Abstract
Background:
Intermittent claudication (IC) is a commonly treated vascular condition. Patient sex has been shown to influence outcomes of interventions for other vascular disorders; however, whether outcomes of interventions for IC vary by sex is unclear. We sought to assess the association of patient sex with outcomes after IC interventions.
Methods:
The Vascular Quality Initiative was queried from 2010–2020 for all peripheral endovascular interventions (PVI), infra-inguinal bypasses (IIB), and supra-inguinal bypasses (SIB) for any degree IC. Univariable and multivariable analyses compared peri-operative and long-term outcomes by patient sex.
Results:
There were 24,701 female and 40,051 male patients undergoing PVI, 2,789 female and 6,525 male patients undergoing IIB, and 1,695 female and 2,370 male patients undergoing SIB for IC. Guideline-recommended pre-operative medical therapy differed with female patients less often prescribed aspirin for PVI (73.4% vs. 77.3%), IIB (71.5% vs. 74.8%), and SIB (70.9% vs. 74.3%) or statins for PVI (71.8% vs. 76.7%) and IIB (73.1% vs. 76.0%) (all P < 0.05). Female compared with male patients had lower 1-year reintervention-free survival after PVI (84.4% ± 0.3% vs. 86.3% ± 0.2%, P < 0.001), IIB (79.0% ± 0.9% vs. 81.2% ± 0.6%, P = 0.04), and SIB (89.4% ± 0.9% vs. 92.6% ± 0.7%, P = 0.005), but similar amputation-free survival and survival across all procedures. Multivariable analysis confirmed that female sex was associated with increased 1-year reintervention for PVI (HR 1.16, 95% CI 1.09–1.24, P < 0.001), IIB, (HR 1.16, 95% CI 1.03–1.31, P = 0.02), and SIB (HR 1.60, 95% CI 1.20–2.13, P = 0.001).
Conclusions:
Female patients undergoing interventions for IC were less often pre-operatively medically optimized than male patients, though the difference was small. Furthermore, female sex was associated with more reinterventions after interventions. Interventionists treating female patients should increase their efforts to maximize medical therapy. Future research should clarify reasons for poorer intervention durability in female patients.
INTRODUCTION
Intermittent claudication (IC) is 1 of the more common vascular conditions evaluated by vascular surgeons for both nonoperative and operative treatment.1–5 Initial treatment includes medical optimization, exercise therapy, and smoking cessation.1–6 The Society for Vascular Surgery (SVS) and European Society of Cardiology/European Society for Vascular Surgery (ESC/ESVS) guidelines recommend reserving interventions for those refractory to noninvasive management.1,7 Interventions offered should provide durable clinical improvement for at least 2 years in over half of patients.1 Inadequate medical optimization is associated with worse outcomes after IC interventions.6,8 Interventions for IC are susceptible to overuse, which in turn may result in adverse outcomes, including limb loss.8
Patient sex influences outcomes after open and endovascular interventions for variety vascular conditions.9–13 Female sex is associated with worse outcomes of abdominal aortic aneurysm repair, thoracic aorta stent graft placement, and carotid artery interventions.10–13 However, whether outcomes after IC treatment vary by patient sex is unclear. Previous studies evaluating interventions for peripheral arterial disease by sex broadly included patients with both IC and chronic limb-threatening ischemia (CLTI).14–17 Furthermore, sex-related differences in outcomes of peripheral arterial disease (PAD) interventions, including reintervention, amputation, and mortality, have been conflicting.14–17
Our goal was to assess whether pre-operative medical optimization and post-operative outcomes, both peri-operative and at 1 year, for IC interventions vary by patient sex. We used the Vascular Quality Initiative (VQI) database as it provides granular pre-operative and procedural details, long-term outcomes, and a sufficient number of interventions for analysis. Endovascular peripheral vascular intervention (PVI), infra-inguinal bypass (IIB), and supra-inguinal bypass (SIB) registries were analyzed.
METHODS
The VQI was queried from 2010–2020 for all PVI, IIB, and SIB performed for any degree of IC. These registries provide demographics, comorbidities, procedural details, and peri-operative/long-term outcomes for patients undergoing interventions in over 800 academic and nonacademic centers in North America. Both surgeons and clinical abstractors at the individual centers prospectively collected these data which are routinely audited by the VQI. The Boston University Institutional Review Board classified this research as nonhuman subject research. The VQI National Research Advisory Committee approved this study.
