Does aspirin provide protection against recurrent pulmonary embolism (PE)?

Aspirin for Prevention of Recurrent Pulmonary Embolism

Aspirin provides modest protection against recurrent PE (approximately 30-35% risk reduction compared to placebo), but anticoagulation is substantially superior and should be used instead whenever possible. 1

Primary Recommendation: Anticoagulation Over Aspirin

For patients completing initial treatment who will receive extended secondary prevention, use anticoagulation (preferably reduced-dose DOACs) rather than aspirin. 1

Evidence Supporting Anticoagulation Superiority

• Compared to aspirin, anticoagulation prevents 39 additional recurrent VTE events per 1,000 patients over 2-4 years, with only 4 additional major bleeding events per 1,000 patients 1
• Aspirin increases the risk of recurrent PE 3-fold (RR 3.10; 95% CI 1.24-7.73) and DVT 3-fold (RR 3.15; 95% CI 1.50-6.63) compared to continued anticoagulation 1
• The 2021 CHEST guidelines provide a strong recommendation for reduced-dose DOACs over aspirin for extended therapy 1
• The 2020 ASH guidelines conditionally recommend anticoagulation over aspirin based on moderate-certainty evidence 1

When Aspirin May Be Considered

Aspirin should only be used when patients refuse or cannot tolerate anticoagulation after completing initial treatment. 1, 2

Specific Clinical Scenario

For patients with unprovoked proximal DVT or PE who are stopping anticoagulant therapy and have no contraindication to aspirin:

• Use aspirin 75-100 mg daily over no treatment 1, 2
• This represents a weak recommendation based on low-certainty evidence 1
• Aspirin reduces recurrent VTE by approximately 53 events per 1,000 patients over 2-4 years compared to placebo 1
• Major bleeding risk increases by only 3 events per 1,000 patients 1

Critical Caveat

Aspirin is NOT an acceptable alternative to anticoagulation for patients who want extended therapy. 1, 2 The net benefit of extended anticoagulation is substantially greater than aspirin, and some anticoagulants carry similar bleeding risk to aspirin 1

Practical Algorithm for Decision-Making

Step 1: Assess Candidacy for Extended Anticoagulation

• If patient can tolerate anticoagulation: Use reduced-dose DOAC (apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily) 1
• If patient refuses or has contraindication to anticoagulation: Proceed to Step 2 1

Step 2: For Patients Stopping Anticoagulation

• If no contraindication to aspirin: Use aspirin 75-100 mg daily 1, 2
• If contraindication to aspirin: No additional thromboprophylaxis 1

Step 3: Reassess Periodically

• Reevaluate whether anticoagulation has become acceptable or feasible 1
• Consider that aspirin may have been stopped when anticoagulants were started and should be reconsidered when stopping anticoagulation 1

Common Pitfalls to Avoid

Do not use aspirin for acute PE treatment. Aspirin has no role in primary management of acute PE; therapeutic anticoagulation for at least 3 months is mandatory 2

Do not continue aspirin when starting anticoagulation. For patients already taking aspirin for cardiovascular disease who develop PE, suspend aspirin during anticoagulation therapy to avoid increased bleeding risk (RR 1.26 for major bleeding) 2, 3

Do not substitute aspirin for anticoagulation in unprovoked PE. This leads to treatment failure with significantly higher recurrent VTE rates 1, 2

Magnitude of Benefit

While aspirin does provide some protection:

• 32% reduction in recurrent VTE compared to placebo 4, 5
• 34% reduction in major vascular events 5
• Low bleeding risk profile 5

However, this benefit is substantially inferior to anticoagulation, which provides approximately 79% reduction in recurrent VTE compared to placebo 4