How to resume a trial in patients with a history of ischemic events?

From the FDA Drug Label

The CAPRIE trial was a 19,185-patient, 304-center, international, randomized, double-blind, parallel-group study comparing clopidogrel (75 mg daily) to aspirin (325 mg daily) To be eligible to enroll, patients had to have: 1) recent history of myocardial infarction (within 35 days); 2) recent histories of ischemic stroke (within 6 months) with at least a week of residual neurological signs; and/or 3) established peripheral arterial disease (PAD). The efficacy of clopidogrel relative to aspirin was heterogeneous across these subgroups (p=0. 043) (see Figure 8). The benefit was most apparent in patients who were enrolled because of peripheral arterial disease and less apparent in stroke patients In patients who were enrolled in the trial on the sole basis of a recent myocardial infarction, clopidogrel was not numerically superior to aspirin.

The decision to resume a trial in patients with a history of ischemic events should be based on the individual patient's condition and medical history.

• Key considerations include the type and severity of the ischemic event, the patient's current treatment regimen, and their overall health status.
• Clopidogrel may be considered for patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease, as it has been shown to reduce the risk of subsequent ischemic events in these patients 1.
• However, the benefit of clopidogrel may vary depending on the individual patient's characteristics, and the decision to resume a trial should be made on a case-by-case basis.
• Aspirin is also effective in reducing cardiovascular events in patients with recent myocardial infarction or stroke, and the choice between clopidogrel and aspirin should be based on the individual patient's needs and medical history.

From the Research

Resuming a clinical trial in patients with a history of ischemic events should be done with caution, prioritizing a thorough cardiovascular assessment and optimal management of cardiovascular risk factors, as evidenced by the most recent study 2.

Key Considerations

• Conduct a thorough cardiovascular assessment including ECG, cardiac biomarkers, and imaging to establish the patient's current status and risk level.
• Implement appropriate antiplatelet therapy, considering the latest evidence suggesting that switching to or adding alternative antiplatelet agents may be beneficial in preventing subsequent vascular events 2.
• Ensure optimal management of cardiovascular risk factors, including:
  • Blood pressure control (target <130/80 mmHg)
  • Lipid management with statins (such as atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily)
  • Diabetes control if applicable (target HbA1c <7%)

Antiplatelet Therapy

• Aspirin 81-325 mg daily may be considered, possibly combined with clopidogrel 75 mg daily for high-risk patients, although the combination of aspirin and clopidogrel may not be significantly more effective in preventing serious vascular events than clopidogrel alone due to cumulative excess of bleeding complications 3.
• The choice of antiplatelet therapy should be individualized based on the patient's risk profile and medical history.

Trial Resumption

• The trial should resume at a reduced dose or modified schedule based on the severity of the previous ischemic event, with a minimum waiting period of 3-6 months after the event.
• Implement more frequent monitoring, including regular cardiovascular assessments every 2-4 weeks initially, to balance the benefits of continued trial participation against the risk of recurrent ischemic events.

Underlying Pathophysiology

• Recognize that the underlying pathophysiology of ischemia (plaque rupture, thrombosis, and vascular inflammation) requires comprehensive management to prevent recurrence during trial participation.
• Consider the latest evidence on antiplatelet therapy and cardiovascular risk management to inform decision-making 4, 5, 6.