Patients were stratified by sex as documented in the database. Interventions for acute limb ischemia, CLTI, and aneurysms were excluded. Bypass details, conduit type, and concomitant procedures were recorded. Patient demographics included age, race, pre-admission living status, primary insurer, smoking status, and ambulatory status (ambulatory without assistance, ambulatory with assistance of a cane/walker, nonambulatory [wheelchair/bed-bound]). Comorbidities included obesity (body mass index [BMI] ≥ 30 kg/m2), hypertension, coronary artery disease (CAD), congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), diabetes, anemia (hemoglobin <10 g/dL), end-stage renal disease (ESRD), previous inflow or outflow interventions (open or endovascular), as well as pre-operative and discharge aspirin, statin, P2Y12 inhibitor, and anticoagulant use.
Peri-operative outcomes analyzed were postoperative length of stay (LOS), return to the operating room, pulmonary complications (pneumonia or unplanned intubation), decreased renal function (creatinine increase >0.5 mg/dL, temporary/permanent dialysis), cardiac complications (new postoperative dysrhythmia, CHF, myocardial infarction), and 30-day mortality. One-year outcomes included freedom from reinterventions/death, major amputation/death, and death. Given that patients may have died before developing complications, we included death in the composite outcomes to avoid underestimating complications.
Statistical Analysis
Patient demographics, procedural characteristics, and outcomes were reported as categorical variables, n (%), or continuous variables, mean ± standard deviation, as appropriate. Univariable and multivariable analyses were performed to evaluate for differences between male and female sex. Demographics, operative details, and peri-operative outcomes were compared using t-test for continuous measures and Chi-square test for categorical measures. Kaplan-Meier analyses and log-rank tests compared 1-year outcomes between cohorts. Multivariable Cox proportional hazards models determined associations with outcomes adjusted for confounding factors. All multivariable models included variables found to have P-value <0.2 on unadjusted analyses. Then, backward elimination procedure (with alpha level = 0.5) was used to create more parsimonious models. The relationships were expressed as hazard ratios (HR) with corresponding 95% confidence intervals (CI). A P-value < 0.05 was set as statistically significant. All analyses were performed using SAS 9.3 software (SAS Institute Inc, Cary, NC).
RESULTS
Demographics and Comorbidities
There were 64,752 PVI (61.9% male sex, 38.1% female sex), 9,314 (70.1% male sex, 29.9% female sex) IIB, and 4,065 SIB (58.3% male sex, 41.7% female sex) performed for IC from 2010–2020. Across all procedures, female compared with male patients were more likely to be never-smokers and have Medicare insurance. For PVI and IIB, female patients were more often Black/African American and less often actively smoking (Tables I–II). When analyzing comorbidities across all 3 procedures, female patients were more likely to be obese, ambulatory with assistance; more often had COPD and anemia; and less often had CAD and previous coronary revascularization.
