TableⅠ. Baseline Characteristics of the Patients.*
Variable
|
With Afib
|
No Afiib
|
P
|
Median age (IQR) - yr
Female sex-no. (%)
Median body-mass index(IQR)†
Diabetes-no. (%)
Heart rate at baseline(IQR)-beats per minute
Systolic BP at baseline(IQR)-mm Hg
Diastolic BP at baseline(IQR)-mm Hg
Smoking-no. (%)
Current
Former
Never
Alcohol use-no. (%)
Never
Rarely
Currently consumes
Baseline CrCl mg/dL-no. (%)
≤50
>50 and <80
≥80
>95
Relevant disease history-no. (%)
Hypertension
Cardiovascular disease‡
Carotid artery disease
Ischemic stroke
hyperlipidemia
Cholesterol, mmol/L-no. (%)
HDL cholesterol, mmol/L-no. (%)
LDL cholesterol, mmol/L-no. (%)
Rutherford category-no. (%)
2
3
4
5
Rutherford category(IV~V)-no. (%)
Runoff vessels (<50% stenosis)-no. (%)
0
1
2
Runoff vessels-no. (%)
Yes
No
CHADSVASC score-no. (%)
1
≥2
Lesion location-no. (%)§
Limited to Infrapopliteal artery
Entire lower extremity arterial
Lesion length, cm-no. (%)
Total
Infrapopliteal arterial lesion
Lesion severity-no. (%)
Stenosis
Occlusion
Preoperative ABI-(IQR)
Postoperative ABI-(IQR)
Stent placement in suprapopliteal artery-no. (%)
Bare metal
Drug-eluting
Balloon placement in Infrapopliteal artery-no. (%)
Bare
Drug-coated
Residual stenosis(IQR)
History of vascular angioplasty-no. (%)
Mdicine-no. (%)
Statin
ACE inhibitor or ARB
Aspirin
Cilostazol
Clopidogrel
Rivaroxaban
|
77(68,81)
20(23.8)
25.3(22.6,26.4)
36(42.9)
85(77,89)
133(127,142)
86(78,99.8)
55(65.5)
9(10.7)
20(23.8)
41(48.8)
18(21.4)
25(29.8)
10(11.9)
23(27.4)
51(60.7)
15(17.9)
56(66.7)
22(26.2)
24(28.6)
7(8.3)
57(67.9)
4.3(3.6,4.9)
1.3(0.6,1.7)
2.5(1.9,3.2)
1(1.2)
47(56.0)
21(25.0)
15(17.9)
47(56.0)
9(10.7)
45(53.6)
30(35.7)
75(89.3)
9(10.7)
14(16.7)
70(83.3)
37(44.0)
47(56.0)
27.3(11.7,33.5)
11.6(9.7,12.7)
30(35.7)
54(64.3)
0.28(0.23,0.35)
0.76(0.70,0.83)
25(29.8)
17(20.2)
26(31.0)
58(69.0)
13(11,16)
18(22.2)
53(63.1)
52(61.9)
44(52.4)
42(50.0)
49(58.3)
49(58.3)
|
76(69,81)
29(31.5)
25.4(22.3,26.7)
48(52.2)
80(76,88)
134(127,142)
89(78.99)
48(52.2)
10(10.9)
34(37.0)
51(55.4)
12(13.0)
29(31.5)
4(4.4)
36(39.1)
52(56.5)
18(19.6)
56(60.9)
27(29.3)
31(33.7)
5(5.4)
59(64.1)
4.3(3.8,5.0)
1.4(0.8,1.7)
2.5(1.8,3.2)
0(0)
44(47.8)
24(26.1)
24(26.1)
45(48.9)
12(13.0)
59(64.1)
21(22.8)
80(87.0)
12(13.0)
26(28.2)
66(71.8)
53(57.6)
39(42.4)
22.4(12.6,31.8)
11.7(10.5,12.8)
33(35.9)
59(64.1)
0.30(0.21,0.35)
0.77(0.73,0.83)
17(18.5)
22(23.9)
28(32.2)
59(67.8)
13(9,15)
17(18.5)
54(58.7)
48(52.2)
42(45.7)
37(40.2)
54(58.7)
55(59.8)
|
0.85
0.25
0.48
0.22
0.08
0.62
0.45
0.15
0.33
0.16
0.43
0.64
0.46
0.45
0.34
0.34
0.38
0.96
0.39
0.35
0.17
0.63
0.06
0.07
0.58
0.23
0.98
0.99
0.28
0.21
0.86
0.28
0.54
0.55
0.19
0.37
0.19
0.96
0.85
|
*There were no significant differences between groups. Percentages may not total 100 because of rounding. Continuous data are presented as the means ± standard deviation(if it matches normal distribution) or Median(interquartile range)(if it matches skewed distribution).; categorical data are given as the counts (percentage). Percentages were based on the number of subjects in the column heading as the denominator unless specified otherwise. Abbreviations: ACE denotes angiotensin-converting enzyme;ARB angiotensin-receptor blocker, ABI, ankle-brachial index;CrCl, creatinine clearance; HDL, high-density lipoprotein; LDL, low-density cholesterol;IQR denotes interquartile range.
