What is the interaction between Aspirin (Acetylsalicylic Acid) and Plavix (Clopidogrel)?

From the Guidelines

The interaction between Aspirin (Acetylsalicylic Acid) and Plavix (Clopidogrel) is that they are often used together as dual antiplatelet therapy to reduce major cardiovascular events in patients with established ischemic heart disease, but this combination also increases the risk of bleeding, particularly gastrointestinal bleeding 1.

Key Points

• The combination of clopidogrel and aspirin reduces major CV events in patients with established ischemic heart disease, but is not routinely recommended for patients with prior ischemic stroke due to the risk of bleeding 1.
• The risk of GI bleeding increases with the combination of clopidogrel and aspirin, and is further increased by the use of proton pump inhibitors (PPIs) such as omeprazole 1.
• However, the use of PPIs can also reduce the risk of upper GI bleeding in patients taking antiplatelet therapy, particularly in those with a history of upper GI bleeding or multiple risk factors for GI bleeding 1.
• The FDA has advised healthcare providers to reevaluate the need for starting or continuing treatment with a PPI in patients taking clopidogrel, due to the potential for reduced antiplatelet activity 1.

Clinical Considerations

• Patients with prior GI bleeding are at highest risk for recurrent bleeding on antiplatelet therapy, and should be carefully monitored 1.
• The use of aspirin and clopidogrel together should be individualized, taking into account the patient's risk of cardiovascular events and bleeding 1.
• Alternative antiplatelet therapies, such as prasugrel, may be considered in patients who are at high risk of bleeding or have a history of GI bleeding 1.

From the FDA Drug Label

P2Y12 inhibitors (thienopyridines), including clopidogrel, increase the risk of bleeding. ... Risk factors for bleeding include concomitant use of other drugs that increase the risk of bleeding (e.g., anticoagulants, antiplatelet agents, and chronic use of NSAIDs) In CURE, clopidogrel use with aspirin was associated with an increase in major bleeding (primarily gastrointestinal and at puncture sites) compared to placebo with aspirin The incidence of intracranial hemorrhage (0.1%) and fatal bleeding (0. 2%) were the same in both groups. Other bleeding events that were reported more frequently in the clopidogrel group were epistaxis, hematuria, and bruise.

The interaction between Aspirin (Acetylsalicylic Acid) and Plavix (Clopidogrel) is an increased risk of bleeding.

• Concomitant use of Aspirin and Clopidogrel may increase the risk of major bleeding, including gastrointestinal and intracranial hemorrhage.
• The risk of bleeding is a significant concern when using these two medications together, and patients should be closely monitored for signs of bleeding.
• The combination of Aspirin and Clopidogrel may be used in certain clinical situations, but the benefits and risks should be carefully weighed, and the patient's bleeding risk should be carefully assessed 2.

From the Research

Interaction between Aspirin and Plavix

The interaction between Aspirin (Acetylsalicylic Acid) and Plavix (Clopidogrel) is a complex one, with both drugs affecting platelet activation and aggregation in different ways.

• Aspirin irreversibly inhibits cyclooxygenase, preventing the production of thromboxane A(2), a prothrombotic and vasoconstrictive substance 3.
• Clopidogrel, on the other hand, irreversibly prevents platelet activation by blocking the P2Y(12) receptor on the platelet surface, interfering with platelet activation, degranulation, and aggregation 3.

Clinical Implications

The combination of Aspirin and Clopidogrel has been shown to have a stronger antiplatelet effect than either drug alone, translating into superior antithrombotic protection in coronary, cerebral, or peripheral arterial disease 3.

• However, this combination also increases the risk of bleeding complications, as seen in studies such as the MATCH trial, where the addition of Aspirin to Clopidogrel resulted in a higher risk of life-threatening or major bleeding 4.
• Other studies, such as the meta-analysis by 5, have found that the addition of Clopidogrel to Aspirin reduces the risk of ischemic stroke recurrence, but increases the risk of bleeding episodes.

Platelet Reactivity

The dynamics of platelet reactivity over time have been studied in relation to the use of Aspirin and Clopidogrel, with findings suggesting that dual antiplatelet therapy may be more effective in reducing platelet reactivity in minor strokes 6.

• However, the incidence of Clopidogrel non-responsiveness has been reported to be high, with diabetes mellitus identified as an independent predictor of high on-Clopidogrel platelet reactivity 6.
• The study by 7 found that high on-treatment platelet reactivity to Clopidogrel was more frequent than to Aspirin, suggesting that Aspirin may be a better option in certain patient groups.

Key Findings

• The combination of Aspirin and Clopidogrel has a stronger antiplatelet effect than either drug alone 3.
• The addition of Aspirin to Clopidogrel increases the risk of bleeding complications 4.
• Dual antiplatelet therapy may be more effective in reducing platelet reactivity in minor strokes 6.
• High on-treatment platelet reactivity to Clopidogrel is more frequent than to Aspirin 7.