Table I.
Demographics and comorbidities of patients undergoing peripheral vascular interventions for intermittent claudication
| Characteristic | Female sex (n = 24,701) | Male sex (n = 40,051) | P |
|---|---|---|---|
|
| |||
| Age – y | 68.1 ± 10.9 | 66.5 ± 10.0 | <0.001 |
| Race | |||
| Native American/Alaskan Native | 76 (0.3) | 104 (0.3) | <0.001 |
| Asian | 174 (0.7) | 344 (0.9) | |
| Black/African American | 3,609 (14.6) | 4,060 (10.1) | |
| Native Hawaiian/Pacific Islander | 17 (0.1) | 29 (0.1) | |
| White | 19,967 (80.9) | 33,987 (84.9) | |
| More than 1 race | 29 (0.1) | 59 (0.1) | |
| Hispanic ethnicity | 1,037 (4.2) | 1,578 (4.0) | 0.11 |
| Body mass index | 28.0 ± 7.3 | 28.1 ± 5.4 | 0.010 |
| Obese | 8,262 (33.6) | 12,896 (32.3) | 0.001 |
| Prior smoking | 10,608 (43.0) | 19,627 (49.1) | <0.001 |
| Current smoking | 9,682 (39.3) | 16,554 (41.4) | <0.001 |
| Primary payer | |||
| Medicare | 12,391 (54.7) | 17,937 (48.6) | <0.001 |
| Medicaid | 1,422 (6.3) | 2,257 (6.1) | |
| Commercial | 8,437 (37.2) | 15,643 (42.4) | |
| Ambulatory with assistance | 2,634 (10.8) | 2,983 (7.5) | <0.001 |
| Living at home | 24,334 (99.2) | 39,550 (99.5) | <0.001 |
| Hypertension | 21,432 (86.8) | 34,567 (86.4) | 0.10 |
| Diabetes | 9,562 (38.8) | 16,219 (40.5) | <0.001 |
| Dialysis/transplanted kidney | 657 (2.7) | 1,097 (2.7) | 0.55 |
| Chronic obstructive pulmonary disease | 7,313 (29.6) | 9,907 (24.8) | <0.001 |
| Coronary artery disease | 6,694 (27.1) | 13,918 (34.8) | <0.001 |
| Congestive heart failure | 2,906 (11.8) | 4,880 (12.2) | 0.11 |
| Percutaneous coronary intervention | 5,025 (22.1) | 10,350 (28.0) | <0.001 |
| Coronary artery bypass graft | 3,047 (13.4) | 8,675 (23.5) | <0.001 |
| Inflow peripheral endovascular intervention | 3,501 (14.3) | 5,649 (14.2) | 0.78 |
| Inflow bypass | 910 (3.7) | 1,604 (4.0) | 0.042 |
| Prior leg peripheral endovascular intervention | 5,017 (20.5) | 8,253 (20.8) | 0.38 |
| Prior leg bypass | 1,901 (7.8) | 3,759 (9.5) | <0.001 |
| Prior major leg amputation | 661 (2.7) | 1,325 (3.3) | <0.001 |
| Pre-operative anemia | 769 (6.8) | 729 (4.0) | <0.001 |
| Pre-operative creatinine – mg/dL | 1.0 ± 0.5 | 1.1 ± 0.5 | <0.001 |
| Pre-operative aspirin | 18,128 (73.4) | 30,927 (77.3) | <0.001 |
| Pre-operative P2Y12 inhibitor | 9,572 (38.8) | 15,693 (39.2) | 0.27 |
| Pre-operative anticoagulant | 2,427 (9.8) | 4,542 (11.4) | <0.001 |
| Pre-operative statin | 17,726 (71.8) | 30,707 (76.7) | <0.001 |
Data are presented as n (%) or mean ± standard deviation.
Table II.
Demographics and comorbidities of patients undergoing infrainguinal and suprainguinal bypass for intermittent claudication
| Infrainguinal bypass |
Suprainguinal bypass |
|||||
|---|---|---|---|---|---|---|
| Characteristic | Female sex (n = 2,789) | Male sex (n = 6,525) | P | Female (n = 1,695) | Male (n = 2,370) | P |
|
| ||||||
| Age – y | 65.9 ± 10.6 | 64.8 ± 9.8 | <0.001 | 60.6 ± 9.6 | 60.5 ± 8.8 | 0.72 |
| Race | ||||||
| Native American/Alaskan Native | 8 (0.3) | 17 (0.3) | <0.001 | 7 (0.4) | 4 (0.2) | 0.46 |
| Asian | 8 (0.3) | 30 (0.5) | 10 (0.6) | 23 (1.0) | ||
| Black/African American | 442 (15.9) | 727 (11.1) | 121 (7.2) | 171 (7.2) | ||
