3.1 Patient population and Performance measure (Quality of care)
During the whole study period, a total of 1083 AMI patients with 459 of STEMI (42.4%) or 624 of NSTEMI (57.6%) were enrolled. 54 patients died before discharge, therefore, the analysis of prescription of discharge guideline recommended medications were estimated with 1029 patients. 108 AMI patients died within six months after admission, so 975 patients were taken into account for 6-month physician adherence assessment. Finally, totally 149 patients cumulatively died during the one-year period post admission as AMI in our registry.
Overall, physician adherence rates for the key performance measures (discharge medication)were: 94.8% for aspirin, 54.2% for clopidogrel, 64.5% for beta-blockers, 61.4% for ACEI/ARBs use in patients with LVSD, 83.5% for statins.
For secondary prevention adherence at 6-month: calculated by the type of AMI, the STEMI population had a significantly higher usage than NSTEMI of aspirin (94.8% vs. 91.4%, P = 0.042), ACEI/ARBs (67.6% vs. 58.8%, P = 0.006), statins (90.3% vs. 81.5%, P < 0.001) and all 5 medications (21.1% vs.14.4%, P = 0.012).
Table 1 showed the baseline clinical characteristics of two different discharge prescription patterns (active vs. passive). Additionally, this pattern of active prescription was seen in those lower risk patients (who were younger, with less comorbidities, had better LVEF value) and who were treated more aggressively with secondary prevention on discharge. However, for clopidogrel, the discharge medication pattern was highly associated with the patients’ vascular histories and in-hospital percutaneous coronary intervention (PCI) treatment.
Table 1
Baseline characteristics & intervention therapy of active and passive prescription patterns
|
Aspirin
|
P value
|
Clopidogrel
|
P value
|
Beta-blocker
|
P value
|
ACEI/ARBs
|
P value
|
Statins
|
P value
|
Prescription Pattern
|
Active
|
Passive
|
|
Active
|
Passive
|
|
Active
|
Passive
|
|
Active
|
Passive
|
|
Active
|
Passive
|
|
Number
|
652
|
307
|
|
542
|
16
|
|
392
|
249
|
|
393
|
215
|
|
545
|
219
|
|
Demographics
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Age, mean(SD)
|
66.2 ± 12.7
|
73.4 ± 1.3
|
< 0.001
|
64.7 ± 11.8
|
66.0 ± 14.4
|
0.657
|
66.5 ± 13.3
|
70.9 ± 11.3
|
< 0.001
|
67.8 ± 13.3
|
70.2 ± 11.2
|
0.018
|
66.2 ± 12.8
|
70.1 ± 11.2
|
< 0.001
|
Male, no.%
|
71.9
|
61.6
|
0.001
|
75.5
|
87.5
|
0.268
|
70.9
|
60.6
|
0.007
|
73.5
|
63.3
|
0.008
|
72.8
|
63.9
|
0.015
|
Smoker, no.%
|
51.7
|
42.0
|
0.005
|
54.1
|
56.2
|
0.862
|
50.3
|
39.8
|
0.009
|
53.7
|
43.7
|
0.019
|
53.2
|
45.2
|
0.045
|
Medical histories, no.%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
MI
|
2.5
|
29.0
|
< 0.001
|
7.9
|
43.8
|
< 0.001
|
3.1
|
21.7
|
< 0.001
|
6.6
|
21.4
|
< 0.001
|
3.1
|
27.4
|
< 0.001
|
PVD
|
0.9
|
3.3
|
0.008
|
0.6
|
12.5
|
< 0.001
|
1.3
|
1.6
|
0.729
|
1.8
|
2.3
|
0.645
|
0.6
|
3.2
|
0.004
|
Stroke
|
2.0
|
22.5
|
< 0.001
|
5.0
|
25.0-
|
0.001
|
7.4
|
11.2
|
0.095
|
5.6
|
14.0
|
< 0.001
|
4.2
|
16.0
|
< 0.001
|
Diabetes mellitus
|
26.8
|
49.8
|
< 0.001
|
28.2
|
43.8
|
0.176
|
29.3
|
48.6
|
< 0.001
|
26.2
|
58.6
|
< 0.001
|
26.2
|
48.4
|
< 0.001
|
Hypertension
|
52.0
|
73.3
|
< 0.001
|
54.6
|
43.8
|
0.390
|
54.8
|
