From January 2017 to December 2019, 546 patients with CCS and AF who had undergone PCI and were indicated to use OAC based on CHA2DS2-VASc score ≥1, excluding sex, were included in the final analysis. During the follow-up period, 30 patients withdrew their consent. Consequently, the analysis of the prognosis of CCS with AF patients who had undergone PCI comprised 519 patients. The median follow-up time was 36 months (interquartile range:22-45).
Baseline characteristics, organized by the year of enrollment, were presented in Table 1. The average age was 65.83±8.73 and 103 (18.7%) were female. Those enrolled in 2018 exhibited a slightly higher prevalence of hyperlipidemia. However, other demographic information and the history of comorbidities showed no difference among groups.
Table 1 Baseline characteristics according to enrolled years
Variables
|
2017 (n=210)
|
2018 (n=181)
|
2019(n=155)
|
Total (n=546)
|
P value*
|
Age
Female
|
65.96±9.14
42(20.0%)
|
65.08±8.67
35(19.3%)
|
66.37±8.23
23(14.8%)
|
65.78±8.73
100(18.3%)
|
0.376
0.411
|
BMI
|
25.96±3.55
|
26.15±3.27a
|
25.69±3.25
|
25.94±3.37
|
0.471
|
SBP
|
131.95±16.63
|
132.64±17.48
|
134.91±17.34
|
132.02±17.13
|
0.247
|
DBP
|
78.07±10.94
|
78.36±12.05
|
77.64±10.67
|
78.04±11.23
|
0.842
|
LVEF
|
59.87 ±7.72
|
58.71±9.24
|
59.39±7.84
|
59.35±8.29
|
0.387
|
CrCl
|
81.75
(68.42-95.93)
|
79.39
(70.61-91.54)
|
75.26
(64.80-89.02)
|
79.31
(67.57-92.20)
|
0.019
|
HAb1c
|
6.1 (5.8-7.0) b
|
6.2 (5.9-7.0)
|
6.3 (5.9-7.1)
|
6.2 (5.6-7.0)
|
0.193
|
Current smoker
|
54(25.7%)
|
42(23.2%)
|
26(16.8%)
|
122(22.3%)
|
0.121
|
HAS-BLED score≥3
|
64(30.5%)
|
61(33.7%)
|
57(36.8%)
|
182(33.3%)
|
0.447
|
CHA2DS2-VASc score
|
3 (2-4)
|
3 (2-4)
|
3 (2-4)
|
3 (2-4)
|
0.535
|
Medical history
|
|
|
|
|
|
MI
|
44(21.0%)
|
47(26.0%)
|
46(29.7%)
|
137(25.1%)
|
0.155
|
PCI
|
66(31.4%)
|
48(26.5%)
|
40(25.8%)
|
154(28.2%)
|
0.412
|
DM
|
87 (41.4%)
|
68 (37.6%)
|
63 (40.6%)
|
218 (39.9%)
|
0.771
|
HT
|
165 (78.6%)
|
147 (81.2%)
|
124 (80.0%)
|
436 (79.9%)
|
0.808
|
HF
|
33 (15.7%)
|
23 (12.7%)
|
30 (19.4%)
|
86 (15.8%)
|
0.249
|
CAD
|
161(76.7%)
|
133(73.5%)
|
106(68.4%)
|
400(73.3%)
|
0.209
|
PAD
|
32(15.2%)
|
30(16.6%)
|
23(14.8%)
|
85(15.6%)
|
0.896
|
CKD
|
10 (4.8%)
|
7 (3.9%)
|
6 (3.9%)
|
23 (4.2%)
|
0.880
|
CABG
|
11 (5.2%)
|
7 (3.9%)
|
12 (7.7%)
|
30 (5.5%)
|
0.293
|
TIA/stroke
|
52 (24.8%)
|
44 (24.3%)
|
39 (25.2%)
|
135 (24.7%)
|
0.984
|
Bleeding
|
13 (6.2%)
|
9 (5.0%)
|
8 (5.2%)
|
30 (5.5%)
|
0.850
|
Hyperlipidemia
|
156(74.3%)
|
153(84.5%)
|
111(71.6%)
|
420(76.9%)
|
0.010
|
Hyperthyroidism
|
22(10.5%)
|
14(7.7%)
|
10(6.5%)
|
46(8.4%)
|
0.361
|
AF type
|
|
|
|
|
|
New-onset AF
|
10(4.8%)
|
15(8.3%)
|
10(6.5%)
|
35(6.4%)
|
0.365
|
PAF
|
121(57.6%)
|
101(55.8%)
|
93(60.0%)
|
315(57.7%)
|
0.739
|
PeAF
|
79(37.6%)
|
65(35.9%)
|
52(33.5%)
|
196(35.9%)
|
0.725
|
a-1 patient missing; b-2 patients missing
Data are presented as number(percentage), mean ± SD or median (interquartile range)
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention; DM, diabetes mellitus; HT, hypertension; HF, heart failure; CAD, stable coronary artery disease; PAD, peripheral arterial disease; CKD, chronic kidney disease; CABG, coronary artery bypass grafting; TIA, transient ischemic attack; CrCl, creatine clearance; HAb1c, glycosylated hemoglobin; AF, atrial fibrillation; PAF, paroxysmal atrial fibrillation; PeAF, persistent atrial fibrillation and permanent atrial fibrillation.
