Sex-Related Differences in the Outcomes of Endovascular Interventions for Chronic Limb-Threatening Ischemia: Results from the LIBERTY 360 Study

Figures & data

Figure 1 Kaplan–Meier estimates of freedom from major amputation during follow-up.

Figure 2 Kaplan–Meier estimates of freedom from major amputation/death during follow-up.

Table 1 Baseline Characteristics of Participants

Characteristics	Male (n=437)	Female (n=252)	P-value
Age, year	69.6 ± 10.8 (N=436)	70.5 ± 12.0 (N=252)	0.306
Race
American Indian or Alaska Native	2 (0.5%)	2 (0.8%)	0.626
Asian	2 (0.5%)	0 (0.0%)	0.535
Black or African American	59 (13.5%)	51 (20.2%)	0.023
Native Hawaiian or Other Pacific Islander	0 (0.0%)	1 (0.4%)	0.366
White	367 (84.0%)	194 (77.0%)	0.025
Other	7 (1.6%)	4 (1.6%)	1.000
BMI	29.0 ± 6.0 (N=437)	29.4 ± 7.0 (N=252)	0.404
eGFR	60.1 ± 29.0 (N=436)	57.9 ± 29.5 (N=252)	0.342
Smoking history	306 (70.0%)	133 (52.8%)	<.0001
Current smoker	72 (16.5%)	44 (17.5%)	0.752
Former smoker	234 (53.5%)	89 (35.3%)	<.0001
Diabetes	317 (72.5%)	169 (67.1%)	0.140
Hyperlipidemia	372 (85.1%)	207 (82.1%)	0.331
Hypertension	402 (92.0%)	240 (95.2%)	0.118
Renal disease	180 (41.2%)	95 (37.7%)	0.376
Among patients with renal disease, patients being on hemodialysis	44 (24.4%)	26 (27.4%)	0.663
Coronary artery disease	287 (65.7%)	142 (56.3%)	0.018
Myocardial infarction	127 (29.1%)	43 (17.1%)	0.0005
Stroke/TIA	60 (13.7%)	41 (16.3%)	0.373
Run-off vessels pre-treatment (Core lab)	N=389	N=226	0.326
3	49 (12.6%)	41 (18.1%)	0.076
2	152 (39.1%)	83 (36.7%)	0.606
1	137 (35.2%)	75 (33.2%)	0.660
0	51 (13.1%)	27 (11.9%)	0.708
Run-off vessels post-treatment (Core lab)	N=342	N=192	0.453
3	72 (21.1%)	49 (25.5%)	0.238
2	144 (42.1%)	72 (37.5%)	0.313
1	114 (33.3%)	67 (34.9%)	0.775
0	12 (3.5%)	4 (2.1%)	0.436
Previous EVT of target limb	N=437	N=252	0.778
No	305 (69.8%)	164 (65.1%)
Yes	131 (30.0%)	88 (34.9%)
Unknown	1 (0.2%)	0 (0.0%)
Previous bypass surgery of target limb	N=437	N=252	0.399
No	416 (95.2%)	244 (96.8%)
Yes	20 (4.6%)	8 (3.2%)
Unknown	1 (0.2%)	0 (0.0%)
Prior stent placed, target limb	N=437	N=252	0.770
No	374 (85.6%)	216 (85.7%)
Yes	62 (14.2%)	36 (14.3%)
Unknown	1 (0.2%)	0 (0.0%)
Previous amputations of target limb	N=437	N=252	0.209
Target limb	33 (7.6%)	19 (7.5%)	1.000
Non-target limb	48 (11.0%)	19 (7.5%)	0.181
Both limbs	20 (4.6%)	6 (2.4%)	0.212
None	336 (76.9%)	208 (82.5%)	0.082
If previous amputations, target limb	N=53	N=25	0.698
Above knee	0 (0.0%)	0 (0.0%)	–
Below knee/above ankle	0 (0.0%)	0 (0.0%)	–
Toe(s) only	50 (94.3%)	25 (100.0%)	0.547
Foot only	4 (7.5%)	0 (0.0%)	0.300
Antiplatelet therapy at discharge	405 (92.7%)	232 (92.1%)	0.767
Aspirin	345 (78.9%)	204 (81.0%)	0.557
Clopidogrel	313 (71.6%)	196 (77.8%)	0.087
Dual	284 (65.0%)	186 (73.8%)	0.018
Anti-coagulants at discharge	49 (11.2%)	29 (11.5%)	0.901
Warfarin	33 (7.6%)	18 (7.1%)	0.881
Other	16 (3.7%)	12 (4.8%)	0.549
Anti-hyperlipidemic at discharge	351 (80.3%)	185 (73.4%)	0.037
Anti-hypertensive at discharge	388 (88.8%)	229 (90.9%)	0.439
Hospitalization	222 (50.8%)	143 (56.7%)	0.133
Among patients hospitalized, ICU admissions	N=222	N=143	1.000
No	198 (89.2%)	127 (88.8%)
Yes	24 (10.8%)	16 (11.2%)
Time of admission to discharge, hours	44.2 ± 104.2 (N=435)	40.1 ± 83.5 (N=252)	0.597