81.5
|
< 0.001
|
54.2
|
81.4
|
< 0.001
|
53.6
|
71.2
|
< 0.001
|
Hyperlipidemia
|
21.9
|
34.5
|
< 0.001
|
25.3
|
18.8
|
0.553
|
23.0
|
34.5
|
0.001
|
21.6
|
34.9
|
< 0.001
|
16.5
|
57.5
|
< 0.001
|
CRF
|
4.3
|
20.2
|
< 0.001
|
5.4
|
6.2
|
0.875
|
5.6
|
19.7
|
< 0.001
|
3.6
|
15.3
|
< 0.001
|
4.2
|
18.7
|
< 0.001
|
CHF
|
2.8
|
19.5
|
< 0.001
|
3.9
|
25.0
|
< 0.001
|
4.6
|
14.1
|
< 0.001
|
5.1
|
15.8
|
< 0.001
|
5.0
|
13.7
|
< 0.001
|
Physical characteristics at admission
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Heart rate (bpm), mean(SD)
|
79.7 ± 20.9
|
85.6 ± 21.6
|
< 0.001
|
79.1 ± 19.0
|
96.2 ± 23.9
|
0.002
|
84.2 ± 20.1
|
81.9 ± 21.0
|
0.186
|
82.4 ± 22.4
|
83.8 ± 20.9
|
0.486
|
80.6 ± 20.3
|
83.1 ± 21.4
|
0.139
|
SBP (mmHg), mean(SD)
|
141.6 ± 30.1
|
148.5 ± 33.0
|
0.003
|
29.2 ± 1.3
|
30.7 ± 8.5
|
0.580
|
147.3 ± 28.1
|
150.6 ± 33.1
|
0.196
|
145.1 ± 30.2
|
151.4 ± 33.9
|
0.028
|
144.3 ± 29.8
|
145.7 ± 35.2
|
0.583
|
LVEF(%), mean(SD)
|
51.6 ± 12.1
|
49.2 ± 13.9
|
0.039
|
11.7 ± 0.6
|
17.8 ± 6.7
|
0.224
|
11.7 ± 0.70
|
13.2 ± 1.0
|
0.418
|
50.1 ± 12.4
|
51.2 ± 13.9
|
0.416
|
51.0 ± 12.2
|
50.5 ± 13.8
|
0.639
|
Killip class III–IV, no.%
|
8.1
|
11.7
|
0.073
|
5.7
|
6.2
|
0.928
|
|
|
|
7.1
|
9.8
|
0.252
|
6.2
|
11.4
|
0.015
|
STEMI, no.%
|
50.6
|
22.8
|
< 0.001
|
51.7
|
25.0
|
0.036
|
42.9
|
29.7
|
0.001
|
50.6
|
30.2
|
< 0.001
|
51.0
|
28.3
|
< 0.001
|
Laboratory results, mean (SD)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Serum LDL (mmol/L)
|
3.1 ± 1.0
|
2.4 ± 1.0
|
< 0.001
|
3.0 ± 1.0
|
1.8 ± 0.8
|
< 0.001
|
3.1 ± 1.0
|
2.6 ± 1.1
|
< 0.001
|
2.9 ± 1.0
|
2.6 ± 1.0
|
< 0.001
|
3.2 ± 1.0
|
2.4 ± 1.1
|
< 0.001
|
eGFR, mL/min/1.73 m2
|
65.2 ± 25.3
|
49.6 ± 13.9
|
< 0.001
|
64.9 ± 21.8
|
72.5 ± 35.3
|
0.408
|
65.1 ± 22.9
|
50.6 ± 26.5
|
< 0.001
|
51.3 ± 25.9
|
50.1 ± 12.4
|
< 0.001
|
65.4 ± 25.0
|
52.6 ± 26.1
|
< 0.001
|
In-hospital Treatment
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PCI, no.%
|
63.3
|
38.8
|
< 0.001
|
89.1
|
56.2
|
< 0.001
|
61.0
|
45.4
|
< 0.001
|
60.8
|
47.0
|
0.001
|
65.5
|
48.9
|
< 0.001
|
*All the data used in analyzing were after adjusted with excluding the patients who have contraindications. |
ACEI/ARBs, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARB); CI, confidence interval; OR, Odds ratio; STEMI, ST elevated myocardial infarction; eGFR, estimated glomerular filtration rate; CHF: congestive heart failure; CRF, chronic renal failure; MI, myocardial infarction; PVD, peripheral vascular disease; PCI, percutaneous coronary intervention; LDL, low-density lipoprotein; LVEF, left ventricular ejection fraction; SBP, systolic blood pressure |
3.2 Predictors of adherence to guideline therapy
3.2.1 Discharge prescription
As shown in Table 2 increasing age was related to the lower prescription rates of aspirin (OR = 0.94; 95% CI = 0.91–0.97; P = 0.001, per year), beta-blockers (OR = 0.97; 95% CI = 0.96–0.99; P < 0.001, per year) and statins (OR = 0.95; 95% CI = 0.94–0.97; P < 0.001, per year) on discharge. Traditional risk features (corresponding medical histories and comorbidities) were correlated with lower usage of beta-blockers and ACEI/ARBs, but did not significantly influence the prescription rate of aspirin and statins on discharge.
