent and highest quality study 1.

Key Points

• Aspirin and Plavix work through different antiplatelet mechanisms: aspirin irreversibly inhibits cyclooxygenase enzymes, preventing thromboxane A2 production and platelet aggregation, while Plavix blocks the P2Y12 receptor on platelets, preventing their activation 1.
• The dual antiplatelet therapy provides more comprehensive protection against clot formation than either medication alone, but is only beneficial for ischemic strokes (caused by blood clots) and is contraindicated in hemorrhagic strokes as they can worsen bleeding 1.
• Patients should take these medications with food to reduce gastrointestinal side effects and should be monitored for bleeding complications, with the benefits of dual antiplatelet therapy outweighing the risks for most patients, as shown in the POINT trial 1.

Dosage and Administration

• Aspirin: 325mg loading dose within 24-48 hours of symptom onset, followed by 81mg daily for long-term prevention 1.
• Plavix: 300-600mg loading dose followed by 75mg daily, often in combination with aspirin for the first 21 days after a stroke or TIA 1.

Important Considerations

• The most recent and highest quality study 1 supports the use of dual antiplatelet therapy with aspirin and Plavix for the first 21 days after a stroke or TIA, with a significant reduction in the risk of ischemic stroke and a moderate increase in the risk of major hemorrhage.
• The benefits of dual antiplatelet therapy should be weighed against the risks for each individual patient, taking into account their specific clinical characteristics and medical history 1.

From the FDA Drug Label

The CURE study included 12,562 patients with ACS without ST-elevation (UA or NSTEMI) and presenting within 24 hours of onset of the most recent episode of chest pain or symptoms consistent with ischemia Patients were required to have either ECG changes compatible with new ischemia (without ST-elevation) or elevated cardiac enzymes or troponin I or T to at least twice the upper limit of normal. Patients were randomized to receive clopidogrel (300 mg loading dose followed by 75 mg once daily) or placebo, and were treated for up to one year Patients also received aspirin (75 to 325 mg once daily) and other standard therapies such as heparin.

Table 4: Outcome Events in the CURE Primary Analysis

• Other standard therapies were used as appropriate. †The individual components do not represent a breakdown of the primary and coprimary outcomes, but rather the total number of subjects experiencing an event during the course of the study Outcome Clopidogrel (+ aspirin)* (n=6259) Placebo (+ aspirin)* (n=6303) Relative Risk Reduction (%) (95% CI) Primary outcome (Cardiovascular death, MI, stroke) 582 (9.3%) 719 (11.4%) 20% (10.3,27.9) p <0.001 All Individual Outcome Events: † CV death 318 (5.1%) 345 (5.5%) 7% (-7.7,20.6) MI 324 (5.2%) 419 (6.6%) 23% (11,33.4)

Stroke 75 (1.2%) 87 (1.4%) 14% (-17.7,36. 6)

The combination of aspirin and clopidogrel helps acutely for a stroke by reducing the risk of cardiovascular death, myocardial infarction (MI), and stroke.

• The CURE study showed a 20% relative risk reduction in the primary outcome of cardiovascular death, MI, or stroke in patients treated with clopidogrel and aspirin compared to those treated with placebo and aspirin 2.
• The CAPRIE trial also demonstrated the efficacy of clopidogrel in reducing the risk of ischemic stroke, MI, and vascular death in patients with recent myocardial infarction, ischemic stroke, or peripheral arterial disease 2.
• The benefits of aspirin and clopidogrel are thought to be due to their antiplatelet effects, which help prevent the formation of blood clots that can cause strokes and other cardiovascular events.
• Key points:
  • Aspirin and clopidogrel are commonly used together to prevent cardiovascular events.
  • The combination has been shown to be effective in reducing the risk of stroke, MI, and cardiovascular death.
  • The CURE study and CAPRIE trial provide evidence for the efficacy of aspirin and clopidogrel in acute stroke management 2.

From the Research

Aspirin and Plavix for Acute Stroke

• Aspirin and Plavix (clopidogrel) are antiplatelet medications that help prevent blood clots from forming in the brain, which can cause a stroke 3, 4, 5, 6, 7.
• The use of aspirin in acute ischemic stroke has been shown to decrease death or dependency at the end of follow-up, with a number needed to treat for an additional beneficial outcome of 79 3.
• Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been found to be more effective than aspirin alone in reducing the risk of recurrent stroke, but it also increases the risk of major bleeding events 4, 5, 7.
• The addition of clopidogrel to aspirin for patients with transient ischemic attack (TIA) or minor ischemic stroke appears to significantly reduce the risk of ischemic stroke recurrence, but with a possible increase in the risk of bleeding compared to aspirin alone 5.

Benefits and Risks

• The benefits of aspirin and Plavix in acute stroke include:
  • Reduced risk of death or dependency 3
  • Reduced risk of recurrent ischemic stroke 4, 5
• The risks of aspirin and Plavix in acute stroke include:
  • Increased risk of major bleeding events 4, 5, 7
  • Increased risk of hemorrhagic stroke 4, 5

Treatment Guidelines

• Aspirin should be started as soon as possible after the onset of acute ischemic stroke, at a dose of 160 mg to 300 mg daily 3, 6.
• Dual antiplatelet therapy with aspirin and clopidogrel may be considered for patients with high-risk TIA or minor ischemic stroke, but the duration of treatment should be individualized based on the patient's risk of ischemia and hemorrhage 7.