*p value was based on χ2test, ANOVA and Kruskal-Wallis test as appropriate.
Status of antithrombotic therapy
The status of antithrombotic therapy according to the years of enrollment were presented in supplementary table 1. The utilization of clopidogrel and ticagrelor remained stable across the years without any significant differences. The prescription of aspirin showed a slight decrease. There was a notable increase in the usage of OAC (p<0.001), primarily attributed to the rising trend of NOAC usage. In contrast, the usage of warfarin showed no significant difference among the groups. DAT showed an increasing trend (p=0.022). Similarly, there was a significant increase in the group recieving TAT (p<0.001).
Figure 2 illustrated a decreasing trend in MACE events, stroke/TIA, MI and SE, while TIMI bleeding events showed an increasing pattern.
Subgroup analysis by antithrombotic therapy and OAC usage
The characteristics of patients according to antithrombotic therapy were presented in Table 3. Patients with lower creatine clearance (CrCl, p=0.046) preferred DAT. Those with lower left ventricular ejection fraction (LVEF) tended to be prescribed with TAT (p=0.042). Besides, non-OAC therapy was more likely to be utilized in patients with paroxysmal AF (PAF, p<0.001) and hyperlipidemia (p<0.001). On the other hand, patients with persist or permanent AF (PeAF, p<0.001), diabetes mellitus (DM, p=0.011) or heart failure (HF, p=0.023) were more likely to be prescribed with OAC. Therefore, higher HAb1c (p=0.016) was also observed in the combination therapy groups. In the comparison between the TAT and non-TAT groups, a higher BMI was associated with TAT therapy.
Details of the proportion of OAC usage in patients prescribed with TAT were shown in Figure 3, with rivaroxaban divided into five parts according to the daily prescription dose. Dabigatran was administered at 220mg daily, and the dose of VKA was tailored for individual patients. Overall, only 46.7% used the standard dose for stroke prevention.
Figure 4 depicted the percentage of events according to antithrombotic therapy during the follow-up period. MACE events showed differences between TAT and antiplatelet therapy. TIMI bleeding events presented differences between combined therapy (antiplatelet therapy plus OAC) and antiplatelet therapy. Similar results were detected in ischemia-driven revascularization.
As demonstrated in the supplementary table, OAC therapy was more likely to be administered to patients with a history of DM (p=0.003), a diagnosis with HF (p=0.006), and less likely in those diagnosed with hyperlipidemia (p<0.001). In addition, patients with PAF (p<0.001) were favored of non-OAC treatment, while patients with peAF (p<0.001) exhibited the opposite preference. Furthermore, peak cardiac troponin I (cTnI, p<0.001) and N-terminal pro-B-type natriuretic peptide (NT-proBNP, p<0.001) also presented an association with OAC usage.
Subsequently, the multivariate logistic regression analysis was performed to assess independent factors capable of predicting the prescription of OAC therapy (Figure 5). After adjustment for multivariate factors, peak cTnI and NT-proBNP showed no influence on OAC choice. However, patients with a history of DM (OR=2.033; 95%CI, 1.357-3.046), HF (OR=2.177; 95%CI, 1.295-3.659) and HT (OR=2.110; 95%CI, 1.256-3.545) were favored of OAC therapy. Notably, HF emerged as the strongest predictor of OAC prescription. Conversely, hyperlipidemia (OR=0.308; 95%CI, 0.194-0.490) and PAF (OR=0.294; 95%CI, 0.197-0.437) were associated with a preference for non-OAC therapy.
