Patients characteristics
The study cohort comprised 548 patients, including 435 (79.4%) and 113 (20.6%) patients with and without postoperative CCB treatment, respectively. Among those treated with CCB, 31 (7.1%) patients were treated with CCB only within the first year whereas the remaining 404 (92.9%) patients were continuously treated with CCB for 1 year or longer. After matching, 101 patients in each group were considered to satisfy the conditions for final analyses (Figure 1).
Patients characteristics are shown in Table 1. Before matching, compared with the non-CCB group, the CCB group comprised higher rates of patients with grade ≥ 2 hypertension (79.3% vs. 55.8%, P < 0.001) and those treated with multiple anti-hypertensive drugs (beta-blocker, 97.2% vs. 90.3%, P = 0.003; ARB, 57.5% vs. 35.4%, P < 0.001; alpha-blocker, 15.9% vs. 3.5%, P = 0.001). In addition, the rate of patients undergoing TEVAR in the acute phase was higher, whereas the rate of patients undergoing hybrid produce was lower in the CCB group compared with the non-CCB group (71.0% vs. 58.4%, P = 0.010; 22.8% vs. 37.2%, P = 0.002). After matching, there were no significant differences in demographic characteristics, comorbidities, imaging characteristics, operative details and medication uses between the CCB and non-CCB groups (standard mean difference < 10% for all). The C-statistic of the model was 0.58, suggesting moderate predictive ability.
Table 1
Baseline characteristics
|
Unmatched cohort
(n=548)
|
Matched cohort
(n=206)
|
|
CCB
(n = 435)
|
Non-CCB
(n = 113)
|
P
|
SMD
|
CCB
(n = 101)
|
Non-CCB
(n = 101)
|
P
|
SMD
|
Demographic characteristics
|
|
|
|
|
|
|
|
|
Age (years)
|
54.4 ± 10.1
|
55.6 ± 11.9
|
0.284
|
0.109
|
56.2 ± 10.3
|
56.2 ± 11.4
|
0.928
|
0.007
|
Male
|
377 (86.7)
|
100 (88.5)
|
0.606
|
0.055
|
90 (89.1)
|
89 (88.1)
|
0.999
|
0.031
|
Comorbidities
|
|
|
|
|
|
|
|
|
Hypertension, grade ≥ 2
|
345 (79.3)
|
63 (55.8)
|
<0.001
|
0.518
|
61 (60.4)
|
63 (62.4)
|
0.864
|
0.040
|
Diabetes mellitus
|
33 (7.6)
|
9 (8.0)
|
0.893
|
0.014
|
7 (6.9)
|
8 (7.9)
|
0.999
|
0.038
|
Dyslipidaemia
|
63 (14.5)
|
13 (11.5)
|
0.414
|
0.088
|
14 (13.9)
|
13 (12.9)
|
0.999
|
0.029
|
Coronary heart disease
|
61 (14.0)
|
20 (17.7)
|
0.327
|
0.100
|
20 (19.8)
|
18 (17.8)
|
0.856
|
0.050
|
Renal dysfunction
|
52 (12.0)
|
10 (8.8)
|
0.353
|
0.102
|
12 (11.9)
|
10 (9.9)
|
0.815
|
0.063
|
Smoking
|
202 (46.4)
|
48 (42.5)
|
0.452
