Introduction

Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Heparin bridge (HB) is a standard therapy for polypectomy in patients taking warfarin, however, a reported high incidence of post-polypectomy bleeding (PPB) and prolonged hospitalization have been critical problems. We hypothesized that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin administration (CWA) is not inferior to endoscopic colorectal polypectomy under standard treatment with HB therapy with respect to the rate of PPB.

Aims & Methods

We conducted a prospective multicenter randomized controlled non-inferiority trial comparing PPB between CWA and HB. Patients taking warfarin who would undergo colorectal polypectomy were eligible for inclusion. Enrolled patients were assigned to the CWA and HB groups in a 1 to 1 ratio and underwent polypectomy using electrocautery. The primary outcome measure was the PPB rate within 28 days: 1) bloody stool with haemoglobin decrease of 2 g/dL or more, 2) overt bloody stool required endoscopic haemostasis, angiography, surgery, and/or blood transfusion. The major secondary outcomes included the rate of cumulative bleeding, minor bleeding, intra-operative bleeding requiring haemostasis, bleeding requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery.

Results

From October 2016 to July 2021, a total of 325 patients were assessed eligibility and, 316 were enrolled and underwent randomized. After 7 and 10 patients were excluded, 151 and 148 in CWA and HB group were analyzed as a full analysis set. PPB occurred 7.9% in CWA and 23.6% in the HB group, respectively. The intergroup difference for the primary outcome was -15.7% (95%CI; -24.0% to -7.7%), which was lower than the pre-set non-inferiority margin of 5% (p<0.001). Minor bleeding. intra-operative bleeding, and total bleeding occurred 1.3% and 4.7%, 9.3% and 9.5%, and 17.9% and 29.7% in CWA and HB group while one patient in HB group required blood transfusion (0.7%). The median hospitalization period was 3 days in CWA and 13 days in the HB group (p<0.001). No thromboembolism occurred. PT-INR of 28 days after the surgery were 1.92 and 1.50, respectively.

Conclusion

In patients receiving warfarin therapy, CWA did not show an increased occurrence of PPB and resulted in shorter hospitalization period compared to the conventional HB therapy.

Disclosure

The trial was supported by the Japanese Gastroenterological Association Foundation.
Yasuaki Nagami has received lecture honoraria from Olympus, Takeda Pharmaceutical Company, EA Pharma, Otsuka Pharmaceutical Company and Daiichi-Sankyo Co.
Takuji Gotoda has received honoraria from Olympus, Fujifilm Corporation, Fujifilm medical, MC Medical, Boston Scientific, Takeda Pharmaceutical Company, Astra Zeneca Pharmaceuticals, EA Pharma, 3D matrix, Century medical, Mochida Pharmaceutical, Zeria Pharmaceutical, Viatris, and AIM.
Motohiko Kato has received honoraria from Olympus, Fujifilm, Boston Scientific, Takeda Pharmaceutical Company, and EA Pharma
Kenichiro Imai has received honoraria from Olympus, Boston Scientific, Takeda Pharmaceutical Company, EA Pharma, 3D matrix, Otsuka Pharmaceutical Company, KANEKA Corporation, Kaigen-pharma, TOP Corporation and received a research grant from KANEKA Corporation and the Japanese Foundation for research and promotion of endoscopy.
Yoji Takeuchi has received honoraria from Olympus, Boston Scientific, Takeda Pharmaceutical Company, EA Pharma, Zeria Pharmaceutical, and Viatris
Sho Suzuki has received honoraria for his lectures from Fujifilm Corporation, MC Medical, Inc, and Olympus Corporation.
Yoshihide Naito received honoraria from Takeda Pharmaceutical Company, Daiichi-Sankyo Co., Janssen Pharmaceutical K.K., Abbvie, Mitsubishi Tanabe Pharma Corporation, and Asahikasei-pharma.co.
Takuji Kawamura received honoraria from Olympus Corporation for lectures, presentations, or educational events.
Takumi Imai received lecture fees from JCR Pharmaceuticals and KyowaKirin.
Yasuhiro Fujiwara has received lecture honoraria from Takeda Pharmaceutical Co., EA Pharma Co., Astra Zeneca Pharmaceuticals, Otsuka Pharmaceuticals., and Daiichi-Sankyo Co., Advisor fees from Asteras Pharma., research grants from EA Pharma Co.