| Native Hawaiian/Pacific Islander | 2 (0.1) | 3 (0.05) | 0 (0.0) | 2 (0.1) | ||
| White | 2,245 (80.8) | 5,557 (85.2) | 1,503 (88.9) | 2,105 (88.9) | ||
| More than 1 race | 0 (0.0) | 5 (0.1) | 3 (0.2) | 3 (0.1) | ||
| Hispanic ethnicity | 110 (4.0) | 256 (3.9) | 0.93 | 53 (3.2) | 56 (2.4) | 0.14 |
| Body mass index | 28.1 ± 6.4 | 28.2 ± 5.4 | 0.26 | 26.6 ± 6.0 | 26.5 ± 5.0 | 0.49 |
| Obese | 975 (35.0) | 2,137 (32.8) | 0.040 | 442 (26.1) | 525 (22.2) | 0.004 |
| Prior smoking | 1,235 (44.3) | 3,251 (49.8) | <0.001 | 609 (35.9) | 911 (38.5) | 0.001 |
| Current smoking | 1,146 (41.1) | 2,810 (43.1) | <0.001 | 1,001 (59.1) | 1,388 (58.6) | 0.001 |
| Primary payer | ||||||
| Medicare | 1,215 (49.5) | 2,489 (42.4) | <0.001 | 507 (33.4) | 659 (31.6) | 0.33 |
| Medicaid | 177 (7.2) | 448 (7.6) | 204 (13.4) | 240 (11.5) | ||
| Commercial | 992 (40.4) | 2,731 (46.5) | 736 (48.4) | 1,076 (51.6) | ||
| Ambulatory with assistance | 378 (13.6) | 658 (10.1) | <0.001 | 180 (10.6) | 172 (7.3) | <0.001 |
| Living at home | 2,760 (99.2) | 6,452 (99.2) | 0.095 | 1,683 (99.7) | 2,343 (99.3) | 0.084 |
| Hypertension | 2,427 (87.0) | 5,587 (85.6) | 0.075 | 1,325 (78.5) | 1,875 (79.3) | 0.55 |
| Diabetes | 1,115 (40.0) | 2,463 (37.8) | 0.042 | 454 (26.8) | 519 (21.9) | <0.001 |
| Chronic obstructive pulmonary disease | 824 (29.6) | 1,597 (24.5) | <0.001 | 599 (35.4) | 652 (27.5) | <0.001 |
| Coronary artery disease | 755 (27.1) | 2,003 (30.7) | <0.001 | 348 (20.5) | 563 (23.8) | 0.014 |
| Congestive heart failure | 270 (9.7) | 659 (10.1) | 0.54 | 114 (6.7) | 172 (7.3) | 0.51 |
| CABG/percutaneous coronary intervention | 803 (28.9) | 2,447 (37.5) | <0.001 | 330 (19.5) | 589 (24.9) | <0.001 |
| Inflow peripheral endovascular intervention | 546 (19.6) | 1,278 (19.6) | 0.99 | 344 (20.3) | 423 (17.9) | 0.052 |
| Inflow bypass | 255 (9.2) | 547 (8.4) | 0.23 | 74 (4.4) | 164 (6.9) | 0.001 |
| Leg peripheral endovascular intervention | 1,066 (38.3) | 2,238 (34.4) | <0.001 | 118 (7.0) | 189 (8.0) | 0.23 |
| Leg bypass | 481 (17.3) | 1,199 (18.4) | 0.20 | 58 (3.4) | 120 (5.1) | 0.011 |
| Prior major leg amputation | 29 (1.0) | 65 (1.0) | 0.85 | 5 (0.3%) | 14 (0.6%) | 0.17 |
| Pre-operative anemia | 264 (9.5) | 360 (5.5) | <0.001 | 81 (4.8) | 72 (3.1) | 0.004 |
| Pre-operative creatinine – mg/dL | 0.9 ± 0.5 | 1.1 ± 0.6 | <0.001 | 0.8 ± 0.4 | 1.0 ± 0.4 | <0.001 |
| Pre-operative aspirin | 1,995 (71.5) | 4,882 (74.8) | 0.001 | 1,202 (70.9) | 1,761 (74.3) | 0.016 |
| Pre-operative P2Y12 inhibitor | 1,017 (36.5) | 2,124 (32.6) | <0.001 | 322 (19.0) | 428 (18.1) | 0.46 |
| Pre-operative anticoagulant | 285 (11.6) | 812 (13.8) | 0.006 | 92 (6.0) | 152 (7.2) | 0.15 |
| Pre-operative statin | 2,037 (73.1) | 4,958 (76.0) | 0.003 | 1,257 (74.2) | 1,775 (75.0) | 0.56 |
Data are presented as n (%) or mean ± standard deviation.
CABG, coronary artery bypass graft.
Pre-operative medication differed between female and male patients, with female patients less often prescribed aspirin for PVI (73.4% vs. 77.3%), IIB (71.5% vs. 74.8%), and SIB (70.9% vs. 74.3%) (all P < 0.05), but there was no significant difference for P2Y12 use. Female sex was also associated with less pre-operative statin use in PVI (71.8% vs. 76.7) and IIB (73.1% vs. 76%) (all P < 0.05).