†The body-mass index is the weight in kilograms divided by the square of the height in meters.
‡Cardiovascular diseaseis is defined as myocardial infarction, percutaneous coronary intervention, or coronaryartery bypass grafting (CABG).
§The term "Limited to infrapopliteal artery" encompasses arterial stenosis or occlusion that results in interrupted distal limb blood flow, requiring endovascular therapy (EVT). Under this condition, suprapopliteal artery disease typically presents with stenosis degrees below 50% and does not require EVT. The term "Entire lower extremity arterial" denotes the pathological condition in which surgical interventions have been performed on both the suprainguinal and infrapopliteal arteries due to stenosis or occlusion.
TableⅡ. Efficacy Outcomes.*
outcome
|
AF
(N=84)
Event No.(%)
|
Events/100 patient-yr
|
No AF
(N=92)
Event No. (%)
|
Events/100 patient-yr
|
HR (95%CI)
|
P Value
|
Primary efficacy outcome: increase in Rutherford classification by at least 1 grade over post-angioplasty, target lesion revascularization, acute limb ischemia, amputation for vascular reasons
Increase in Rutherford classification by at least 1 grade over post-angioplasty
Target lesion revascularization
Acute limb ischemia
Amputation for vascular reasons
Secondary efficacy outcome: increase in Rutherford classification by at least 1 grade over post-angioplasty, target lesion revascularization, acute limb ischemia, amputation for vascular reasons , myocardial infarction, ischemic stroke, death from cardiovascular causes, all-cause death
Cardiovascular and cerebrovascular major adverse events: myocardial infarction, ischemic stroke, death from cardiovascular causes
Primary efficacy outcome in patients with isolated infrapopliteal disease
Secondary efficacy outcome in patients with isolated infrapopliteal disease
Cardiovascular and cerebrovascular major adverse events in patients with isolated infrapopliteal disease
|
59(70.2)
49(58.3)
57(67.9)
22(26.2)
22(26.2)
64(76.2)
26(31.0)
25(67.6)
28(75.7)
15(40.5)
|
119.031
83.017
112.344
31.218
31.782
152.570
38.205
115.244
161.658
51.802
|
55(59.8)
44(47.8)
51(55.4)
16(17.4)
16(17.4)
60(65.2)
14(15.2)
26(49.1)
30(56.6)
8(15.1)
|
82.982
59.736
77.048
19.329
18.862
94.584
15.217
64.065
77.249
16.193
|
1.434 (0.993, 2.071)
1.390 (0.923, 2.092)
1.458(1.001,2.123)
1.615(0.848,3.075)
1.685(0.890,3.189)
1.613(1.134,2.294)
2.305(1.204,4.415)
1.799(1.039,3.115)
2.093(1.250,3.503)
3.199(1.356,7.546)
|
0.027
0.068
0.024
0.137
0.092
0.001
0.010
0.024
0.001
0.006
|
*Event rates are provided for the adjudicated events that include the primary efficacy outcomes, secondary efficacy outcomes, and their respective components. CI denotes confidence interval.
