A total of 1836 patients diagnosed as having AMI from January 2016 to December 2019 were included in this study. One hundred and thirty-five patients who had incomplete data, received incomplete DAPT, were lost to follow-up, or did not undergo PCI were excluded. Of the 1836 patients, 938 patients were diagnosed as having NSTEMI and 898 were diagnosed as having STEMI. Moreover, 929 patients were included in the ticagrelor group, whereas 772 patients were included in the clopidogrel group (Fig. 1).
The patients’ baseline characteristics are presented in Table 1. Patients in the clopidogrel group were older than those in the ticagrelor group (65.63 ± 13.49 versus 59.37 ± 13.08 years, P < .001). Although men were predominant in the two groups, the percentage of men was higher in the ticagrelor group (82.24% versus 71.89%, P < .001). Patients in the clopidogrel group had a higher prevalence of underlying diseases, such as hypertension (62.56% versus 54.79%, P = .001), diabetes mellitus (43.65% versus 31.75%, P < .001), coronary artery disease (29.53% versus 16.79%, P < .001), cerebrovascular events (7.90% versus 2.91%, P < .001), and chronic kidney disease (22.54% versus 9.36%, P < .001). Patients in the ticagrelor group had a higher prevalence of smoking (57.80% versus 47.80%, P < .001) and hyperlipidemia (9.15% versus 5.31%, P = .002).
Table 1
Variables
|
Drug
|
p-value
|
Clopidogrel
(n = 772)
|
Ticagrelor
(n = 929)
|
Age, mean ± SD
|
65.63 ± 13.49
|
59.37 ± 13.08
|
< 0.001a
|
Sex, (%)
|
|
|
< 0.001b
|
Male
|
555(71.89)
|
764(82.24)
|
|
Female
|
217(28.11)
|
165(17.76)
|
|
Clinical History, (%)
|
|
|
|
Smoking
|
369(47.80)
|
537(57.80)
|
< 0.001b
|
Hypertension
|
483(62.56)
|
509(54.79)
|
0.001b
|
Diabetes mellitus
|
337(43.65)
|
295(31.75)
|
< 0.001b
|
Coronary artery disease
|
228(29.53)
|
156(16.79)
|
< 0.001b
|
Cerebrovascular disease
|
61(7.90)
|
27(2.91)
|
< 0.001b
|
Chronic kidney disease
|
174(22.54)
|
87(9.36)
|
< 0.001b
|
Hyperlipidemia
|
41(5.31)
|
85(9.15)
|
0.002b
|
Presentation feathers
|
|
|
|
Killip class
|
|
|
|
Level 2-Level 4
|
182(23.58)
|
145(15.61)
|
< 0.001b
|
Systolic BP (SBP)
|
136.5 ± 39.21
|
135.2 ± 32.56
|
0.472a
|
Diastolic BP (DBP)
|
83.55 ± 26.71
|
86.06 ± 22.75
|
0.039a
|
Heart rate, bpm
|
85.96 ± 27.09
|
83.27 ± 22.56
|
0.028a
|
Peak Troponin I, ng/mL
|
5.19 ± 11.53
|
3.60 ± 9.36
|
0.002a
|
GFR
|
54.10 ± 34.35
|
67.52 ± 27.88
|
< 0.001a
|
Creatinine
|
2.64 ± 3.10
|
1.67 ± 3.88
|
< 0.001a
|
LVEF
|
49.99 ± 12.17
|
50.36 ± 11.23
|
0.535a
|
Angiographic findings
|
|
|
|
Left main disease*
|
54(6.99)
|
56(6.03)
|
0.419b
|
No. of disease vessels*
|
|
|
0.107b
|
1
|
355(45.98)
|
445(47.90)
|
|
2
|
250(32.38)
|
293(31.54)
|
|
3
|
111(14.38)
|
148(15.93)
|
|
No. of disease vessels*
|
|
|
0.374b
|
<3
|
661(85.62)
|
781(84.07)
|
|
≧3
|
111(14.38)
|
148(15.93)
|
|
Type
|
|
|
< 0.001b
|
STEMI
|
292(37.82)
|
543(58.45)
|
|
NSTEMI
|
480(62.18)
|
386(41.55)
|
|
Data are presented as the means ± standard deviations for continuous variables and numbers (percentages) for categorical variables. aTwo-sample t test. bChi-squared test. *Significant disease refers to > 75% stenosis of a coronary artery, except in left main coronary artery disease (stenosis > 50%).
