Direct Oral Anticoagulants Are Associated with Superior Survival Outcomes than Warfarin in Patients with Head and Neck Cancers

Abstract

Increasing clinical evidence supports the use of direct oral anticoagulants (DOACs) as a potential new therapeutic option for patients suffering from cancer-associated thromboembolism. However, the clinical impact of DOACs compared with traditional anticoagulants on the survival of patients with head and neck cancer has not been well studied. A total of 1025 patients diagnosed as having head and neck cancer, including 92 DOAC users, 113 warfarin users, and 820 nonusers of anticoagulants, were selected from the Chang Gung Research Database between January 2001 and December 2019. The patients were matched using the propensity-score method. The survival rates were estimated among the three groups using the Kaplan–Meier method. The protective effects and side effects of the two anticoagulants were compared using the chi-square test. The death rate (18 patients, 19.57%) in patients using DOACs was significantly lower than that in patients using warfarin (68 patients, 60.18%) and those not using any anticoagulant (403 patients, 49.15%). DOAC users had significantly better disease-specific survival (DSS) than warfarin users (p = 0.019) and those who did not use any anticoagulant (p = 0.03). Further, DOAC users had significantly higher overall survival (OS) rates than warfarin users and those who did not use any anticoagulant (p = 0.003). Patients with oropharyngeal and laryngeal cancer and DOAC users had a significantly lower hazard ratio for survival, whereas patients with American Joint Committee on Cancer stage IV disease and those receiving multidisciplinary treatment (e.g., surgery with radiotherapy or concurrent radiochemotherapy) had a significantly higher hazard ratio for survival. Among them, patients with laryngeal cancer (HR = 0.47, 95% CI = 0.26–0.86, p = 0.0134) and DOAC users (HR = 0.53, 95% CI = 0.29–0.98, p = 0.042) had the lowest hazard ratio from DSS analysis. Similarly, patients with laryngeal cancer (HR = 0.48, 95% CI = 0.30–0.76, p = 0.0018) and DOAC users (HR = 0.58, 95% CI = 0.36–0.93, p = 0.0251) had the lowest hazard ratio from OS analysis. As for the protective effects or side effects of anticoagulants, there were no significant differences in the occurrence rate of bleeding or ischemic events between DOAC and warfarin users. In our study, DOACs were found to be better than warfarin in terms of survival in patients with head and neck cancer. As regards thromboembolism prevention and side effects, DOACs were comparable to warfarin in our patients. DOACs can be a treatment choice or prophylaxis for tumor emboli in head and neck cancer patients and they might be a better choice than traditional anticoagulants according to the results of our study.

Vascular events in patients with head and neck cancer: A systematic review and meta‐analysis

“…17 However, that same study noted that survival of patients on DOACs was superior to that of those on warfarin, hinting that the specific type of anticoagulation could play a role in outcomes. 17 The American Society of Clinical Oncology recommends thromboprophylaxis with heparin derivatives preoperatively and for at least 1 week after surgery for all patients with cancer receiving surgery. 18 It should be noted that anticoagulant use in the postoperative period after head and neck surgery can be controversial due to balancing the risks of thrombosis versus bleeding.…”

“…The use of anticoagulation is inconsistent when it comes to chemoprophylaxis in patients with HNC. A database study in 2022, including patients taking anticoagulation for various indications, found that disease‐specific survival was superior for patients with HNC taking direct oral anticoagulants (DOACs) compared to warfarin and those not taking any anticoagulant, suggesting that some element of anticoagulation is protective for this population 17 . However, that same study noted that survival of patients on DOACs was superior to that of those on warfarin, hinting that the specific type of anticoagulation could play a role in outcomes 17 .…”

“…A database study in 2022, including patients taking anticoagulation for various indications, found that disease‐specific survival was superior for patients with HNC taking direct oral anticoagulants (DOACs) compared to warfarin and those not taking any anticoagulant, suggesting that some element of anticoagulation is protective for this population 17 . However, that same study noted that survival of patients on DOACs was superior to that of those on warfarin, hinting that the specific type of anticoagulation could play a role in outcomes 17 . The American Society of Clinical Oncology recommends thromboprophylaxis with heparin derivatives preoperatively and for at least 1 week after surgery for all patients with cancer receiving surgery 18 .…”