TableⅢ.Variables associated with study outcomes in patients with infrapopliteal artery disease in cox regression analyses
Variable
|
Crude HR
|
95% CI
|
P
|
Adjusted HR
|
95%CI
|
P
|
Primary efficacy outcome at one-year*
|
Atrial fibrillation
Median age
Female sex
Median body-mass index
Diabetes
Heart rate at baseline (beats per minute)
Systolic BP at baseline (mm Hg)
Diastolic BP at baseline (mm Hg)
Smoking
Alcohol use
Baseline CrCl, mg/dL
Hypertension
Cardiovascular disease
Carotid artery disease
Ischemic stroke
hyperlipidemia
Rutherford category(IV~V)
CHADSVASC score(≥2)
Popliteal artery disease extending proximally
Lesion length, cm
Total
suprapopliteal arterial lesion
Infrapopliteal arterial lesion
Lesion severity(stenosis or occlusion )
Balloon placement in Infrapopliteal artery
Residual stenosis
History of vascular angioplasty
Runoff vessels(Yes or No)
Rivaroxaban
|
1.513
1.007
1.017
1.015
1.276
1.022
1.001
1.005
1.034
1.178
1.045
1.104
1,316
1.069
1.174
1.197
1.498
1.392
1.492
1.023
1.014
1.220
1.575
0.615
1.045
0.988
2.174
1.081
|
1.047-2.186
0.998-1.027
0.825-1.247
0.970-1.063
0.884-1.843
1.003-1.042
0.990-1.012
0.993-1.018
0.847-1.262
0.816-1.702
0.996-1.095
0.751-1.622
0.883-1.959
0.873-1.309
0.594-2.320
0.808-1.773
1.036-2.165
0.809-2.396
1.031-2.159
1.006-1.040
0.998-1.031
1.108-1.344
1.061-2.340
0.418-0.904
0.996-1.095
0.789-1.237
1.277-3.700
0.744-1.572
|
0.028
0.461
0.893
0.510
0.194
0.022
0.828
0.396
0.743
0.382
0.070
0.614
0.177
0.518
0.645
0.269
0.032
0.233
0.033
0.009
0.096
<0.001
0.024
0.013
0.066
0.915
0.004
0.683
|
1.729
1.291
1.425
1.239
1.448
0.585
1.061
2.056
|
1.155-2.588
0.870-1.916
0.951-2.135
1.119-1.371
0.965-2.173
0.387-0.883
1.009-1.115
1.165-3.628
|
0.008
0.205
0.086
<0.001
0.074
0.011
0.021
0.013
|
Secondary efficacy outcome at one-year*
|
|
|
|
Atrial fibrillation
Median age
Female sex
Median body-mass index
Diabetes
Heart rate at baseline (beats per minute)
Systolic BP at baseline (mm Hg)
Diastolic BP at baseline (mm Hg)
Smoking
Alcohol use
Baseline CrCl, mg/dL
Hypertension
Cardiovascular disease
Carotid artery disease
Ischemic stroke
hyperlipidemia
Rutherford category(IV~V)
CHADSVASC score(≥2)
Popliteal artery disease extending proximally
Lesion length, cm
Total
suprapopliteal arterial lesion
Infrapopliteal arterial lesion
Lesion severity(stenosis or occlusion )
Balloon placement in Infrapopliteal artery
Residual stenosis
History of vascular angioplasty
Runoff vessels(Yes or No)
Rivaroxaban
|
1.778
1.011
1.024
0.996
1.045
1.022
0.994
0.997
1.011
1.133
1.003
1.117
1.126
1.015
1.117
1.091
1.252
1.312
1.350
1.017
1.013
1.099
1.518
0.885
1.032
0.984
1.925
1.037
|
1.247-2.535
0.992-1.030
0.840-1.247
0.954-1.040
0.735-1.487
1.004-1.040
0.984-1.005
0.985-1.010
0.836-1.224
0.796-1.613
0.993-1.012
0.771-1.617
0.764-1.659
0.694-1.483
0.566-2.201
0.750-1.586
0.880-1.782
0.786-2.189
0.948-1.992
1.001-1.034
0.997-1.029
1.009-1.198
1.038-2.220
0.606-1,292
0.986-1.080
0.790-1.225
1.152-3.219
0.724-1.486
|
0.001
0.263
0.817
0.850
0.806
0.018
0.302
0.647
0.907
0.488
0.561
0.559
0.550
0.940
0.750
0.648
0.211
0.298
0.096
0.041
0.123
0.023
0.031
0.527
0.174
0.883
0.012
0.841
|
1.912
1.139
1.204
1.109
1.430
0.780
1.035
1.959
|
1.303-2.806
0.776-1.673
0.821-1.765
1.013-1.214
0.967-2.115
0.522-1.166
0.986-1.088
1.140-3.367
|
0.001
0.506
0.342
0.025
0.074
0.226
0.165
0.015
|
Cardiovascular and cerebrovascular major adverse events*
|
Atrial fibrillation
Median age
Female sex
Median body-mass index
Diabetes
Heart rate at baseline (beats per minute)
Systolic BP at baseline (mm Hg)
Diastolic BP at baseline (mm Hg)
Smoking