Procedure
For PVI, female sex was associated with more iliac interventions, less femoropopliteal and infrapopliteal interventions, and less stenting and atherectomy compared to male sex (all P < 0.05). For IIB, female patients had fewer below the knee popliteal and tibial targets and more prosthetic conduits. For female patients undergoing SIB, configuration for the abdominal aorta was more often end-to-end with external iliac arteries used more often as targets and profunda arteries used less often as targets (Tables III–V).
Table III.
Procedural details and peri-operative outcomes of peripheral endovascular interventions for intermittent claudication
| Characteristic | Female sex (n = 24,701) | Male sex (n = 40,051) | P |
|---|---|---|---|
|
| |||
| Procedure | |||
| Ultrasound guidance | 14,442 (59.1) | 22,778 (57.5) | <0.001 |
| Sheath size | 6.1 ± 0.7 | 6.2 ± 0.7 | <0.001 |
| Closure device used | 24,652 (99.8) | 39,978 (99.8) | 0.65 |
| Iliac intervention | 11,667 (47.3) | 18,220 (45.6) | <0.001 |
| Femoropopliteal intervention | 14,465 (58.7) | 24,348 (60.9) | <0.001 |
| Infrapopliteal intervention | 2,262 (9.2) | 4,188 (10.5) | <0.001 |
| Angioplasty/plain balloon | 17,679 (71.6) | 28,851 (72.0) | 0.20 |
| Stent/stent graft | 15,343 (62.1) | 25,892 (64.6) | <0.001 |
| Atherectomy | 3,998 (16.2) | 7,001 (17.5) | <0.001 |
| Technical success (stenosis ≤30%) | 23,402 (96.0) | 37,398 (94.6) | <0.001 |
| Discharged on aspirin | 19,969 (81.2) | 33,403 (83.7) | <0.001 |
| Discharged on P2Y12 inhibitor | 18,351 (74.6) | 29,567 (74.1) | 0.18 |
| Discharged on anticoagulant | 2,763 (11.2) | 5,058 (12.7) | <0.001 |
| Discharged on statin | 18,748 (76.2) | 32,251 (80.8) | <0.001 |
| Peri-operative Outcomes | |||
| Any hematoma | 898 (3.6) | 915 (2.3) | <0.001 |
| Any stenosis/occlusion | 74 (0.3) | 70 (0.2) | 0.001 |
| 30-day mortality | 101 (0.4) | 135 (0.3) | 0.14 |
Data are presented as n (%) or mean ± standard deviation.
Table V.
Procedural details and peri-operative outcomes of suprainguinal bypass for intermittent claudication
| Characteristic | Female sex (n = 1,695) | Male sex (n = 2,370) | P |
|---|---|---|---|
|
| |||
| Procedure | |||
| Graft origin artery | |||
| Abdominal aorta, end-side | 690 (40.7) | 1,037 (43.8) | <0.001 |
| Abdominal aorta, end-end | 852 (50.3) | 1,041 (43.9) | |
| Common iliac | 104 (6.1) | 182 (7.7) | |
| External iliac | 49 (2.9) | 110 (4.6) | |
| First graft recipient artery (uni- or bi-iliac/femoral) | |||
| Common iliac | 195 (11.5) | 129 (5.4) | <0.001 |
| External iliac | 101 (6.0) | 99 (4.2) | |
| Common femoral | 1,246 (73.5) | 1,855 (78.3) | |
| Profunda | 99 (5.8) | 179 (7.6) | |
| Superficial femoral | 54 (3.2) | 108 (4.6) | |
| Second graft recipient artery (bi-iliac/femoral only) | |||
| Common iliac | 185 (10.9) | 113 (4.8) | <0.001 |
| External iliac | 98 (5.8) | 88 (3.7) | |
| Common femoral | 1,108 (65.5) | 1,575 (66.6) | |
| Profunda | 73 (4.3) | 149 (6.3) | |
| Superficial femoral | 43 (2.5) | 87 (3.7) | |
| First graft type | |||
| Dacron | 1,254 (74.3) | 1,793 (75.9) | 0.65 |
| Polytetrafluoroethylene | 422 (25.0) | 550 (23.3) | |
| Discharged on aspirin | 1,424 (84.7) | 2,078 (88.3) | 0.001 |
| Discharged on P2Y12 inhibitor | 445 (26.5) | 601 (25.5) | 0.50 |
| Discharged on anticoagulant | 147 (8.8) | 258 (11.0) | 0.021 |
| Discharged on statin | 1,351 (80.4) | 1,934 (82.2) | 0.14 |
| Concomitant peripheral endovascular intervention | 33 (1.9) | 62 (2.6) | 0.16 |
| Peri-operative Outcomes | |||
| Post-operative length of stay – d | 7.3 ± 5.1 | 7.1 ± 5.9 | 0.41 |
| 30-day mortality | 38 (2.2) | 34 (1.4) | 0.054 |
| Wound complication | 46 (2.7) | 82 (3.5) | 0.18 |
| Decrease in renal function | 147 (8.7) | 262 (11.1) | 0.013 |
| Return to operating room | 115 (6.8) | 144 (6.1) | 0.36 |
| Pulmonary complications | 130 (7.7) | 163 (6.9) | 0.33 |
| Cardiac complications | 147 (8.7) | 245 (10.4) | 0.078 |
Data are presented as n (%) or mean ± standard deviation.