BP: blood pressure; GFR: glomerular filtration rate; LVEF: left ventricular ejection fraction; STEMI: ST-elevation myocardial infarction; NSTEMI: non-ST-elevation myocardial infarction.
Assessment of the clinical features at presentation revealed that the clopidogrel group had a higher Killip score (II to IV) (23.58% versus 15.61%, P < .001), higher peak troponin I level (5.19 ± 11.53 ng/mL versus 3.60 ± 9.36 ng/mL, P = .002), and higher creatinine level (2.64 ± 3.10 mg/dL versus 1.67 ± 3.88 mg/dL, P < .001).
The ticagrelor group had more patients with STEMI than the clopidogrel group (58.45% versus 37.82%, P < .001). By contrast, the clopidogrel group had more patients with NSTEMI than the ticagrelor group (41.55% versus 62.18%, P < .001). No significant difference was noted in the LVEF or significant coronary lesions (defined as > 50% stenosis of the left main coronary artery or > 75% stenosis of other coronary arteries) between the 2 groups (Table 1).
Patients in the ticagrelor group had better outcomes in terms of the in-hospital MACE rate than those in the clopidogrel group (3.01% versus 7.51%, P < .001). Moreover, the in-hospital mortality rate was lower in the ticagrelor group (2.15% versus 5.70%, P < .001). No significant difference was noted in the incidence of in-hospital stroke or recurrent MI between the 2 groups. The rate of PCI procedures performed within 30 days was higher in the ticagrelor group (17.22% versus 13.73%, P = .048); however, no significant difference was noted in other secondary outcomes, such as return to the ED within 72 hours, readmission within 14 days, or CABG surgery performed within 30 d after discharge (Table 2).
Table 2
Patient Outcomes in Each Group
Variables
|
Drug
|
p-value
|
Clopidogrel
(n = 772)
|
Ticagrelor
(n = 929)
|
In-hospital MACE, (%)
|
|
|
< 0.001b
|
No
|
714(92.49)
|
901(96.99)
|
|
Stroke
|
10(1.30)
|
5(0.54)
|
|
Recurrent MI
|
1(0.13)
|
2(0.22)
|
|
Rupture PCI
|
3(0.39)
|
1(0.11)
|
|
Death
|
44(5.70)
|
20(2.15)
|
|
72 hours ED return, (%)
|
|
|
0.096b
|
No
|
768(99.48)
|
925(99.57)
|
|
Planned
|
0(0.00)
|
3(0.32)
|
|
Unplanned
|
4(0.52)
|
1(0.11)
|
|
14 days readmission, (%)
|
|
|
0.096b
|
No
|
755(97.80)
|
919(98.92)
|
|
Planned
|
8(1.04)
|
7(0.75)
|
|
Unplanned
|
9(1.17)
|
3(0.32)
|
|
PCI performed within 30 days
|
106(13.73)
|
160(17.22)
|
0.048b
|
CABG performed within 30 days
|
5(0.65)
|
10(1.08)
|
0.346b
|
aTwo-sample t test. bChi-squared test.
MACE: major adverse cardiovascular event; MI: myocardial infarction; PCI: percutaneous coronary intervention; ED: emergency department; CABG: coronary artery bypass graft.