Table 3 Characteristics of patients according to antithrombotic therapy regimen
|
Non-TAT
(n=381)
|
TAT
(n=165)
|
P value#
|
P value*
|
|
Antiplatelet
(n=356)
|
DAT
(n=25)
|
|
|
|
Age
|
65.61±9.15
|
69.72±7.63
|
65.56±7.82
|
0.683
|
0.069
|
Female
|
66(18.5%)
|
8(32.0%)
|
26(15.8%)
|
0.309
|
0.145
|
BMI
|
25.78±3.35
|
25.12±3.75
|
26.43±3.33
|
0.031
|
0.062
|
SBP
|
133.84±17.69
|
133.88±17.47
|
131.12±15.73
|
0.074
|
0.212
|
DBP
|
78.45±11.61
|
73.44±10.77
|
77.87±10.32
|
0.808
|
0.095
|
CrCl
|
80.81
(70.25-93.59)
|
74.85
(67.59-89.14)
|
76.03
(65.81-90.74)
|
0.137
|
0.046
|
LVEF
|
60.02±7.69
|
59.16±9.31
|
57.94±9.20
|
0.029
|
0.029
|
HAb1c
|
6.16(5.80-6.90)
|
6.20(5.90-7.05)
|
6.40(5.90-7.40)
|
0.005
|
0.016
|
AF type
|
|
|
|
|
|
New-onset
|
22 (6.2%)
|
1 (4.0%)
|
12 (7.3%)
|
0.588
|
0.787
|
PAF
|
243 (68.3%)
|
14 (56.0%)
|
58 (35.2%)
|
<0.001
|
<0.001
|
PeAF
|
91(25.6%)
|
10(40.0%)
|
95(57.6%)
|
<0.001
|
<0.001
|
Medical history
|
|
|
|
|
|
HT
|
276 (77.5%)
|
23 (92.0%)
|
137 (83.0%)
|
0.223
|
0.104
|
HF
|
45(12.6%)
|
5(20.0%)
|
36(21.8%)
|
0.010
|
0.023
|
DM
|
126 (35.4%)
|
11 (44.0%)
|
81 (49.1%)
|
0.004
|
0.011
|
Hyperlipidemia
|
298 (83.7%)
|
16 (64.0%)
|
106 (64.2%)
|
<0.001
|
<0.001
|
Stroke/TIA
|
79 (22.2%)
|
8 (32.0%)
|
48 (29.1%)
|
0.120
|
0.163
|
Bleeding
|
20(5.6%)
|
0(0.0%)
|
10(6.1%)
|
0.702
|
0.457
|
HAS-BLED score≥3
|
111 (31.2%)
|
12 (48.0%)
|
59 (35.8%)
|
0.429
|
0.165
|
Data are presented as number(percentage), mean ± SD or median (interquartile range)
DAT, double antithrombotic therapy; TAT, triple antithrombotic therapy; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CrCl, creatine clearance; LVEF, left ventricular ejection fraction; HAb1c, glycosylated hemoglobin; HT, hypertension; HF, heart failure; DM, diabetes mellitus; PAF, paroxysm atrial fibrillation; PeAF includes persist atrial fibrillation and permanent atrial fibrillation; TIA, Transient ischemic attack
# p value was based on χ2 test, t test and Wilcoxon Mann Whitney as appropriate between non-TAT and TAT.
* p value was based on χ2 test, ANOVA and Kruskal-Wallis test as appropriate among antiplatelet, DAT and TAT.
Prognosis of patients with CCS and AF underwent PCI
Regarding the prognosis, we conducted separate analyses for MACE events and TIMI bleeding events, respectively. After adjusting for potentially confounding variables through multivariate Cox regression, a history of HF (HR, 1.744; 95%CI, 1.011-3.038) and TAT (HR, 2.708; 95%CI, 1.653-4.436) showed an independent association with MACE events, as detailed in Table 4.
In terms of bleeding events, there was a decrease in the risk of bleeding with an increase in CrCl (HR, 0.986; 95%CI, 0.974-0.997). On the other hand, OAC therapy (HR, 10.378; 95%CI, 6.136-17.555) emerged as a risk factor for TIMI bleeding events. (Table 4)
Table 4 Predictors with hazard ratio (HR) and 95%CI for MACE events and TIMI bleeding events
Variates
|
HR
|
95%CI
|
P value
|
MACE events
|
|
|
|
HF
|
1.744
|
1.011-3.038
|
0.050
|
TAT
|
2.708
|
1.653-4.436
|
<0.001
|
TIMI bleeding events
|
|
|
|
CrCl
|
0.986
|
0.974-0.997
|
0.014
|
OAC
|
10.378
|
6.136-17.555
|
<0.001
|
CI, confidential interval; HF, heart failure; TAT, triple antithrombotic therapy
MACE events included all-cause death, myocardial infarction, stroke, systemic embolism or ischemia-driven revascularization.
CrCl, creatine clearance; OAC, oral anticoagulant
TIMI bleeding events included minor, minimal and major TIMI bleeding events based on TIMI criteria.