Peri-Operative Outcomes
For PVI, female patients had higher rates of periprocedural complications with more access site hematomas (3.6% vs. 2.3%, P < 0.001) and access stenosis/occlusion (0.3% vs. 0.2%, P = 0.001). For IIB, female patients had longer LOS, but there were no differences in peri-operative complications or morbidity. There were no differences in SIB perioperative outcomes (Tables III–V).
Discharge medication differed for female compared to male patients, as they were less often prescribed aspirin for PVI (81.2% vs. 83.7%), IIB (82.7% vs. 86.6%), and SIB (84.7% vs. 88.3%) (all P < 0.05). Female patients were also less often prescribed statins on discharge after PVI (76.2% vs. 80.8%), and IIB (78.1% vs. 82.1%) (all P < 0.05) (Tables III–V).
One-Year Outcomes
Kaplan-Meier analysis at 1 year for PVI showed that female sex was associated with lower reintervention-free survival compared to male sex (84.4% ± 0.3% vs. 86.3% ± 0.2%, P < 0.001), but with similar amputation-free survival (93.4% ± 0.2% vs. 93.4% ± 0.2%, P = 0.79) and overall survival (96.4% ± 0.1% vs. 96.6% ± 0.1%, P = 0.17). Kaplan-Meier analysis at 1 year for IIB demonstrated that female compared to male sex was associated with lower reintervention-free survival (79% ± 0.9% vs. 81.2% ± 0.6%, P = 0.04), but with similar amputation-free survival (92.8% ± 0.6% vs. 93.5% ± 0.4%, P = 0.34) and survival (96.2% ± 0.4% vs. 96.4% ± 0.2%, P = 0.69). Kaplan-Meier analysis at 1 year for SIB showed that female compared to male sex was associated with lower reintervention-free survival (89.4% ± 0.9% vs. 92.6% ± 0.7%, P = 0.005), but with similar amputation-free survival (93.5% ± 0.7% vs. 94.8% ± 0.6%, P = 0.17) and survival (95.5% ± 0.5% vs. 96.6% ± 0.4%, P = 0.09).
Among patients with ambulatory function assessed at 1 year (n = 8,616 for PVI; n = 1,505 for IIB; n = 539 for SIB), female patients were less often ambulatory without assistance after PVI (89.0% vs. 92.3%, P < 0.001), but were similarly ambulatory without assistance after IIB (86.4% vs. 89.8%, P = 0.08) and SIB (94.4% vs. 95.9%, P = 0.68).
On sub-analysis of reinterventions, reinterventions after PVI were 20.7% open operations and 79.3% endovascular-only interventions. After IIB, reinterventions were 43.2% open operations and 56.8% endovascular-only interventions. After SIB, reintervention were 75.9% open operations and 24.1% endovascular-only interventions. There were no differences in the type of reintervention after PVI, IIB, or SIB by sex.
Multivariable analysis showed that female sex was associated with reinterventions for PVI (HR 1.16, 95% CI 1.09–1.24, P < 0.001), IIB, (HR 1.16, 95% CI 1.03–1.31, P = 0.016), and SIB (HR 1.6, 95% CI 1.2–2.13, P = 0.001) (Table VI; see Table S1 for full multivariable models). Sex was not associated with amputation or death after any intervention (Tables S2 and S3).