Abbreviations: N, number of patients; BMI, body mass index; eGFR, estimated glomerular filtration rate; TIA, transient ischemic attack; EVT, endovascular therapy; ICU, intensive care unit.

Table 2 Lesion Characteristics

Characteristics	Male (N=596)	Female (N=327)	P-value
Lesion location within the leg (summarized)	N=596	N=327	0.028
ATK Only	142 (23.8%)	105 (32.1%)	0.008
BTK Only	375 (62.9%)	178 (54.4%)	0.014
Unknown	1 (0.2%)	1 (0.3%)	1.0000
Lesion location within the leg	N=596	N=327	0.025
SFA Only	15 (2.5%)	14 (4.3%)	0.167
SFA to popliteal	51 (8.6%)	48 (14.7%)	0.005
Popliteal only	76 (12.8%)	43 (13.1%)	0.918
ATK and BTK	78 (13.1%)	43 (13.1%)	1.000
SFA to BTK	16 (2.7%)	13 (4.0%)	0.325
Popliteal to BTK	62 (10.4%)	30 (9.2%)	0.646
BTK Only	375 (62.9%)	178 (54.4%)	0.014
Unknown	1 (0.2%)	1 (0.3%)	1.000
Mean target lesion length, mm	127.4 ± 113.3 (N=559)	126.9 ± 117.3 (N=305)	0.950
Target lesion length (mm)	N=559	N=305	0.929
<40	152 (27.2%)	83 (27.2%)	1.000
40–99	141 (25.2%)	80 (26.2%)	0.745
≥100	266 (47.6%)	142 (46.6%)	0.776
Mean distal RVD, mm	3.2 ± 1.3 (N=574)	3.0 ± 1.0 (N=311)	0.013
Mean preprocedural MLD, mm	0.6 ± 0.8 (N=579)	0.6 ± 0.8 (N=315)	0.856
Mean preprocedural stenosis, %	83.4 ± 19.6 (N=582)	81.8 ± 20.0 (N=316)	0.247
Chronic total occlusion of the lesion	260/582 (44.7%)	128/316 (40.5%)	0.232
TASC lesion type	N=575	N=311	0.742
A	272 (47.3%)	144 (46.3%)	0.778
B	101 (17.6%)	62 (19.9%)	0.414
C	103 (17.9%)	58 (18.6%)	0.785
D	99 (17.2%)	47 (15.1%)	0.449
Predominantly calcified plaque	341/553 (61.7%)	155/305 (50.8%)	0.002
PARC stenosis	N=582	N=316	0.654
Mild	38 (6.5%)	22 (7.0%)	0.782
Moderate	106 (18.2%)	65 (20.6%)	0.423
Severe	178 (30.6%)	101 (32.0%)	0.706
Occluded	260 (44.7%)	128 (40.5%)	0.232
Target lesion access site	N=648	N=362	0.242
Femoral	597 (92.1%)	348 (96.1%)	0.016
Popliteal	3 (0.5%)	2 (0.6%)	1.000
Tibial	50 (7.7%)	18 (5.0%)	0.116
Pedal	41 (6.3%)	17 (4.7%)	0.325
Toe	0 (0.0%)	0 (0.0%)	-
Brachial	1 (0.2%)	0 (0.0%)	1.000
Approach	N=648	N=362	0.572
Ipsilateral	171 (26.4%)	85 (23.5%)	0.327
Contralateral	429 (66.2%)	251 (69.3%)	0.328
Dual access	48 (7.4%)	26 (7.2%)	1.000
Access site position relative to lesion	N=648	N=362	0.614
Anterograde	554 (85.5%)	316 (87.3%)	0.449
Retrograde	46 (7.1%)	20 (5.5%)	0.356
Dual access	48 (7.4%)	26 (7.2%)	1.000
Mean postprocedural MLD, mm	2.3 ± 1.3 (N=560)	2.3 ± 1.1 (N=305)	0.967
Mean acute MLD gain	1.7 ± 1.1 (N=553)	1.7 ± 1.1 (N=302)	0.931
Mean postprocedural stenosis, %	35.2 ± 21.6 (N=560)	32.0 ± 20.4 (N=306)	0.034