|
0.080
|
46 (45.5)
|
46 (45.5)
|
0.999
|
<0.001
|
Imaging characteristics
|
|
|
|
|
|
|
|
|
MAD (mm)
|
38.9 ± 8.2
|
39.0 ± 8.7
|
0.910
|
0.012
|
38.6 ± 7.5
|
39.2 ± 8.8
|
0.434
|
0. 076
|
Patent false lumen
|
323 (74.3)
|
75 (66.4)
|
0.094
|
0.173
|
65 (64.4)
|
67 (66.3)
|
0.860
|
0.041
|
Pleural effusion
|
207 (47.6)
|
45 (39.8)
|
0.140
|
0.157
|
42 (41.6)
|
42 (41.6)
|
0.999
|
<0.001
|
Pericardial effusion
|
19 (4.4)
|
5 (4.4)
|
0.999
|
0.003
|
4 (4.0)
|
5 (5.0)
|
0.999
|
0.048
|
Operative details
|
|
|
|
|
|
|
|
|
Acute TBAD
|
309 (71.0)
|
66 (58.4)
|
0.010
|
0.266
|
61 (60.4)
|
59 (58.4)
|
0.864
|
0.020
|
Stent length (mm)
|
185.0 (185.0–200.0)
|
200.0 (185.0– 205.0)
|
0.150
|
0.185
|
200.0 (185.0–205.0)
|
200.0 (185.0–205.0)
|
0.735
|
0.049
|
Hybrid procedure
|
99 (22.8)
|
42 (37.2)
|
0.002
|
0.318
|
34 (33.7)
|
35 (34.7)
|
0.999
|
0.021
|
Chimney stent
|
72 (16.6)
|
21 (18.6)
|
0.608
|
0.053
|
20 (19.8)
|
18 (17.8)
|
0.860
|
0.050
|
Distal bare stent
|
25 (5.7)
|
8 (7.1)
|
0.596
|
0.054
|
5 (5.0)
|
5 (5.0)
|
0.999
|
<0.001
|
Medication uses
|
|
|
|
|
|
|
|
|
Beta-blocker
|
423 (97.2)
|
102 (90.3)
|
0.003
|
0.290
|
96 (95.0)
|
95 (94.1)
|
0.999
|
0.043
|
ACEI
|
40 (9.2)
|
6 (5.3)
|
0.184
|
0.150
|
7 (6.9)
|
6 (5.9)
|
0.999
|
0.040
|
ARB
|
250 (57.5)
|
40 (35.4)
|
<0.001
|
0.453
|
38 (37.6)
|
40 (39.6)
|
0.860
|
0.040
|
Alpha-blocker
|
69 (15.9)
|
4 (3.5)
|
0.001
|
0.425
|
3 (3.0)
|
4 (4.0)
|
0.999
|
0.054
|
Values are mean ± standard deviation, median (interquartile range) or n (%).
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium-channel blocker; MAD, maximum aortic diameter; SMD, standard mean difference; TBAD, type B aortic dissection.
|
Overall outcomes
Outcomes of the study patients are shown in Table 2. In the unmatched cohort, the median follow-up period was 35.3 (IQR, 16.9–60.0) months and 31.8 (IQR, 16.7–60.0) months in the CCB and non-CCB groups, respectively (P = 0.447). AAE occurred in 52 (12.0%) and 29 (25.7%) patients in the CCB and non-CCB groups, respectively (P < 0.001). A total of 23 patients (4.2%) aorta-related mortality, including 9 cases (1.6%) of sudden death. Additionally, non-aorta-related mortality occurred in 14 (3.2%) and 3 (2.7%) patients in the CCB and non-CCB groups, respectively (P = 0.999). All patients reached target blood pressure at 3 months after TEVAE, and there were no differences in SBP and DBP between the CCB and non-CCB groups.
