Is the bleeding risk lower with Aspirin (acetylsalicylic acid) or Plavix (clopidogrel) when compared to Pradaxa (dabigatran)?

From the Guidelines

When considering bleeding risk with anticoagulant combinations, Pradaxa (dabigatran) plus Plavix (clopidogrel) generally has a lower bleeding risk compared to Pradaxa plus aspirin. This is because Plavix has a more targeted antiplatelet mechanism that inhibits ADP receptors on platelets, while aspirin broadly inhibits both COX-1 and COX-2 enzymes, affecting multiple pathways including those protecting the gastric mucosa 1. However, any combination of an anticoagulant like Pradaxa with either antiplatelet medication significantly increases bleeding risk compared to Pradaxa alone.

Key Considerations

• The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial compared dabigatran with warfarin and found that dabigatran 110 mg twice daily had a lower major bleeding risk (2.71% per year) compared to warfarin (3.36% per year) 1.
• The trial also found that the rate of gastrointestinal bleeding was higher with dabigatran 150 mg twice daily (1.51% per year) than with warfarin (1.02% per year) or dabigatran 110 mg twice daily (1.12% per year) 1.
• The decision to use any anticoagulant-antiplatelet combination should always be based on individualized assessment of both thrombotic and bleeding risks, taking into account factors such as patient age, comorbidities, and concomitant medications.

Recommendations

• If combination therapy with Pradaxa and an antiplatelet medication is necessary, Plavix may be preferred over aspirin due to its more targeted mechanism and potentially lower bleeding risk.
• The duration of combination therapy should be minimized to the shortest time clinically indicated, typically 1-6 months depending on the specific indication.
• Patients on these combinations should be closely monitored for bleeding signs, particularly gastrointestinal bleeding, and should be prescribed proton pump inhibitors for gastric protection.

From the Research

Bleeding Risk Comparison

• The bleeding risk associated with aspirin, Plavix, and Pradaxa (dabigatran) is a critical consideration in antithrombotic therapy.
• A study published in 2018 2 found that triple antithrombotic therapy involving acetylsalicylic acid, clopidogrel, and warfarin or non-vitamin K antagonist oral anticoagulant (NOAC) is associated with a substantially increased risk of bleeding compared with dual antiplatelet therapy (DAPT).
• Another study from 2011 3 reported that antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit (reduction in myocardial infarction) which is negated by a harm of similar magnitude (increase in major haemorrhage).
• A 2020 study 4 found that concomitant aspirin and anticoagulation is associated with increased risk for major bleeding in surgical patients requiring postoperative intensive care.
• A 2014 review 5 discussed the importance of combination therapy with dual antiplatelet therapy and xabans or dabigatran, but noted that the risk of major bleeding event is increased.

Aspirin vs. Plavix with Pradaxa

• There is no direct comparison of bleeding risk between aspirin and Plavix with Pradaxa in the provided studies.
• However, a study from 2018 2 suggested that NOAC combined with P2Y12 inhibitor alone appears to be safer and as effective as triple therapy with warfarin in patients with acute coronary syndromes.
• Another study from 2014 5 recommended choosing from xabans (apixaban and rivaroxaban) in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants.