Patients with cancer have a high risk of recurrent venous thromboembolism (VTE) and major bleeding, which greatly impact the patient’s management and quality of life.
Recurrent VTE in cancer patients
Patients with cancer have a threefold higher risk of VTE recurrence compared to patients with no history of cancer [1]. In addition, recurrent cancer-associated thrombosis (CAT) has a 12-month cumulative incidence of about 21% compared with approximately 7% in patients without cancer [2]. Recurrence of CAT is higher in the first 6 months after the diagnosis and decreases with time [3].
Risk factors for recurrent CAT have been associated with patient, treatment, and cancer-related factors [4].
Risk of bleeding in cancer patients
Additionally, anticoagulant therapy is challenging in cancer patients because of the higher risk of bleeding. Several factors seem to increase this risk, such as the cancer status, the type of procedure, and cancer treatment [5].
Although, most of these risk factors come from studies not standardized for population, event, and treatment (e.g., observational studies or registries) and might have a partially limited value in defining individual risk assessment [3].
The Caravaggio study and its sub-analysis
A sub-analysis tried to identify the risk factors for recurrent VTE and major bleeding in patients with CAT included in the Caravaggio study and treated with apixaban or dalteparin [3].
Caravaggio was a multinational, randomized, open-label, noninferiority study in which patients with cancer and symptomatic or incidental acute proximal deep vein thrombosis or pulmonary embolism were randomized to receive apixaban or deltaparin [6].
The aim was to assess whether oral apixaban would have been non-inferior to subcutaneous dalteparin to prevent recurrent VTE in patients with cancer [6].
Risk factors for recurrent CAT and major bleeding
The sub-analysis evaluated variables potentially predictive for recurrent VTE or major bleeding in a Cox proportional hazard multivariable analysis with backward variable selection [3].
Table 1 summarizes the independent predictors for recurrent VTE, and major bleeding identified [3].
Table 1: Independent predictors for recurrent venous thromboembolism and major bleeding.
| Recurrent VTE predictors | Major bleeding predictors | |
| Increase in risk ≥1.7 and <2.0 |
|
|
| Increase in risk ≥2.0 |
|
|
| Other risk predictors ≥1.00 |
|
|
| ECOG: Eastern Cooperative Oncology Group; DVT: Deep vein thrombosis; VTE: Venous thromboembolism. Data taken from [3]. | ||
As previously shown, the risk of recurrent VTE and major bleeding seems related to the cancer site and its progression. The analysis showed that the risk of recurrence and major bleeding is higher for patients with gynecological or genitourinary cancer, pancreatic or hepatobiliary cancer, upper gastrointestinal or non-resected luminal gastrointestinal cancer, and metastatic cancer [3].
In addition, the analysis confirmed that cancer treatments could increase the risk of recurrent VTE, as previously known. However, it is impossible to correlate the risk of recurrence with a specific agent or class of agents, being the large spectrum of anticancer agents and their variable administration in each patient [3].
A high creatinine clearance was found to be independently associated with recurrent VTE. Although, it should be pointed out that in the Caravaggio study, the average creatinine clearance was 99.2 ml/min in patients with VTE recurrence and 87.3 ml/min in patients that did not experience a VTE recurrence. Also, the Caravaggio study did not include patients with creatinine clearance lower than 30 ml/min [3,6].
Conclusion
Finally, the risk factors for VTE recurrence and bleeding showed limited overlapping. The Eastern Cooperative Oncology Group (ECOG) performance status was the only risk factor in common: an ECOG performance status of 2 resulted in a risk factor for bleeding, while an ECOG performance status of 1 or greater emerged as a risk for recurrence [3].
This lack of overlap between risk factors for recurrence and bleeding could facilitate the development of improved risk scores for recurrence or bleeding and the overall risk–benefit of anticoagulant treatment [3].
References
- Sakamoto J, Yamashita Y, Morimoto T, et al. Cancer-Associated Venous Thromboembolism in the Real World – From the COMMAND VTE Registry. Circ J. 2019;83(11):2271-2281. doi:10.1253/circj.CJ-19-0515
- Prandoni P, Lensing AW, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484-3488. doi:10.1182/blood-2002-01-0108
- Vedovati MC, Giustozzi M, Munoz A, et al. Risk factors for recurrence and major bleeding in patients with cancer-associated venous thromboembolism. Eur J Intern Med. 2023;S0953-6205(23)00038-9. doi:10.1016/j.ejim.2023.02.003
- Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005;6(6):401-410. doi:10.1016/S1470-2045(05)70207-2
- Becattini C, Di Nisio M, Franco L, Lee A, Agnelli G, Mandalà M. Treatment of venous thromboembolism in cancer patients: The dark side of the moon. Cancer Treat Rev. 2021;96:102190. doi:10.1016/j.ctrv.2021.102190
- Agnelli G, Becattini C, Meyer G, et al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020;382(17):1599-1607. doi:10.1056/NEJMoa1915103