(CVP003) IMPACT OF ANTICOAGULANTS FOR ARTERIAL THROMBOEMBOLISM PREVENTION AMONG AMBULATORY CANCER PATIENTS BY PRIMARY TUMOUR SITE: SYSTEMATIC REVIEW AND META-ANALYSIS

Background: The incidence of arterial thromboembolism (ATE) following a new diagnosis of cancer varies by primary tumour site. However, it is unclear whether this alters the benefit-to-harm profile of anticoagulation for primary ATE prevention among patients with cancer. Therefore, we sought to systematically evaluate the efficacy and safety of anticoagulants for primary ATE prevention among ambulatory cancer patients with a focus on tumour sites.

METHODS AND RESULTS: We conducted a systematic review and meta-analysis using Medline, Embase, SCOPUS, and CENTRAL from inception to November 28, 2022. We included randomized trials comparing prophylactic oral or parenteral anticoagulation to no anticoagulant use, among ambulatory patients with solid tumours or lymphoma who initiated tumor-directed systemic therapy. Eligible studies reported symptomatic ATEs, defined as ischemic stroke, acute myocardial infarction or peripheral artery occlusion, either as an efficacy outcome or adverse event. The incidence of ATE and major bleeding, as well as risk differences attributable to anticoagulation were meta-analyzed by primary tumour site and the Khorana risk score using a random-effects model. We contacted study authors for unpublished data or individual patient data if potentially eligible publications did not provide tumour site-specific ATE data. Risk of bias assessment was completed using the Cochrane Risk of Bias 2 tool. This study was registered under PROSPERO (CRD42022315125).

From 7,695 records identified, 9 randomized controlled trials involving 8,709 patients were included. Follow-up duration ranged from 3.3 to 68 months (median 6.6 months). Prophylactic anticoagulation was associated with a reduced risk of ATE among patients with pancreatic cancer (risk difference [RD] -3.2%; 95% confidence interval [CI] -5.7% to -0.8%; p=0.01) compared to no anticoagulation, without a detectable increase in the risk of major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; p=0.31, Table). However, there was no statistically significant reduction in ATE risk with prophylactic anticoagulation for other tumour sites. The magnitude of absolute ATE risk reduction was higher with anticoagulant use among patients with Khorana risk score ≥2 (RD -1.1%, 95% CI -2.6% to 0.4%), compared to those with Khorana risk scores 0-1 (RD -0.2%; 95% CI -1.1% to 0.6%; p = 0.35 for subgroup difference, Figure).

Conclusion: Based on limited certainty of evidence, prophylactic anticoagulation among ambulatory patients with pancreatic cancer reduced the risk of ATE. In addition to its efficacy in the prevention of venous thromboembolism, prophylactic anticoagulation should be considered to reduce ATE events in patients with pancreatic cancer.

Lay Abstract Content: Arterial thromboembolism, or clot involving the arteries (such as heart attacks, strokes or artery diseases involving the legs) poses a serious threat to one's life by blocking blood flow to vital organs such as the heart or the brain. Patients with cancer are susceptible to arterial clots due to cancer-related factors such as inflammation, chemotherapy, and radiation therapy. For patients living with cancer who are at a high risk of developing clots in the veins, doctors may prescribe anticoagulants or blood-thinners. This medication helps prevent blood clots from forming by slowing down the clotting process in the blood and reducing the risk of blood clots in the veins. However, studies on the impact of blood-thinners on clot prevention in the arteries are rare. In our study, we aimed to determine whether blood-thinners could be used to prevent arterial clots in patients with different types of cancer.

To determine the effectiveness and safety of blood-thinners in preventing arterial clots in cancer patients according to the site of the tumor, we conducted a comprehensive review of previous studies. We found that blood-thinners can effectively reduce the risk of arterial clots in patients with pancreatic cancer without increasing the risk of major bleeding. However, we did not find evidence to support the use of blood-thinners to prevent arterial clots in patients with other types of cancer.

Our study also examined the relationship between blood-thinner use and a patient's Khorana risk score. The Khorana risk score is a tool used by physicians to predict the likelihood of developing vein clots in cancer patients. It considers factors like the type of cancer and the patient's blood cell count. We found that patients with a higher Khorana risk score had lower risk of developing artery clots while on blood-thinners as well.

In conclusion, our study suggests that blood-thinners may be a safe and effective way to prevent artery clots in patients with pancreatic cancer. In addition to blood-thinners’ proven effectiveness at preventing vein clots, doctors should consider using them in pancreatic cancer patients to prevent artery clots as well.