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Supplemental results section
Landmark analysis
During the first 30 days post-TAVR, 23 patients died and 10 patients underwent changes to their
anti-thrombotic therapy. Therefore, the landmark analysis of the events occurred after the first 30
days, comprising 588 patients, 95 patients (116 person-years) in MT group and 493 (471 personyears) in MAT group. One hundred patients died [19 patients (16.3% person-years) in MT vs. 81
(16.4% person-years) in MAT group; adjusted-HR (95%-CI) 1.03 (0.62-1.72), p=0.91], 50 due to
cardiovascular reason [7 patients (6.0% person-years) in MT vs. 43 (9.13% person-years) in
MAT group; adjusted-HR (95%-CI) 1.42 (0.63-3.21), p=0.40]. Sixty-one patients presented with
a major cardiovascular event (stroke, myocardial infarction or cardiovascular death) during the
follow-up period. The un-adjusted analysis demonstrated no significant between-group
differences in the incidence of stroke [1 (0.8% person-year) patient in MT group compared with
10 (1.9% person-year) patients in MAT, HR (95%-CI) 2.3 (0.30-18.01), p=0.42], no in the
incidence of myocardial infarction [0 patients (0% person-year) in MT group vs. 5 (0.9% personyear) in MAT; p=0.49]. These data did not change following a Cox-adjusted analysis, showing
no differences between either antithrombotic strategies for the cumulative hazard ratio major
cardiovascular endpoint [8 patients (6.5% person-years) in MT group vs. 53 patients (9.0%
person-year) in MAT group; adjusted-HR (95% CI) 1.62 (0.74-3.55), p=0.23]. Fifty-eight
patients presented with a major or LTB [7 patients (6.0% person-year) in MT group vs. 51
(10.8% person-years) in MAT group; adjusted-HR 1.93 (0.85-4.42), p=0.12]. The combined
endpoint of stroke, MI or any type of bleeding was reported in 7 (6.0 % person-years) patients in
the MT group compared with 63 (13.4% person-years) in the MAT group [adjusted-HR (95%
CI) 2.41 (1.07-5.43), p=0.03] (Figure 1, supplemental materials)
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Figure 1. Kaplan Meier curves at 1-Year Follow-Up for Ischemic, Bleeding Events and
Death, According to Antithrombotic Therapy (landmark analysis)
Kaplan Meier curves at 1-year follow-up for the combined endpoint of stroke, MI or death (a),
for VARC-2 major or life-threatening bleeding (b), and for the combined endpoint of stroke, MI
or any type of bleeding (c) according to the antithrombotic strategy used (warfarin alone versus
warfarin plus antiplatelet therapy).
ATP: Anti-Platelet Therapy. LTB: Life-Threatening Bleeding. MI: Myocardial infarction (ST
elevation). VKA: Vitamin-K Antagonist group.
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Table 1. Baseline and procedural characteristics and in-hospital complications of patients
under mono-therapy versus double therapy (warfarin plus one APT).