Abbreviations: ATK, above the knee; SFA, superficial femoral; BTK, below the knee; RVD, reference vessel diameter; MLD, minimal lumen diameter; TASC, Trans-Atlantic Inter-Society Consensus Document; PARC, Consensus Definitions from Peripheral Academic Research Consortium; N, number of lesions.

Table 3 Procedure Characteristics and Target Lesion Device Use

Characteristics	Male (N=437)	Female (N=252)	P-value
Mean procedure time, minutes	84.9 ± 47.4 (N=437)	77.8 ± 41.3 (N=251)	0.049
Mean fluoroscopy time, minutes	28.1 ± 19.4 (N=434)	24.2 ± 15.3 (N=250)	0.006
Mean Contrast volume, mL	166.4 ± 98.3 (N=436)	165.4 ± 81.3 (N=250)	0.898
Inflow vessel disease (>50% stenosis)	151 (34.6%)	95 (37.7%)	0.410
Inflow treatment performed, target limb	N=296	N=178	0.658
No	227 (76.7%)	133 (74.7%)
Yes	69 (23.3%)	45 (25.3%)
Target lesions treated per subject (Core lab)	1.4 ± 0.6 (N=436)	1.3 ± 0.6 (N=251)	0.213
Mean number of devices used per subject (atherectomy, balloon, stent)	3.5 ± 2.1 (N=437)	3.3 ± 2.0 (N=252)	0.151
Device information available from site (Core lab)	N=596	N=327	0.280
No	12 (2.0%)	3 (0.9%)
Yes	584 (98.0%)	324 (99.1%)
Lesions treated with balloons	562/584 (96.2%)	319/324 (98.5%)	0.067
POBA	475 (81.3%)	256 (79.0%)	0.431
DCB	40 (6.8%)	25 (7.7%)	0.687
Cutting	48 (8.2%)	36 (11.1%)	0.153
Focal Force	83(14.2%)	45 (13.9%)	0.921
Scoring	8 (1.4%)	3 (0.9%)	0.755
Mean maximum nominal balloon diameter, mm	3.8 ± 1.4 (N=562)	3.8 ± 1.3 (N=319)	0.755
Mean maximum balloon length, mm	139.1 ± 114.1 (N=562)	136.7 ± 77.3 (N=319)	0.743
Bail out stenting	25/584 (4.3%)	9/324 (2.8%)	0.280
Lesions treated with atherectomy	383/584 (65.6%)	219/324 (67.6%)	0.558
Diamondback	283 (48.5%)	152 (46.9%)	0.678
Jetstream	6 (1.0%)	7 (2.2%)	0.242
Laser	37 (6.3%)	18 (5.6%)	0.667
Rotablator	5 (0.9%)	2 (0.6%)	1.000
Turbohawk/Silverhawk/HawkOne	50 (8.6%)	37 (11.4%)	0.195
Phoenix	9 (1.5%)	5 (1.5%)	1.000
Bard Crosser	3 (0.5%)	5 (1.5%)	0.142
Lesions treated with stent	86/584 (14.7%)	50/324 (15.4%)	0.772
DES	34 (5.8%)	15 (4.6%)	0.540
BMS	53 (9.1%)	35 (10.8%)	0.414
Covered	5 (0.9%)	1 (0.3%)	0.430
Mean maximum stent diameter, mm	5.1 ± 1.4 (N=86)	5.2 ± 1.3 (N=50)	0.818
Mean maximum stent length, mm	81.3 ± 48.5 (N=86)	86.3 ± 43.1 (N=50)	0.550