Age, clopidogrel use, hypertension, diabetes mellitus, cerebrovascular disease, higher Killip scores, higher peak troponin I levels, left main coronary artery disease, and STEMI were associated with increased MACE rates in our univariate analysis. However, ticagrelor use, smoking, and high blood pressure were associated with decreased MACE rates. Variables that were significantly associated with MACEs in univariate logistic regression analysis and were reported as important prognostic factors in previous studies,(11, 12) namely age, sex, ticagrelor or clopidogrel use, smoking, hypertension, diabetes mellitus, cerebrovascular disease, Killip score, peak troponin I level, blood pressure, left main coronary artery disease, and STEMI or NSTEMI, were selected for multivariate analysis in our study. Multivariate logistic regression analysis revealed that older age (odds ratio [OR]: 1.05, 95% CI: 1.03–1.07, P < .001), higher Killip scores (OR: 3.77, 95% CI: 2.32–6.11, P < .001), higher peak troponin I levels (OR: 1.02, 95% CI: 1.01–1.03, P = .027), and STEMI (OR: 2.39, 95% CI: 1.43–3.98, P < .001) were associated with higher in-hospital MACE rates. By contrast, loading of ticagrelor in the ED (OR: 0.51, 95% CI: 0.31–0.85, P = .01) and higher systolic blood pressure (OR: 0.99, 95% CI: 0.98–0.99, P = .001) were associated with lower in-hospital MACE rates (Table 3).
Table 3
Univariate and Multivariate Analyses of In-Hospital MACE Rates
Parameters
|
Univariate
|
Multivariate
|
OR (95% CI)
|
p-value
|
OR (95% CI)
|
p-value
|
Age
|
1.06(1.04–1.08)
|
< 0.001
|
1.05(1.03–1.07)
|
< 0.001
|
Sex, Male
|
0.65(0.41–1.05)
|
0.078
|
1.16(0.66–2.04)
|
0.604
|
Drug
|
|
|
|
|
clopidogrel
|
Ref.
|
-
|
Ref.
|
-
|
ticagrelor
|
0.38(0.24–0.61)
|
< 0.001
|
0.53(0.32–0.88)
|
0.013
|
Clinical History
|
|
|
|
|
Smoking
|
0.53(0.34–0.83)
|
0.005
|
0.86(0.50–1.46)
|
0.567
|
Hypertension
|
1.60(1.01–2.55)
|
0.048
|
1.12(0.66–1.89)
|
0.677
|
Diabetes mellitus
|
1.58(1.02–2.44)
|
0.039
|
1.08(0.66–1.77)
|
0.769
|
Coronary artery disease
|
1.27(0.78–2.07)
|
0.343
|
|
|
Cerebrovascular disease
|
3.28(1.71–6.30)
|
< 0.001
|
1.75(0.84–3.64)
|
0.133
|
Chronic kidney disease
|
1.18(0.66–2.09)
|
0.579
|
|
|
Hyperlipidemia
|
0.76(0.30–1.92)
|
0.564
|
|
|
Presentation feathers
|
|
|
|
|
Killip class
|
|
|
|
|
Level 1
|
Ref.
|
-
|
Ref.
|
-
|
Level 2-Level 4
|
6.37(4.08–9.95)
|
< 0.001
|
3.77(2.32–6.11)
|
< 0.001
|
Systolic BP (SBP)
|
0.99(0.98–0.99)
|
< 0.001
|
0.99(0.98–0.99)
|
0.001
|
Diastolic BP (DBP)
|
0.98(0.97–0.99)
|
< 0.001
|
|
|
Heart rate
|
1.00(0.99–1.01)
|
0.365
|
|
|
Peak Troponin I
|
1.02(1.01–1.04)
|
0.001
|
1.02(1.01–1.03)
|
0.027
|
Angiographic findings
|
|
|
|
|
Left main disease*
|
2.25(1.16–4.37)
|
0.017
|
1.82(0.87–3.82)
|
0.110
|
No. of disease vessels*
|
|
|
|
|
<3
|
Ref.
|
-
|
|
|
≧3
|
1.63(0.96–2.75)
|
0.071
|
|
|
Type
|
|
|
|
|
NSTEMI
|
Ref.
|
-
|
Ref.
|
-
|
STEMI
|
1.71(1.10–2.67)
|
0.018
|
2.39(1.43–3.98)
|
< 0.001
|
*Significant disease refers to > 75% stenosis of a coronary artery, except in left main coronary artery disease (stenosis > 50%).
