Comparative Outcomes of Peripheral Vascular Intervention in Patients on Chronic Anticoagulation With Factor Xa Inhibitors and Vitamin K Antagonists

Abstract

Factor Xa inhibitors (FXaI) have been shown to improve the outcomes of patients with peripheral arterial disease (PAD) compared to aspirin alone. Further, FXaI have become preferred over vitamin K antagonists (VKA) for chronic anticoagulation in various diseases such as venous thromboembolism and atrial fibrillation. However, the impact of FXaI use on the outcomes of patients with PAD on chronic anticoagulation undergoing peripheral vascular interventions (PVI) has not been studied. This project compares the perioperative and long-term outcomes of PVI in patients with PAD chronically anticoagulated with FXaI and VKA. The Vascular Quality Initiative database for PVI was reviewed. Patients treated for PAD with consistent use of FXaI or VKA prior to procedure, at discharge, and on long-term follow-up were defined as patients who were chronically anticoagulated. Patient and procedural characteristics and outcomes were compared between patients on FXaI and VKA. Kaplan-Meier amputation-free survival analysis and Cox proportional hazard regression were performed to evaluate long-term outcomes. A total of 148,841 PVI were reviewed and 6.6% were chronically anticoagulated with one of the selected agents. Chronic anticoagulation with VKA (66.4%; n = 6481) was more common than FXaI (33.6%; n = 3274). Patients receiving VKA were more frequently males (64.7% vs 60.6%; P < .001) with end-stage renal disease (10.7% vs 5.0%; P < .001). PVI was also performed more commonly in urgent cases (17.1% vs 15.1%; P = .013) and for chronic limb-threatening ischemia (58.6% vs 53.8%; P < .001) in patients receiving VKA. Patients on VKA had significantly higher hematoma rate after PVI compared to patients on FXaI (3.4% vs 1.9%; P < .001). Patients on FXaI were also significantly more likely to be discharged home and had shorter hospital length of stay (Table). Multivariable regression demonstrated that VKA use was independently associated with increased rates of hematoma compared to FXaI (odds ratio, 1.77; 95% confidence interval, 1.29-2.47). On follow-up, patients treated with FXaI had lower rates of major amputation (6.9% vs 8.5%; P = .011) and mortality (9.3% vs 16.9%; P ≤ .001) compared to patients receiving VKA. Kaplan-Meier analysis demonstrated that patients on FXaI had improved amputation-free survival after PVI compared to VKA (Figure). Cox proportional hazard regression showed that VKA were independently associated with major amputation or mortality (hazard ratio, 1.48; 95% confidence interval, 1.30-1.69). In patients with PAD on chronic anticoagulation, FXaI were associated with improved outcomes of PVI compared to VKA. FXaI should be considered the agent of choice for chronic anticoagulation in patients with PAD when indicated.TablePatient characteristics, procedural characteristics, and outcomesCharacteristicFactor Xa inhibitor, n = 3274 (33.6%)Vitamin K antagonist, n = 6481 (66.4%)P valueaPatient characteristics Age, years70 ± 1171 ± 11<.001* Male1983 (60.6)4192 (64.7)<.001* Race.473White2699 (82.4)5402 (83.4)African American432 (13.2)802 (12.4)Other143 (4.4)273 (4.2) Body mass index29 ± 629 ± 6.774 Body mass index class.851Normal weight1915 (58.6)3837 (59.3)Obese1095 (33.5)2130 (32.9)Morbidly obese178 (5.4)337 (5.2)Underweight80 (2.4)167 (2.6) Living status.501Home3123 (95.4)6204 (95.7)Nursing home/homeless149 (4.6)276 (4.3) Ambulatory status.493Assisted834 (25.8)1663 (25.9)Independent2176 (67.2)4276 (66.5)Nonambulatory227 (7.0)493 (7.7) Hypertension2958 (90.9)5904 (91.2).553 Diabetes1734 (53.0)3492 (53.9).386 Smoking (former or current)2522 (77.1)4859 (75.0).024* Chronic obstructive pulmonary disease977 (29.9)1823 (28.1).077 Cerebrovascular disease584 (19.7)603 (20.5).439 History of percutaneous coronary intervention895 (27.4)1616 (26.1).183 Coronary artery disease1284 (39.2)2545 (39.3).971 Congestive heart failure1008 (30.8)2139 (33.0).027* History of dysrhythmia1652 (56.0)1623 (55.3).598 History of coronary artery bypass grafting737 (22.5)1768 (28.5)<.001* History of carotid intervention (carotid artery stenting/carotid endarterectomy)299 (9.1)608 (9.8).278 History of aneurysm147 (4.5)318 (4.9).367 Renal status<.001Normal function550 (17.2)972 (15.2)Chronic kidney disease2493 (77.8)4735 (74.1)End-stage renal disease161 (5.0)684 (10.7) History of lower extremity revascularization1976 (60.4)4012 (61.9).147 History of lower extremity amputation567 (17.3)1326 (20.5)<.001* Aspirin1754 (53.6)3734 (57.6)<.001* P2Y12 inhibitor1049 (32.0)1844 (28.5)<.001* Statin2532 (77.3)4885 (75.4).032* Angiotensin-converting enzyme inhibitor1756 (53.6)3201 (51.7).080 Cilostazol144 (4.9)125 (4.3).263Factor Xa inhibitor, N = 3274 (33.6%)Vitamin K antagonist, n = 6481 (66.4%)P valueaProcedural characteristics Indication<.001*Claudication1299 (46.2)2289 (41.4)Chronic limb-threatening ischemia1510 (53.8)3238 (58.6) Urgency.013*Elective2779 (84.9)5367 (82.9)Urgent/emergent494 (15.1)1105 (17.1) Laterality.729Left1484 (49.7)2970 (49.3)Right1500 (50.3)3049 (50.7) Fluoroscopy time19 ± 1719 ± 15.773 Contrast volume, mL75 (45-115)72 (44-115).066 Procedural anticoagulant.588None84 (2.8)95 (3.2)Heparin2825 (95.4)2799 (95.3)Bivalirudin46 (1.6)36 (1.2)Other7 (0.2)7 (0.2) Protamine790 (25.3)1396 (22.1).001* Treatment type<.001*Balloon angioplasty1327 (40.5)2870 (44.3)Stenting1281 (39.1)2596 (40.1)Atherectomy484 (14.8)740 (11.4)Atherectomy and stenting182 (5.6)275 (4.2)Factor Xa inhibitor, n = 3274 (33.6%)Vitamin K antagonist, n = 6481 (66.4%)P valueaPeriprocedural outcomes Technical success2969 (93.8)5881 (94.1).599 ComplicationsCardiac32 (1.1)44 (1.5).155Myocardial infarction8 (0.3)16 (0.5).098Pulmonary14 (0.5)12 (0.4).710Renal18 (0.6)31 (1.1).058Serious contrast reaction0 (0)1 (<0.1).498Embolism17 (0.6)15 (0.5).740Artery perforation19 (0.6)17 (0.6).757Hematoma61 (1.9)223 (3.4)<.001*Infection3 (0.1)5 (0.2).506Pseudoaneurysm7 (0.2)9 (0.3).605Thrombosis, at target lesion22 (0.7)16 (0.5).342Dissection, at target lesion59 (2.0)49 (1.7).353 Discharge status<.001*Home2977 (91.0)5721 (88.4)Rehab unit119 (3.6)381 (5.9)Other174 (5.3)372 (5.7) Length of stay, days3 (13)4 (18)<.001* 30-Day mortality13 (0.4)33 (0.5).446Factor Xa inhibitor, n = 3274 (33.6%)Vitamin K antagonist, n = 6481 (66.4%)P valueaLong-term outcomes Reintervention545 (17.7)1021 (17.1).451 Amputation198 (6.9)480 (8.5).011* Major adverse limb events708 (22.4)1382 (22.3).950 Mortality304 (9.3)1097 (16.9)<.001* Mean follow-up time, days388 (129)393 (144).181Values are number (%), mean ± standard deviation, or median (interquartile range).Boldface entries indicate statistical significance.aPearson's χ2; Fisher's exact test; Wilcoxon rank-sum test. 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