Abbreviations: POBA, plain balloon angioplasty; DCB, drug-coated balloon; DES, drug-eluting stents; BMS, bare metal stents; N, number of patients.

Table 4 Periprocedural Complications and Short-Term Outcomes (in-Hospital)

Characteristics	Male	Female	P-value
Procedural success (<50% residual stenosis, without significant angiographic complications)	297/403 (73.7%)	179/234 (76.5%)	0.451
Lesion success (<50% residual stenosis, without significant angiographic complications)	443/566 (78.3%)	243/307 (78.9%)	0.864
Abrupt closure	14/594 (2.4%)	2/327 (0.6%)	0.022
Severe angiographic complications	58/591 (9.8%)	38/324 (11.7%)	0.485
Severe dissection (Type C-F)	20/594 (3.4%)	5/327 (1.5%)	0.083
Perforation	9/594 (1.5%)	7/327 (2.1%)	0.508
Distal embolization	25/591 (4.2%)	24/324 (7.4%)	0.106
In-hospital MAE	3/422 (0.7%)	6/247 (2.4%)	0.083
In-hospital death	0/422 (0.0%)	3/247 (1.2%)	0.049
In-hospital major amputation	2/422 (0.5%)	2/247 (0.8%)	0.623
In-hospital TVR	1/422 (0.2%)	1/247 (0.4%)	1.000

Abbreviations: MAE, major adverse event; TVR, target vessel revascularization.

Table 5 Hazard Ratios (HR) and 95% Confidence Intervals of Outcomes During Follow-Up (Male Vs Female)

Outcomes	HR 95% CI	P-value
1-month
MAE	1.40 [0.65, 3.05]	0.391
Death	0.57 [0.12, 2.83]	0.493
Major amputation	1.53 [0.40, 5.75]	0.532
TVR	2.68 [0.77, 9.32]	0.121
Major amputation/death	0.95 [0.35, 2.63]	0.928
6-month
MAE	1.23 [0.84, 1.80]	0.299
Death	1.35 [0.69, 2.66]	0.380
Major amputation	1.83 [0.78, 4.29]	0.162
TVR	1.26 [0.82, 1.93]	0.293
Major amputation/death	1.42 [0.83, 2.42]	0.199
12-month
MAE	1.13 [0.83, 1.54]	0.450
Death	1.18 [0.70, 1.98]	0.546
Major amputation	2.13 [0.98, 4.67]	0.058
TVR	1.09 [0.78, 1.52]	0.627
Major amputation/death	1.35 [0.87, 2.09]	0.175
18-month
MAE	1.10 [0.82, 1.46]	0.537
Death	1.37 [0.85, 2.22]	0.192
Major amputation	2.36 [1.09, 5.12]	0.030
TVR	1.05 [0.77, 1.43]	0.771
Major amputation/death	1.53 [1.02, 2.30]	0.042
24-month
MAE	1.15 [0.87, 1.53]	0.326
Death	1.35 [0.87, 2.09]	0.178
Major amputation	2.02 [1.00, 4.08]	0.051
TVR	1.10 [0.81, 1.49]	0.527
Major amputation/death	1.43 [0.98, 2.08]	0.060
36-month
MAE	1.19 [0.90, 1.56]	0.224
Death	1.24 [0.85, 1.80]	0.260
Major amputation	1.69 [0.87, 3.26]	0.119
TVR	1.13 [0.84, 1.51]	0.426
Major amputation/death	1.29 [0.93, 1.79]	0.133

Abbreviations: MAE, major adverse event; TVR, target vessel revascularization; HR, hazard ratio; CI, confidence interval.