Demographic and cardiovascular risk
factors
VKA
(n=101)
VKA + single APT
(n=463)
p
value
49 (48.5)
250 (54.0)
0.32
Sex, female
81.3 (7.0)
81.7 (6.5)
0.58
Age, years
37 (36.6)
160 (34.6)
0.73
Diabetes mellitus
1.70 (0.4)
1.74 (0.28)
0.32
Body surface area
3.1 (1.1)
3.3 (1.1)
0.16
101 (100)
463 (100)
Atrial fibrillation/flutter
75 (24)
225 (48.6)
<0.01
Coronary artery disease
10 (9.9)
123 (26.6)
<0.01
Previous PCI
20 (19.8)
117 (25.3)
0.31
Previous heart surgery
13 (12.9)
100 (21.6)
0.05
Previous CABG
20 (19.8)
92 (19.9)
1.0
64 (63.4)
258 (55.7)
0.18
52 (24)
49 (21)
0.31
22 (21.8)
132 (28.5)
0.18
17.7 (11.6)
20.9 (14.1)
0.04
28 (27.7)
260 (56.2)
<0.01
54.6 (13.6)
55.5 (14.7)
0.61
46.6 (16.8)
43.6 (16.4)
0.10
50.4 (17.1)
48.3 (14.8)
0.27
82 (81.2)
317 (68.5)
0.01
17 (16.8)
119 (25.7)
0.07
2 (2.0)
27 (5.8)
0.14
76 (75.2)
335 (73.0)
0.71
CHADS2 score
Cardiovascular history
Stroke/TIA
Other conditions
Renal failure (clearance < 60
ml/m)
Creatinine clearance, ml/m
COPD
Logistic EuroScore, %
Baseline Antiplatelet therapy
Echocardiographic characteristics
LVEF, %
Mean transaortic gradient, mmHg
PAPs, mmHg
Approach
Transfemoral approach
Transapical approach
Other approach
Prosthesis type
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Balloon expandable
25 (24.8)
126 (27.0)
0.71
6 (5.9)
20 (4.3)
0.44
86 (85.1)
314 (67.8)
<0.01
5 (5.0)
19 (4.1)
0.79
4 (4)
15 (3.2)
0.76
0 (0)
10 (2.2)
0.22
In-hospital MI
7 (7.0)
48 (10.5)
0.36
Major vascular complication
6 (5.9)
72 (15.6)
0.02
17 (16.8)
82 (17.7)
0.89
9 (8.9)
65 (14.0)
0.20
Self-expandable
Other procedural characteristics
Valve-in-valve procedure
Bridge with LMWH
In-Hospital complications
Death, any cause*
In-hospital stroke
Major bleeding or LTB
Acute kidney injury
Pacemaker implantation
Values are expressed as mean ± SD, or n (%).
All the in-hospital outcomes were defined following the VARC-2 criteria.
*
Excluded immediate procedural death (following VARC-2 definition)
APT: Anti-Platelet Therapy. CABG: Coronary Artery Bypass Grafting. CHADs2: Congestive
Heart failure, Hypertension, Age ≥75, Diabetes mellitus, and prior Stroke or transient ischemic
attack score2. COPD: Chronic Obstructive Pulmonary disease. EuroScore: European System for
Cardiac Operative Risk Evaluation. LVEF: Left Ventricular Ejection Fraction. LMWH: LowMolecular-Weight Heparin.
PAPs; Systolic Pulmonary Artery Pressure. PCI: Percutaneous Coronary Intervention. TIA:
Transient Ischemic Attack. VKA: Vitamin-K Antagonist group.
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Table 2. Baseline and procedural characteristics and in-hospital complications of patients
under mono-therapy versus triple therapy (warfarin plus dual APT).
Demographic and cardiovascular risk
factors
VKA
(n=101)
VKA + dual
APT (n=57)
p
value
49 (48.5)
33 (57.9)
0.32
Sex, female
81.3 (7.0)
80.7 (6.5)
0.58
Age, years
37 (36.6)
19 (33.3)
0.73
Diabetes mellitus
1.70 (0.4)
1.7 (0.21)
0.67
Body surface area
3.1 (1.1)
3.1 (1.2)
0.76
101 (100)
57 (100)
Atrial fibrillation/flutter
75 (24)
43 (75.4)
<0.01
Coronary artery disease
10 (9.9)
34 (59.6)
<0.01
Previous PCI
20 (19.8)
13 (22.8)
0.67
Previous heart surgery
13 (12.9)
11 (19.3)
0.36
Previous CABG
20 (19.8)
11 (19.3)
0.99
64 (63.4)
44 (77.2)
0.03
52 (24)
45 (18)
0.05
22 (21.8)
14 (24.6)
0.70
17.7 (11.6)
20.3 (15.2)
0.25
28 (27.7)
44 (72.2)
<0.01
54.6 (13.6)
53.9 (13.7)
0.75
46.6 (16.8)
44.2 (16.9)
0.36
50.4 (17.1)
44.9 (15.9)
0.06
82 (81.2)
42 (73.7)
0.32
17 (16.8)
13 (22.8)
0.40
2 (2.0)
2 (3.6)
0.62
76 (75.2)
33 (57.9)
0.03
CHADS2 score
Cardiovascular history
Stroke/TIA
Other conditions
Renal failure (clearance < 60
ml/m)
Creatinine clearance, ml/m
COPD
Logistic EuroScore, %
Baseline Antiplatelet therapy
Echocardiographic characteristics
LVEF, %
Mean transaortic gradient, mmHg
PAPs, mmHg
Approach
Transfemoral approach
Transapical approach
Other approach
Prosthesis type
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Balloon expandable
25 (24.8)
24 (42.1)
0.03
6 (5.9)
2 (3.5)
0.71
86 (85.1)
53 (93.0)
<0.01
5 (5.0)
3 (5.3)
1.0
Death, any cause*
4 (4)
4 (7)
0.46
In-hospital stroke
0 (0)
2 (3.5)
0.12
In-hospital MI
7 (7.0)
6 (10.5)
0.55
Major vascular complication
6 (5.9)
5 (8.8)
0.53
17 (16.8)
11 (19.3)
0.83
9 (8.9)
7 (12.3)
0.59
Self-expandable
Other procedural characteristics
Valve-in-valve procedure
Bridge with LMWH
In-Hospital complications
Major bleeding or LTB
Acute kidney injury
Pacemaker implantation
Values are expressed as mean ± SD, or n (%).