Table VI.
Multivariable-adjusted association of female sex with 1-year reintervention/death by index intervention
| Characteristic | Adjusted HR | 95% CI | P |
|---|---|---|---|
|
| |||
| Peripheral endovascular intervention | |||
| Female versus male sex | 1.16 | 1.09–1.24 | <0.001 |
| Infrainguinal bypass | |||
| Female versus male sex | 1.16 | 1.03–1.31 | 0.016 |
| Suprainguinal bypass | |||
| Female versus male sex | 1.60 | 1.20–2.13 | 0.001 |
See Table S1 for full multivariable models.
HR, hazard ratio; CI, confidence interval.
DISCUSSION
Female sex was independently associated with more reinterventions at 1 year after PVI, IIB, and SIB for IC. Worse outcomes among female patients did not extend to postoperative amputation or mortality, which had an overall low incidence in our study. Guideline-directed medical therapy, including aspirin and statin use, was less frequent among female compared with male patients in both the pre-operative and postoperative settings, though the difference was small. Medical optimization, particularly for an elective procedure, is essential and an area for immediate improvement; however, this is only 1 factor that may ameliorate the disparity in reintervention rates by patient sex. Future prospective analysis is warranted to assess the reasons for the type of intervention offered, as well as for suboptimal medical therapy, treatment failures, and need for reintervention among female patients.
The association of sex with outcomes of interventions for PAD has previously been studied. An analysis of the Nationwide Inpatient Sample from 1998 to 2009 examined sex disparities in a PAD population, consisting primarily of CLTI patients.16 Female patients were more likely to be older, have CLTI, receive endovascular procedures, and experience peri-operative complications, including mortality, compared to male patients.16 We observed more peri-operative access site complications after PVI among female patients in our analysis of IC patients, but did not find differences in mortality. However, IC patients may have fewer comorbidities contributing to mortality risk. An analysis of the United States Renal Data System from 2006 to 2011 examined differences in outcomes by sex among hemodialysis patients after lower extremity bypass.13 The indication for intervention was CLTI in nearly, 75%. Similar to our findings, more autologous conduit was used among male patients compared to female patients. Female patients more often had acute graft failure, but there were no differences by sex for long-term patency, limb salvage, or survival.13 An analysis of insurance claims in Germany for endovascular interventions to treat PAD demonstrated that female sex was associated with a higher prevalence of cardiovascular event-free survival, amputation-free survival, and overall survival.14 A VQI analysis of PVI for all types of PAD from 2010 to 2016 found that female sex was associated with higher rates of occlusion and reintervention, particularly after iliac and femoropopliteal interventions.15 Our analysis is unique given that it focuses on outcomes of interventions performed for IC. Similar to the prior studies of CLTI, women had worse peri-operative and 1-year outcomes than men.
For all patients with IC, the SVS and ESC/ESVS treatment guidelines advise antiplatelet and statin therapy (SVS: Grade 1, Level A; ESC/ESVS: Class 1, Level A for statins and Level C for antiplatelets), which have been associated with increased patency and decreased symptom recurrence after bypass for IC.1,18 Our study demonstrated that female compared to male patients less often received guideline-directed medical therapy pre-operatively and postoperatively with aspirin and statins, though the difference was small. Sex-related disparity in medical optimization has similarly been observed among female patients undergoing carotid endarterectomy in VQI centers, as well as among patients with CAD in general.9,19 A single-center study of patients with CAD treated in the outpatient setting (49.7% female) demonstrated that despite no difference in adverse drug reactions between female and male patients, female patients were less likely to be treated with aspirin, statins, and beta-blockers.19 A single-center study of newly diagnosed PAD inpatients (41% female) demonstrated that the majority of patients discharged without a statin prescription were female (67%).20 Analysis of patients undergoing PVI for PAD in the Vascular Study Group of New England (37.2% female) found that female patients were independently less likely to be prescribed Class 1 guideline-direct medical therapy with antiplatelets and statins at discharge.21 The sex-related disparity in medical optimization of female patients with cardiovascular disease may partially relate to provider perception of male patients as having a higher risk of cardiovascular events compared to female patients.22 Given that the difference in aspirin and statin use by patient sex was small, poorer medical optimization may only be 1 of multiple factors contributing to higher reintervention among female patients.