Alcohol use
Baseline CrCl, mg/dL
Hypertension
Cardiovascular disease
Carotid artery disease
Ischemic stroke
hyperlipidemia
Rutherford category(IV~V)
CHADSVASC score(≥2)
Popliteal artery disease extending proximally
Lesion length, cm
Total
suprapopliteal arterial lesion
Infrapopliteal arterial lesion
Lesion severity(stenosis or occlusion )
Balloon placement in Infrapopliteal artery
Residual stenosis
History of vascular angioplasty
Runoff vessels(Yes or No)
Rivaroxaban
|
2.339
0.995
1.011
0.898
0.624
1.000
0.978
0.977
0.848
0.643
1.002
1.104
0.719
0.957
0.320
0.824
0.710
1.435
0.785
0.990
0.995
0.914
0.936
2.125
0.961
0.870
1.035
0.838
|
1.221-4.482
0.963-1.029
0.715-1.431
0.828-0.973
0.329-1.185
0.969-1.023
0.957-0.998
0.956-0.999
0.593-1.213
0.339-1.220
0.985-1.018
0.804-1.514
0.342-1.511
0.687-1.332
0.044-2.332
0.434-1.562
0.377-1.336
0.661-3.115
0.419-1.469
0.961-1.020
0.966-1.024
0.810-1.031
0.494-1.776
0.979-4.613
0.889-1.038
0.608-1.244
0.405-2.642
0.450-1.563
|
0.010
0.789
0.949
0.009
0.149
0.982
0.028
0.042
0.367
0.177
0.836
0.541
0.384
0.794
0.261
0.552
0.289
0.361
0.449
0.499
0.714
0.142
0.840
0.057
0.311
0.445
0.943
0.579
|
2.338
0.760
0.990
0.927
1.999
0.938
|
1.202-4.550
0.385-1.499
0.961-1.020
0.807-1.066
0.918-4.352
0.860-1.023
|
0.012
0.428
0.520
0.287
0.081
0.148
|
Primary efficacy outcome in isolated infrapopliteal disease sub-group at one-year*
|
Atrial fibrillation
Median age
Female sex
Median body-mass index
Diabetes
Heart rate at baseline (beats per minute)
Systolic BP at baseline (mm Hg)
Diastolic BP at baseline (mm Hg)
Smoking
Alcohol use
Baseline CrCl, mg/dL
Hypertension
Cardiovascular disease
Carotid artery disease
Ischemic stroke
hyperlipidemia
Rutherford category(IV~V)
CHADSVASC score(≥2)
Infrapopliteal arterial Lesion length, cm
Lesion severity(stenosis or occlusion )
Balloon placement in Infrapopliteal artery
Residual stenosis
History of vascular angioplasty
Runoff vessels(Yes or No)
Rivaroxaban
|
1.876
1.005
1.058
1.016
1.778
1.038
1.001
1.000
1.026
0.920
1.001
1.061
0.724
1.250
1.503
1.548
2.536
0.809
1.426
1.983
1.048
1.053
1.025
1.335
1.213
|
1.081-3.225
0.977-1.034
0.765-1.463
0.955-1.081
1.025-3.084
1.009-1.067
0.986-1.016
0.983-1.019
0.769-1.367
0.530-1.598
0.989-1.013
0.601-1.872
0.412-1.271
0.698-2.240
0.596-3.788
0.856-2.801
1.447-4.445
0.546-1.200
1.195-1.700
1.054-3.729
0.565-1.943
0.985-1.126
0.734-1.432
0.569-3.133
0.691-2.129
|
0.027
0.711
0.734
0.621
0.041
0.011
0.879
0.957
0.862
0.768
0.880
0.839
0.261
0.453
0.388
0.148
0.001
0.293
<0.001
0.026
0.881
0.124
0.884
0.506
0.501
|
4.450
1.470
2.862
1.475
1.076
2.566
|
2.303-8.599
0.804-2.686
1.530-5.357
1.216-1.788
0.996-1.162
1.013-6.501
|
<0.001
0.211
0.001
<0.001
0.063
0.047
|
*Variables included in the multivariate Cox regression analysis will display the adjusted HR values along with their corresponding 95% CI.In the preliminary univariate Cox regression analysis, we found that apart from atrial fibrillation, which evidently affects patient prognosis (whether related to adverse limb events or cardiovascular and cerebrovascular outcomes), there are several other factors with univariate Cox regression p-values less than 0.1 or that potentially influence patient outcomes. On the basis of including these variables, we constructed a multivariate Cox regression model. We calculated the variance inflation factor (VIF) for each variable to exclude multicollinearity. Finally, using the adjusted variables, we established the multivariate Cox regression model, obtaining adjusted hazard ratios (HR), 95% confidence intervals (CI), and p-values.