All the in-hospital outcomes were defined following the VARC-2 criteria.
*
Excluded immediate procedural death (following VARC-2 definition)
APT: Anti-Platelet Therapy. CABG: Coronary Artery Bypass Grafting. CHADs2: Congestive
Heart failure, Hypertension, Age ≥75, Diabetes mellitus, and prior Stroke or transient ischemic
attack score2. COPD: Chronic Obstructive Pulmonary disease. EuroScore: European System for
Cardiac Operative Risk Evaluation. LVEF: Left Ventricular Ejection Fraction. LMWH: LowMolecular-Weight Heparin.
PAPs; Systolic Pulmonary Artery Pressure. PCI: Percutaneous Coronary Intervention. TIA:
Transient Ischemic Attack. VKA: Vitamin-K Antagonist group.
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Table 3. Sensitivity analysis: effectiveness and safety outcomes (excluding patients who have not
changed the antithrombotic strategy following the first event)
Crude HR
[95% CI]
p
Adjusted HR
[95% CI]
p
0.92 [0.581.45]
0.73
0.92 [0.571.42]
0.71
Death
All-cause
Cardiovascular
Stroke or MI
Ischemic stroke
Hemorrhagic stroke
MI
Bleeding events
Any
VARC-2 Major or LTB
1.50 [0.455.00]
BARC type 2
Requiring transfusion
Combined Endpoints
Stroke or MI
CV Death, stroke or MI
Stroke, MI or bleeding
(all)
0.20
NP
0.37 [0.101.54]
0.16
NP
0.10
1.52 [0.852.73]
0.09
1.67 [0.913.05]
0.03
0.55 [0.142.12]
0.22
1.47 [0.336.48]
2.72 [1.096.77]
2.12 [0.637.07]
1.33 [0.722.44]
1.47 [0.872.49]
0.39
1.71 [0.505.83]
NP
NP
NP
0.38
1.90 [0.913.95]
0.78
1.10 [0.552.20]
0.51
BARC type 5 (fatal)
BARC type 3
0.74
1.12 [0.572.22]
0.61
NP
0.21
0.15
1.46 [0.812.63]
0.55
1.57 [0.852.90]
0.62
0.17
0.08
0.65 [0.162.60]
0.36
0.15
1.68 [0.803.53]
0.15
1.47 [0.33 6.54]
0.17
0.32
2.27 [0.905.71]
2.44 [0.738.12]
1.37 [0.742.55]
1.45 [0.852.47]
Values expressed as n (global %). In this table values are not expressed as a person-time unit.
APT: Anti-Platelet Therapy. BARC: Bleeding Academy Research Consortium. . CI: Confidence Interval.
HR: Hazard Ratio. LTB: Life-Threatening Bleeding. MI: Myocardial Infarction (ST elevation). NP: Not
Provided. VARC: Valve Academic Research Consensus. VKA: Vitamin-K Antagonist group
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