Table 2
Outcomes
|
Unmatched cohort
(n = 548)
|
Matched cohort
(n = 202)
|
|
CCB
(n = 435)
|
Non-CCB
(n = 113)
|
P
|
CCB
(n = 101)
|
Non-CCB
(n = 101)
|
P
|
Follow-up (years)
|
35.3 (16.9–60.0)
|
31.8 (16.7–60.0)
|
0.447
|
39.8 (17.8–60.0)
|
30.7 (15.9–60.0)
|
0.354
|
Adverse aortic events
|
52 (12.0)
|
29 (25.7)
|
<0.001
|
8 (7.9)
|
22 (21.8)
|
0.013
|
Aorta-related mortality
|
15 (3.4)
|
8 (7.1)
|
0.110
|
2 (2.0)
|
6 (5.9)
|
0.289
|
Reintervention
|
37 (8.5)
|
21 (18.6)
|
0.002
|
6 (5.9)
|
16 (15.8)
|
0.041
|
Aortic rupture
|
1 (0.2)
|
1 (0.9)
|
0.370
|
1 (1.0)
|
1 (1.0)
|
0.999
|
RTAD
|
7 (1.6)
|
2 (1.8)
|
0.999
|
0 (0)
|
2 (2.0)
|
-
|
Type I endoleak
|
8 (1.8)
|
4 (3.5)
|
0.281
|
1 (1.0)
|
4 (4.0)
|
0.375
|
Type II endoleak
|
9 (2.1)
|
4 (3.5)
|
0.318
|
4 (4.0)
|
2 (2.0)
|
0.687
|
Distal expansion
|
11 (2.5)
|
7 (6.2)
|
0.071
|
0 (0)
|
5 (5.0)
|
-
|
DSINE
|
1 (0.2)
|
3 (2.7)
|
0.029
|
0 (0)
|
2 (2.0)
|
-
|
Non-aorta-related mortality
|
14 (3.2)
|
3 (2.7)
|
0.999
|
4 (4.0)
|
2 (2.0)
|
0.687
|
SBP at 3 months (mmHg)
|
120.0 (111.0–126.0)
|
120.0 (111.0–126.0)
|
0.599
|
120.0 (113.5–126.0)
|
120.0 (111.0–126.0)
|
0.477
|
DBP at 3 months (mmHg)
|
70.0 (64.0–74.0)
|
70.0 (62.0–74.0)
|
0.670
|
70.0 (65.0–76.0)
|
70.0 (62.0–73.0)
|
0.102
|
Values are median (interquartile range) or n (%).
CCB, calcium-channel blocker; DBP, diastolic blood pressure; DSINE, distal stent graft-induced new entry; RTAD, retrograde type A dissection; SBP, systolic blood pressure.
|
Types and daily dosages of CCB are shown in Figure 2. The most common type of CCB was amlodipine (84.1%), followed by nifedipine (11.7%) and felodipine (4.1%). The AAE rate was not different between the patients treated with amlodipine (12.3%) and those treated with nifedipine (9.8%, P = 0.608) or felodipine (11.1%, P = 0.999). Furthermore, there was no difference in the AAE rate between the patients treated with 5 and 10 mg/day amlodipine (15.7% vs. 10.6%, P = 0.161), between those treated with 30 and 60 mg/day nifedipine (9.7% vs. 10.0%, P = 0.999) and between those treated with 5 and 10 mg/day felodipine (0 vs. 18.2%, P = 0.497).
In the unmatched cohort, the AAE incidence rates at 1, 3 and 5 years in the CCB group were 4.1, 3.7 and 3.3 per 1000 patients per year, respectively; those in the non-CCB group were 8.7, 6.3 and 7.3 per 1000 patients per year, respectively. The mean time to AAE were 54.1 [95% confidence interval (CI) 52.5–55.6] months and 50.0 (95% CI 46.1–53.4) months in the CCB and non-CCB groups, respectively. Log-rank test analysis revealed that the levels of freedom from AAE were significantly different between the 2 groups (P < 0.001; Figure 3A).
Propensity score matching analysis and outcomes
In the matched cohort, the median follow-up period was 39.8 (IQR, 17.8–60.0) months and 30.7 (IQR, 15.9–60.0) months in the CCB and non-CCB groups, respectively (P = 0.354). AAE occurred in 8 (7.9%) and 22 (21.8%) patients in the CCB and non-CCB groups, respectively (P = 0.013; Table 2).
The AAE incidence rates at 1, 3 and 5 years in the CCB group were 4.4, 2.6 and 2.1 per 1000 patients per year, respectively; those in the non-CCB group were 8.9, 6.1 and 6.3 per 1000 patients per year, respectively. The mean time to AAE were 55.8 (95% CI 53.0–58.6) months and 50.4 (95% CI 46.6–54.3) months in the CCB and non-CCB groups, respectively. Log-rank test analysis revealed that the levels of freedom from AAE were significantly different between the 2 groups (P = 0.007; Figure 3B).