NSTEMI: non-ST-elevation myocardial infarction; STEMI: ST-elevation myocardial infarction.
After 1:1 matching with age, sex, prior coronary artery disease, prior cerebrovascular disease and STEMI or NSTEMI, 594 patients in each group were selected for further analysis. The demographic characteristics of two groups were compared as Table 4.
Table 4
After 1:1 Propensity Score Matching Patient Characteristics
Variables
|
Drug
|
p-value
|
Clopidogrel
(n = 594)
|
Ticagrelor
(n = 594)
|
Age, mean ± SD
|
63.37 ± 13.27
|
63.06 ± 12.85
|
0.680a
|
Sex, (%)
|
|
|
0.530b
|
Male
|
457(76.94)
|
466(78.45)
|
|
Female
|
137(23.06)
|
128(21.55)
|
|
Clinical History, (%)
|
|
|
|
Smoking
|
309(52.02)
|
315(53.03)
|
0.727b
|
Hypertension
|
352(59.26)
|
347(58.42)
|
0.768b
|
Diabetes Mellitus
|
239(40.24)
|
208(35.02)
|
0.063b
|
Coronary artery disease
|
129(21.72)
|
123(20.71)
|
0.670b
|
Cerebrovascular disease
|
19(3.20)
|
24(4.04)
|
0.437b
|
Chronic kidney disease
|
114(19.19)
|
69(11.62)
|
< 0.001b
|
Hyperlipidemia
|
27(4.55)
|
55(9.26)
|
0.001b
|
Presentation feathers
|
|
|
|
Killip class
|
|
|
|
Level 2-Level 4
|
131(22.05)
|
95(15.99)
|
0.007b
|
Systolic BP (SBP)
|
135.3 ± 40.68
|
136.3 ± 31.77
|
0.640a
|
Diastolic BP (DBP)
|
83.69 ± 27.70
|
85.49 ± 22.23
|
0.217a
|
Heart rate, bpm
|
84.26 ± 27.05
|
84.10 ± 22.32
|
0.910a
|
Peak Troponin I, ng/mL
|
4.71 ± 10.46
|
4.13 ± 9.87
|
0.321a
|
GFR
|
58.09 ± 34.20
|
63.30 ± 28.88
|
0.004a
|
Creatinine
|
2.47 ± 3.08
|
1.90 ± 4.74
|
0.013a
|
LVEF
|
50.29 ± 12.51
|
50.60 ± 11.09
|
0.663a
|
Angiographic findings
|
|
|
|
Left main disease*
|
33(5.56)
|
44(7.41)
|
0.194b
|
No. of disease vessels*
|
|
|
0.315b
|
1
|
284(47.81)
|
273(45.96)
|
|
2
|
188(31.65)
|
188(31.65)
|
|
3
|
83(13.97)
|
103(17.34)
|
|
No. of disease vessels*
|
|
|
0.110b
|
<3
|
511(86.03)
|
491(82.66)
|
|
≧3
|
83(13.97)
|
103(17.34)
|
|
Type
|
|
|
0.682b
|
STEMI
|
269(45.29)
|
262(44.11)
|
|
NSTEMI
|
325(54.71)
|
332(55.89)
|
|
Data are presented as the means ± standard deviations for continuous variables and numbers (percentages) for categorical variables. aTwo-sample t test. bChi-squared test. *Significant disease refers to > 75% stenosis of a coronary artery, except in left main coronary artery disease (stenosis > 50%).
