Brain Metastases Are Not an Absolute Contraindication for Antiplatelet Therapy

Like Balancing on a Razor’s Edge

Oncology patients are at risk of hypercoagulable states, while intracranial bleeding is a frequent complication of primary brain tumors or brain metastases. The indication for drugs that influence the blood-clotting process must be based on a careful assessment of benefits and risks. Several studies have confirmed that systemic exposure to anticoagulants does not significantly increase the risk of intracranial bleeding in patients with malignant CNS lesions, thus the treatment of venous thromboembolic complications in these patients relies on anticoagulants, just like in others.

Many cancer patients need to take antiplatelet agents (antithrombotic drugs), such as acetylsalicylic acid (ASA) and P2Y₁₂ receptor antagonists (e.g., clopidogrel or ticagrelor), due to comorbidities. It is well documented that in the general population, antiplatelet agents slightly increase the risk of gastrointestinal bleeding, but there has been no conclusive evidence concerning CNS bleeding. Therefore, until recently, the safety of these agents in patients with brain metastases was unknown.

Cohort Study

An interesting study from prestigious Boston institutions (Harvard Medical School, Beth Israel Deaconess Medical Center, and Dana-Farber Cancer Institute) provided new insights. Researchers conducted a retrospective study analyzing data from 392 patients with brain metastases. Out of these, 134 started using antiplatelet drugs within one month before their cancer diagnosis or at any time thereafter. Each of these patients was matched with a comparable control without antiplatelet therapy.

In the studied cohort, lung cancers were the most common diagnosis − 74.0% of patients had non-small cell lung cancer (NSCLC) and 9.9% had small cell lung cancer (SCLC). Patients on antiplatelet therapy most frequently used ASA monotherapy (86.6%), dual antiplatelet therapy with ASA and clopidogrel was used by 9.0%, and 23.1% received both antiplatelet agents and anticoagulants (mainly enoxaparin, less frequently DOACs).

Study Findings

The study revealed the following insights:

• The incidence of intracranial bleeding after 1 year did not differ significantly between the groups: 22.5% (95% confidence interval [CI] 15.2–29.8) in patients on antiplatelet agents and 19.3% (95% CI 14.1–24.4) in the control group (p = 0.22).
• Using antiplatelet drugs was not associated with the extent or severity of intracranial bleeding.
• Major bleeding occurred in about 5.5% of cases in both groups.
• Combining antiplatelet agents with anticoagulants did not significantly increase the risk of major intracranial bleeding compared to patients only on antiplatelet therapy (hazard ratio [HR] 0.40; 95% CI 0.05–3.25; p = 0.39).
• There was a slight increase in overall survival in patients taking antiplatelet drugs (median 9.4 vs. 8.2 months; p = 0.03).

In the subgroup of patients with NSCLC, the results were very similar; for instance, the incidence of intracranial bleeding after 1 year was 17.0% in patients on antiplatelet agents and 18.6% in the control group (p = 0.95).

Conclusion

Antiplatelet therapy should not be overly feared in patients with brain metastases. Findings from the retrospective study by Boston authors support the use of antiplatelet agents in these patients when indicated. Although combining antiplatelet agents with anticoagulants appeared safe in the studied cohort, this assumption needs confirmation through further clinical research.

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Sources:
1. Miller E. J., Patell R., Uhlmann E. J. et al. Antiplatelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors. Blood Adv 2022; 6 (5): 1559−1565, doi: 10.1182/bloodadvances.2021006470.
2. Quant Lee E., Wen P. Y. Treatment and prevention of venous thromboembolism in patients with brain tumors. UpToDate, 2022 May 17. Available at: www.uptodate.com/contents/treatment-and-prevention-of-venous-thromboembolism-in-patients-with-brain-tumors