Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants

Table 1 Baseline characteristics of oral anticoagulant users, warfarin users, direct oral anticoagulants users, and controls not taking any antithrombotic drugs (n = 436) n (%)

Factors	Controls(n = 218)	AC users(n = 218)	P valueControl vs AC users	Warfarin users(n = 145)	P valueControl vs warfarin users	DOAC users(n = 73)	P valueControl vs DOAC users
Age ≥ 75 yr	104 (47.1)	113 (51.8)	0.389	79 (54.5)	0.206	34 (46.6)	0.867
Male	157 (72.0)	157 (72.0)	1.000	103 (71.0)	0.839	54 (74.0)	0.746
BMI ≥ 25	54 (24.8)	69 (31.7)	0.110	44 (30.3)	0.241	25 (34.2)	0.115
Drinker	119 (54.6)	131 (62.1)	0.115	77 (55.4)	0.881	54 (75.0)	0.002
Smoker	36 (16.5)	32 (14.8)	0.626	21 (14.6)	0.622	11 (15.3)	0.805
Laboratory data
Platelet < 10 × 104 μL	6 (2.8)	5 (2.3)	1.000	3 (2.1)	1.000	2 (2.7)	1.000
Ccr < 30 mL/min	9 (4.1)	24 (11.0)	0.007	20 (13.8)	0.001	4 (5.48)	0.743
Comorbidities
Diabetes mellitus	45 (20.6)	52 (23.9)	0.420	39 (26.9)	0.166	13 (17.8)	0.600
Hypertension	121 (55.5)	148 (67.9)	0.008	94 (64.8)	0.077	54 (74.0)	0.005
Dyslipidemia	74 (33.9)	102 (46.8)	0.006	67 (46.2)	0.019	35 (48.0)	0.037
Chronic kidney disease	49 (22.5)	37 (17.0)	0.149	32 (22.1)	0.927	5 (6.9)	0.003
Abnormal liver function	15 (6.9)	8 (3.7)	0.134	3 (2.1)	0.047	5 (6.9)	0.993
Stroke	10 (4.6)	47 (21.6)	< 0.001	29 (20.0)	< 0.001	18 (24.7)	< 0.001
Bleeding past history	21 (9.6)	13 (6.0)	0.153	10 (6.9)	0.361	3 (4.1)	0.217
Chronic heart failure	1 (0.5)	56 (25.7)	< 0.001	46 (31.7)	< 0.001	10 (13.7)	< 0.001
Vascular disease	6 (2.8)	56 (25.7)	< 0.001	49 (33.8)	< 0.001	7 (9.6)	0.014
Acute coronary syndrome	6 (2.8)	34 (15.6)	< 0.001	28 (19.3)	< 0.001	6 (8.2)	0.042
Pulmonary embolism	0 (0.0)	7 (3.2)	0.008	6 (4.1)	0.004	1 (1.4)	0.251
Peripheral arterial disease	0 (0.0)	7 (3.2)	0.008	6 (4.1)	0.004	1 (1.4)	0.251
Deep vein thrombosis	0 (0.0)	14 (6.4)	< 0.001	14 (9.7)	< 0.001	0	NA
Advanced carcinoma	7 (3.2)	33 (15.1)	< 0.001	21 (14.5)	< 0.001	12 (16.4)	< 0.001
Medications
Antiplatelet	0 (0.0)	53 (24.3)	< 0.001	43 (30.0)	< 0.001	10 (13.7)	< 0.001
Low-dose aspirin	0 (0.0)	40 (18.4)	< 0.001	33 (22.8)	< 0.001	7 (9.6)	< 0.001
Thienopyridine1	0 (0.0)	5 (2.3)	0.025	5 (3.5)	0.006	0 (0.0)	NA
Other antiplatelets2	0 (0.0)	11 (5.1)	0.001	8 (5.5)	< 0.001	3 (4.1)	0.003
NSAIDs	21 (9.6)	7 (3.2)	0.006	3 (2.1)	0.004	4 (5.5)	0.341
Endoscopic factors
Number of polyps	2.0 ± 1.4	8.3 ± 5.3	0.019	2.4 ± 1.8	0.063	2.5 ± 1.8	0.041
Number of polyps ≥ 5	13 (6.0)	28 (12.8)	0.014	17 (11.7)	0.078	11 (15.1)	0.014
Polyp size	6.0 ± 3.3	6.3 ± 3.4	< 0.001	8.7 ± 5.9	< 0.001	7.4 ± 3.7	0.001
Polyp size ≥ 10 mm	28 (12.8)	69 (31.7)	< 0.001	47 (32.4)	< 0.001	22 (30.1)	0.001
Advanced adenoma3	27 (12.4)	64 (29.4)	< 0.001	43 (29.7)	< 0.001	21 (28.8)	0.001