BP: blood pressure; GFR: glomerular filtration rate; LVEF: left ventricular ejection fraction; STEMI: ST-elevation myocardial infarction; NSTEMI: non-ST-elevation myocardial infarction.
The conditional logistic regression for the matched cohort revealed a lower risk of in-hospital MACE among ticagrelor group than clopidogrel group (OR 0.41, 95% CI0.18–0.91, P = 0.028) and higher Killip levels had a higher risk of in hospital MACE (OR 10.20, 95% CI 2.13–48.76, P = 0.003) (Table 5.)
Table 5
After 1:1 Propensity score matching Univariate and multivariate analysis for in-hospital MACE rates (conditional logistic regression)
Parameters
|
Univariate
|
Multivariate
|
OR (95% CI)
|
p-value
|
OR (95% CI)
|
p-value
|
Age
|
1.05(0.99–1.11)
|
0.120
|
0.96(0.84–1.09)
|
0.499
|
Sex, Male
|
0.29(0.06–1.38)
|
0.118
|
1.66(0.05–52.55)
|
0.773
|
Drug
|
|
|
|
|
clopidogrel
|
Ref.
|
-
|
Ref.
|
-
|
ticagrelor
|
0.42(0.25–0.70)
|
0.001
|
0.41(0.18–0.91)
|
0.028
|
Clinical History
|
|
|
|
|
Smoking
|
1.00(0.46–2.16)
|
1.000
|
1.40(0.38–5.14)
|
0.609
|
Hypertension
|
1.08(0.49–2.37)
|
0.841
|
0.38(0.08–1.85)
|
0.232
|
Diabetes mellitus
|
1.58(0.77–3.26)
|
0.212
|
1.93(0.55–6.78)
|
0.306
|
Coronary artery disease
|
1.60(0.52–4.89)
|
0.409
|
|
|
Cerebrovascular disease
|
0.50(0.05–5.51)
|
0.571
|
< 0.01(< 0.01->999)
|
0.993
|
Chronic kidney disease
|
1.33(0.56–3.16)
|
0.514
|
|
|
Hyperlipidemia
|
0.33(0.09–1.23)
|
0.099
|
|
|
Presentation feathers
|
|
|
|
|
Killip class
|
|
|
|
|
Level 1
|
Ref.
|
-
|
Ref.
|
-
|
Level 2-Level 4
|
7.75(2.74–21.96)
|
< 0.001
|
10.20(2.13–48.76)
|
0.003
|
Systolic BP (SBP)
|
0.99(0.98–0.99)
|
0.006
|
0.99(0.97-1.00)
|
0.058
|
Diastolic BP (DBP)
|
0.99(0.97–0.99)
|
0.034
|
|
|
Heart rate
|
1.00(0.99–1.01)
|
0.981
|
|
|
Peak Troponin I
|
1.05(0.99–1.10)
|
0.065
|
1.08(0.99–1.17)
|
0.056
|
Angiographic findings
|
|
|
|
|
Left main disease*
|
1.60(0.52–4.89)
|
0.409
|
4.96(0.48–51.16)
|
0.179
|
No. of disease vessels*
|
|
|
|
|
<3
|
Ref.
|
-
|
Ref.
|
-
|
≧3
|
1.83(0.68–4.96)
|
0.232
|
2.03(0.43–9.56)
|
0.370
|
Type
|
|
|
|
|
NSTEMI
|
Ref.
|
-
|
Ref.
|
-
|
STEMI
|
9.00(1.14–71.04)
|
0.037
|
> 999(< 0.01->999)
|
0.993
|
*Significant disease refers to > 75% stenosis of a coronary artery, except in left main coronary artery disease (stenosis > 50%).
NSTEMI: non-ST-elevation myocardial infarction; STEMI: ST-elevation myocardial infarction.