Is there an indication to take clopidogrel and Aggrenox (dipyridamole and aspirin) together?

From the Guidelines

Taking clopidogrel and Aggrenox together is generally not recommended due to the increased risk of bleeding without proven additional benefit. The most recent and highest quality study, published in 2021 1, indicates that the continuous use of dual antiplatelet therapy (aspirin plus clopidogrel) for more than 90 days or the use of triple antiplatelet therapy is associated with an excess risk of hemorrhage. Aggrenox already contains two antiplatelet medications (aspirin and dipyridamole), and adding clopidogrel would create triple antiplatelet therapy, significantly increasing bleeding risk while clinical evidence doesn't support improved outcomes for most patients. Some key points to consider include:

• The selection of an antiplatelet agent should be individualized on the basis of patient risk factor profiles, cost, tolerance, and other clinical characteristics 1.
• The addition of aspirin to clopidogrel increases the risk of hemorrhage and is not recommended for routine secondary prevention after ischemic stroke or TIA 1.
• In very specific circumstances, such as certain high-risk cardiovascular patients who have failed other therapies or immediately after specific procedures like complex coronary stenting, a cardiologist might temporarily prescribe this combination with careful monitoring.
• If you're currently taking both medications, consult your healthcare provider before making any changes. The underlying concern is that all these medications work to prevent blood clotting through different mechanisms - clopidogrel blocks the P2Y12 receptor on platelets, aspirin inhibits thromboxane production, and dipyridamole increases cyclic AMP levels - creating a potentially dangerous cumulative antiplatelet effect. It's essential to weigh the potential benefits against the risks and consider alternative treatment options that can provide adequate protection without significantly increasing the risk of bleeding. In general, the use of antiplatelet agents should be guided by the most recent clinical guidelines and individualized to each patient's specific needs and risk factors, as recommended by studies such as the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

From the Research

Combination Therapy with Clopidogrel and Aggrenox (Dipyridamole and Aspirin)

• The use of clopidogrel and Aggrenox (dipyridamole and aspirin) together is not universally recommended due to the increased risk of bleeding 2, 3.
• Studies have shown that combination therapy with aspirin plus clopidogrel is not recommended for patients with ischemic stroke or TIA due to the increased risk of hemorrhage 2.
• The CHARISMA trial demonstrated a lack of significant clinical efficacy and an increased risk of bleeding with clopidogrel plus aspirin compared with aspirin alone 2, 3.
• However, some studies suggest that clopidogrel plus aspirin may be more effective than aspirin alone in reducing the risk for recurrent stroke, but with an increased risk of major bleeding events 4.

Specific Patient Populations

• The combination of clopidogrel and aspirin may be considered in patients with non-ST-segment elevation acute coronary syndrome or undergoing percutaneous coronary intervention 5.
• The combination of aspirin and clopidogrel should be reserved for special populations requiring this antiplatelet combination, such as those who have had coronary artery stenting 3.
• Patients with a history of ischemic stroke or TIA may be treated with aspirin, clopidogrel, or extended-release dipyridamole plus aspirin as acceptable first-line options for secondary prevention of ischemic events 3, 6.

Safety and Efficacy

• The safety and efficacy of clopidogrel and/or aspirin for ischemic stroke/transient ischemic attack have been evaluated in several systematic reviews and meta-analyses, with results showing that clopidogrel plus aspirin is more effective than aspirin alone in reducing the risk for recurrent stroke, but with an increased risk of major bleeding events 4.
• The risk of bias and methodological validity of the included studies ranged from low to high, according to ROBIS and AMSTAR 2 parameters 4.