TableⅣ.The association between atrial fibrillation and the study outcomes in the sensitivity analyses.
The Study Outcomes
|
Hazard Ratio
|
95% CI
|
p
|
Primary efficacy outcome at one-year*
|
Model 1
Model 2
Model 3
|
1.733
1.679
1,754
|
1.158-2.593
1.116-2.526
1.175-2.618
|
0.007
0.013
0.006
|
Secondary efficacy outcome at one-year†
|
Model 1
Model 2
Model 3
|
1.932
1.890
1.874
|
1.316-2.838
1.285-2.779
1.294-2.713
|
0.001
0.001
0.001
|
Cardiovascular and cerebrovascular major adverse events at one year‡
|
Model 1
Model 2
Model 3
|
2.345
2.093
2.332
|
1.114-4.173
1.060-4.132
1.204-4.517
|
0.012
0.033
0.012
|
Primary efficacy outcome in patients with isolated infrapopliteal disease at one-year§
|
Model 1
Model 2
Model 3
|
5.226
4.476
4.705
|
2.584-10.730
2.314-8.657
2.426-9.124
|
<0.001
<0.001
<0.001
|
* Model 1 uses variables like age, gender, atrial fibrillation, Rutherford category (IV-V), and arterial conditions for a multivariate Cox regression. Model 2 expands on this, adding baseline heart rate, CrCl, and lesion length. Model 3, derived from Model 2, omits heart rate, CrCl, lesion length, and Rutherford category (IV-V).
† Model 1 uses age, gender, atrial fibrillation, Rutherford category (IV-V), and various arterial conditions for a Cox regression analysis. Model 2 adds factors like baseline heart rate and lesion length. Model 3, based on Model 2, omits heart rate, lesion length, Rutherford category (IV-V), and specific arterial conditions.
‡ Model 1 utilizes a Cox regression with variables like age, gender, atrial fibrillation, Rutherford category (IV-V), and lesion metrics. Model 2 includes atrial fibrillation, BMI, baseline BP, Rutherford category (IV-V), and other lesion parameters. Model 3 refines Model 2 by excluding BMI, baseline BP, Rutherford category (IV-V), and lesion length.
§ Model 1 uses a Cox regression with variables: age, gender, atrial fibrillation, diabetes, Rutherford category (IV-V), infrapopliteal arterial lesion, runoff vessels, and residual stenosis. Model 2 includes atrial fibrillation, baseline heart rate, diabetes, Rutherford category (IV-V), lesion length and severity, residual stenosis, and runoff vessels. Model 3 is like Model 2 but omits diabetes.
TableⅤ. subgroup analysis
Subgoup
|
AF
|
No AF
|
Hazard Ratio(95%CI)
|
P value for interaction
|
All participants
|
59/84(70.238%)
|
55/92(59.783%)
|
2.120(1.431-3.140)
|
|
age
|
|
|
|
0.458
|
<75
|
27/40(67.500%)
|
27/43(62.791%)
|
1.816(1.031-3.210)
|
|
>=75
|
32/44(72.727%)
|
28/49(57.143%)
|
2.434(1.422-4.167)
|
|
gender
|
|
|
|
0.692
|
Female
|
15 /20(75.00%)
|
16 /29(55.172%)
|
2.394(1.155-4.962)
|
|
Male
|
44 /64(68.75%)
|
39 /63(61.905%)
|
2.020(1.285-3.176)
|
|
BMI
|
|
|
|
0.385
|
<=25
|
27 /36(75.000%)
|
19/35(54.286%)
|
2.601(1.419-4.768)
|
|
>25
|
32/ 48(66.667%)
|
36 /57(63.158%)
|
1.859(1.130-3.056)
|
|
lesion_length
|
|
|
|
0.923
|
<=11
|
18 /34(52.941%)
|
9/25 (36.000%)
|
2.081(0.926-4.673)
|
|
>11
|
41/50 (82.000%)
|
46 /67(68.657%)
|
2.177(1.401-3.382)
|
|
lesion_severity
|
|
|
|
0.452
|
Narrow
|
17 /30(56.667%)
|
19/32 (59.375%)
|
1.714(0.862-3.409)
|
|
Occluded
|
42/54(77.778%)
|
36/60 (60.000%)
|
2.339(1.471-3.718)
|
|