¹Thienopyridine includes ticlopidine, clopidogrel, and prasugrel;

²Other antiplatelets are antiplatelets other than low-dose aspirin and thienopyridine;

³Advanced adenoma is adenoma ≥ 1 cm with villous components (tubulovillous or villous) or high-grade or severe dysplasia. Values in parentheses are percentages. Values presented with a plus/minus sign are means ± SD. Bold type indicates statistical significance (P < 0.05). AC: Anticoagulant; DOAC: Direct oral anticoagulants; BMI: Body mass index; Ccr: Creatinine clearance; NSAIDs: Non-steroidal anti-inflammatory drugs.

Table 2 Crude and adjusted odds ratios for post-polypectomy bleeding in controls (n = 218), anticoagulant users (n = 218), warfarin users (n = 145), and direct oral anticoagulants users (n = 73)

Subjects	Crude OR (95%CI)	P value	Propensity score-adjusted OR1 (95%CI)	P value
Controls	1 (referent)		1 (referent)
AC users	17.2 (4.1-73.1)	< 0.001	18.9 (4.2-85.5)	< 0.001
Warfarin users	17.3 (4.0-75.2)	< 0.001	18.6 (3.8-89.9)	< 0.001
DOAC users	17.1 (3.7-80.3)	< 0.001	17.8 (3.2-98.8)	0.001

¹Propensity score estimations. Values in parentheses are percentages. Values presented with a plus/minus sign are means ± SD; bold type indicates statistical significance (P < 0.05). AC users vs controls: Logistic regression model included 17 factors that are potentially clinically important variables; area under the receiver operating characteristic (ROC) curve for propensity scores for AC users was 0.81 (95%CI: 0.77-0.85); Warfarin users vs controls: Logistic regression model included 18 factors that are potentially clinically important variables; area under the ROC curve for propensity scores for warfarin users was 0.83 (95%CI: 0.78-0.88); DOAC users vs controls: Logistic regression model included 14 factors that are potentially clinically important variables; area under the ROC curve for DOAC user propensity scores was 0.85 (95%CI: 0.80-0.90). NA: Not applicable; AC: Anticoagulants; DOAC: Direct oral anticoagulants; HPB: Heparin bridge; OR: Odds ratio.

Table 3 Crude and adjusted odds ratios for post-polypectomy bleeding in anticoagulant users (n = 218), warfarin users (n = 145), and direct oral anticoagulants users (n = 73)

AC management during peri-endoscopic period	Crude OR (95%CI)	P value	Propensity score-adjusted OR1 (95%CI)	P value
AC users
Discontinuing AC with HPB vs continuing AC	2.0 (0.9-4.6)	0.091	2.2 (0.9-5.2)	0.069
Discontinuing AC with HPB vs discontinuing AC without HPB	7.7 (1.3-Inf)	0.023	NA	NA
Warfarin users
Discontinuing warfarin with HPB vs continuing warfarin	5.7 (1.3-25.8)	0.024	4.7 (1.0-22.1)	0.049
Discontinuing warfarin with HPB vs discontinuing warfarin without HPB	7.2 (1.1-Inf)	0.033	NA	NA
DOAC users
Discontinuing DOAC with HPB vs continuing DOAC	0.6 (0.1-3.2)	0.567	0.7 (0.1-4.5)	0.664
Discontinuing DOAC with HPB vs discontinuing DOAC without HPB	0.5 (0.4-Inf)	1.000	NA	NA

¹Propensity score estimations. Values in parentheses are percentages. Values presented with a plus/minus sign are means ± SD; bold type indicates statistical significance (P < 0.05). Continuing AC group vs standard group: Logistic regression model included 8 factors that are potentially clinically important variables; area under the ROC curve for propensity scores for the continuing AC group was 0.71 (95%CI: 0.63-0.79); standard group vs continuing warfarin group: Logistic regression model included 6 factors that are potentially clinically important variables; area under the ROC curve for propensity scores for the continuing warfarin group was 0.63 (95%CI: 0.53-0.73); standard group vs continuing DOAC group: Logistic regression model included 6 factors that are potentially clinically important variables; area under the ROC curve for propensity scores for the continuing DOAC group was 0.90 (95%CI: 0.82-0.98). NA: Not applicable; AC: Anticoagulants; CI: Confidential interval; DOAC: Direct oral anticoagulants; HPB: Heparin bridge; Inf: Infinity; OR: Odds ratio.