Multivariable analysis
The results of univariable and multivariable analyses are shown in Table 3. In the unmatched cohort, CCB use [hazard ratio (HR) 0.50, 95% CI 0.32–0.80; P = 0.003] was associated with a significantly lower AAE rate after adjustment for other risk factors. However, beta-blocker, ACEI, ARB and alpha-blocker did not show significant associations with a lower AAE rate. Furthermore, for each 1-mm increase in maximum aortic diameter, the AAE rate increased 1.04 times (95% CI 1.02–1.06; P < 0.001). Hybrid procedure (HR 2.41, 95% CI 1.54–3.77; P < 0.001) was also an independent risk factor for AAE. In the matched cohort, the association between CCB use and AAE rate was minimally changed (HR 0.34, 95% CI 0.15–0.75; P = 0.008).
Table 3
Univariable and multivariable predictors of adverse aortic events
|
Univariable analysis
|
Multivariable analysis
|
Multivariable analysis
propensity adjusted
|
|
HR (95%CI)
|
P
|
HR (95%CI)
|
P
|
HR (95%CI)
|
P
|
CCB
|
0.45 (0.29–0.71)
|
0.001
|
0.50 (0.32–0.80)
|
0.003
|
0.34 (0.15–0.75)
|
0.008
|
Demographic characteristics
|
|
|
|
|
|
|
Age (for each 1-year increase)
|
1.0 1 (0.99–1.03)
|
0.494
|
-
|
-
|
-
|
-
|
Male
|
1.20 (0.58–2.49)
|
0.627
|
-
|
-
|
-
|
-
|
Comorbidities
|
|
|
|
|
|
|
Hypertension, Grade≥2
|
0.98 (0.60– 1.62)
|
0.949
|
-
|
-
|
-
|
-
|
Diabetes
|
0.76 (0.31–1.87)
|
0.543
|
-
|
-
|
-
|
-
|
Dyslipidaemia
|
1.16 (0.63–2.14)
|
0.637
|
-
|
-
|
-
|
-
|
Coronary heart disease
|
1.03 (0.56–1.91)
|
0.917
|
-
|
-
|
-
|
-
|
Renal dysfunction
|
0.68 (0.30–1.56)
|
0.362
|
-
|
-
|
-
|
-
|
Smoking
|
0.70 (0.45–1.10)
|
0.119
|
-
|
-
|
-
|
-
|
Imaging characteristics
|
|
|
|
|
|
|
MAD (for each 1-mm increase)
|
1.04 (1.02–1.06)
|
0.001
|
1.04 (1.02–1.06)
|
<0.001
|
1.06 (1.03–1.10)
|
<0.001
|
Patent false lumen
|
1.09 (0.66–1.78)
|
0.747
|
-
|
-
|
-
|
-
|
Pleural effusion
|
1.02 (0.66–1.58)
|
0.938
|
-
|
-
|
-
|
-
|
Pericardial effusion
|
1.13 (0.41–3.08)
|
0.813
|
-
|
-
|
-
|
-
|
Operative details
|
|
|
|
|
|
|
Acute TBAD
|
0.95 (0.60–1.51)
|
0.825
|
-
|
-
|
-
|
-
|
Stent length (for each 1-mm increase)
|
1.01 (1.00–1.02)
|
0.077
|
-
|
-
|
-
|
-
|
Hybrid procedure
|
2.60 (1.68–4.03)
|
<0.001
|
2.41 (1.54–3.77)
|
<0.001
|
3.11 (1.50–6.43)
|
0.002
|
Chimney stent
|
1.07 (0.56–2.03)
|
0.849
|
-
|
-
|
-
|
-
|
Distal bare stent
|
1.54 (0.71–3.35)
|
0.274
|
-
|
-
|
-
|
-
|
Medication uses
|
|
|
|
|
|
|
Beta-blocker
|
0.97 (0.31–3.08)
|
0.960
|
-
|
-
|
-
|
-
|
ACEI
|
0.84 (0.37–1.93)
|
0.678
|
-
|
-
|
-
|
-
|
ARB
|
0.93 (0.60–1.43)
|
0.736
|
-
|
-
|
-
|
-
|
Alpha-blocker
|
1.31 (0.72–2.37)
|
0.372
|
-
|
-
|
-
|
-
|
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium-channel blocker; CI, confidence interval; HR, hazard ratio; MAD, maximum aortic diameter.
|