Long-term amputation free-survival rates after IC interventions were similar by patient sex. Our finding is consistent with previous met-analysis demonstrating no significant difference in long-term limb salvage after open and endovascular operations for both IC and CLTI between men and women.23 Additionally, as found in previous VQI analysis of patients receiving IC interventions, regardless of patient sex, 1-year amputation rates among patients with IC in our study were similarly higher than the expected 1–2% per annum with medical management alone.2 Therefore, surgeons should attempt an adequate period of medical therapy before offering invasive interventions.
Our study has several limitations. It is a retrospective review of prospectively collected data. Specific anatomical details were also unavailable. Surgeon bias for the type of intervention could not be accounted for. Furthermore, we could not evaluate outcomes by sex among patients with IC treated conservatively as the VQI only includes patients receiving interventions.
CONCLUSIONS
Among patients undergoing interventions for IC, female sex was associated with slightly less optimal pre-operative and postoperative medical therapy as well as more reinterventions after PVI, IIB and SIB. Peri-operative medical optimization before intervention and the durability of interventions for IC should be discussed with female patients. Further prospective investigation is warranted to better assess reasons for these sex-related health disparities.
Supplementary Material
Table IV.
Procedural details and peri-operative outcomes of infrainguinal bypass for intermittent claudication
| Characteristic | Female sex (n = 2,789) | Male sex (n = 6,525) | P |
|---|---|---|---|
|
| |||
| Procedure | |||
| Graft origin artery | |||
| External iliac | 98 (3.5) | 246 (3.8) | <0.001 |
| Common femoral | 2,246 (80.9) | 4,970 (76.5) | |
| Profunda | 61 (2.2) | 117 (1.8) | |
| Superficial femoral | 259 (9.3) | 879 (13.5) | |
| Above knee popliteal | 76 (2.7) | 208 (3.2) | |
| Below Knee Popliteal | 30 (1.1) | 76 (1.2) | |
| Tibial | 5 (0.2) | 4 (0.1) | |
| Graft recipient artery | |||
| Common femoral | 166 (6.0) | 286 (4.4) | <0.001 |
| Superficial femoral | 82 (3.0) | 153 (2.4) | |
| Profunda | 41 (1.5) | 157 (2.4) | |
| Above knee popliteal | 1,237 (44.6) | 2,369 (36.4) | |
| Below Knee Popliteal | 860 (31.0) | 2,172 (33.4) | |
| Tibial | 389 (14.0) | 1,369 (21.0) | |
| Graft type | |||
| Great saphenous vein | 1,201 (43.5) | 3,352 (51.8) | <0.001 |
| Other vein | 83 (3.0) | 255 (3.9) | |
| Prosthetic | 1,476 (53.5) | 2,865 (44.3) | |
| Discharged on aspirin | 2,304 (82.7) | 5,639 (86.6) | <0.001 |
| Discharged on P2Y12 inhibitor | 1,456 (52.3) | 3,245 (49.9) | 0.034 |
| Discharged on anticoagulant | 495 (17.8) | 1,237 (19.0) | 0.16 |
| Discharged on statin | 2,176 (78.1) | 5,344 (82.1) | <0.001 |
| Concomitant peripheral endovascular intervention | 206 (7.4) | 510 (7.8) | 0.49 |
| Concomitant endarterectomy | 836 (30.1) | 2,154 (33.1) | 0.010 |
| Peri-operative Outcomes | |||
| Post-operative length of stay – d | 4.1 ± 3.4 | 3.6 ± 3.1 | <0.001 |
| 30-day mortality | 16 (0.6) | 33 (0.5) | 0.68 |
| Wound complication | 58 (2.1) | 127 (1.9) | 0.68 |
| Decrease in renal function | 57 (2.0) | 165 (2.5) | 0.16 |
| Return to the operating room | 122 (4.4) | 264 (4.1) | 0.47 |
| Pulmonary complication | 25 (0.9) | 57 (0.9) | 0.91 |
| Cardiac complication | 88 (3.2) | 246 (3.8) | 0.14 |
Data are presented as n (%) or mean ± standard deviation.
Footnotes
SUPPLEMENTARY DATA
Supplementary data to this article can be found online at https://doi.org/10.1016/j.avsg.2022.05.036.
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