Table 2
Predictors of adherence to discharged &6-month medical therapy
|
Adjusted OR
|
95% CI
|
P value
|
Aspirin on discharge
|
|
|
|
Age (per year)
|
0.94
|
0.91–0.97
|
0.001
|
Index revascularization
|
2.77
|
1.13–6.82
|
0.026
|
Aspirin before admission
|
4.84
|
1.90–12.30
|
0.001
|
Clopidogrel on discharge
|
|
|
|
eGFR( mL/min/1.73 m2)
|
1.01
|
1.00-1.02
|
0.037
|
Hemoglobin(g/dL)
|
1.17
|
1.05–1.29
|
0.004
|
Killip class (III-IV)
|
0.45
|
0.23–0.86
|
0.016
|
Index revascularization
|
34.28
|
22.94–51.22
|
< 0.001
|
Beta-blockers on discharge
|
|
|
|
Age (per year)
|
0.97
|
0.96–0.99
|
< 0.001
|
NSTEMI
|
1.54
|
1.18–2.02
|
0.002
|
History of Hypertension
|
1.75
|
1.31–2.32
|
< 0.001
|
Heart Failure on admission
|
0.58
|
0.35–0.95
|
0.032
|
Beta-blockers before admission
|
2.50
|
1.83–3.42
|
< 0.001
|
ACEI/ARBs on discharge
|
|
|
|
Systolic Blood Pressure
(per mmHg)
|
1.01
|
1.00-1.02
|
< 0.001
|
Diabetes mellitus
|
1.43
|
1.03–1.98
|
0.033
|
ACEI/ARBs before admission
|
2.93
|
1.97–4.34
|
< 0.001
|
Statins on discharge
|
|
|
|
Age (per year)
|
0.95
|
0.94–0.97
|
< 0.001
|
STEMI
|
1.94
|
1.32–2.87
|
0.001
|
Albumin (per g/l)
|
1.08
|
1.04–1.12
|
< 0.001
|
Peak Creatinine (per µmol/l)
|
0.99
|
0.98–1.01
|
0.018
|
Statins before admission
|
8.27
|
0.35–15.71
|
< 0.001
|
Combined medication use on discharge
|
|
|
|
Diastolic Blood Pressure
(per mmHg)
|
1.01
|
1.00-1.03
|
0.005
|
Index revascularization
|
9.6
|
5.60–16.5
|
< 0.001
|
ACEI/ARBs before admission
|
1.92
|
1.26–2.92
|
0.003
|
Aspirin at 6-month
|
|
|
|
Index revascularization
|
1.97
|
1.08–3.58
|
0.027
|
Aspirin on discharge
|
15.13
|
7.13–32.13
|
< 0.001
|
Clopidogrel at 6-month
|
|
|
|
Albumin during hospitalization (g/L)
|
1.05
|
1.01–1.09
|
0.018
|
History of revascularization
|
2.04
|
1.15–3.63
|
0.015
|
Index revascularization
|
2.51
|
1.45–4.35
|
0.001
|
Clopidogrel on discharge
|
6.02
|
3.42–10.60
|
< 0.001
|
Beta-blockers at 6-month
|
|
|
|
Current smoker
|
0.54
|
0.34–0.85
|
0.008
|
Heart rate during hospitalization (bpm)
|
1.01
|
1.00-1.02
|
0.029
|
Albumin during hospitalization (g/L)
|
1.04
|
1.01–1.08
|
0.047
|
Beta-blockers on discharge
|
19.70
|
13.00-29.85
|
< 0.001
|
ACEI/ARBs at 6-month
|
|
|
|
Hypertension
|
1.51
|
1.01–2.26
|
0.044
|
CHF
|
2.27
|
1.32–3.91
|
0.003
|
AF
|
0.274
|
0.09–0.87
|
0.029
|
Presented with STEMI
|
1.92
|
1.28–2.89
|
0.002
|
ACEI/ARBs on discharge
|
15.43
|
10.36–22.98
|
< 0.001
|
Statins at 6-month
|
|
|
|
Statins on discharge
|
26.30
|
15.90-43.51
|
< 0.001
|
Combined medication use
at 6-month
|
|
|
|
History of revascularization
|
1.97
|
1.09–3.53
|
0.024
|
Index revascularization
|
2.80
|
1.59–4.93
|
< 0.001
|
Statins on discharge
|
8.24
|
5.35–12.70
|
< 0.001
|
*All the data used in analyzing were after adjusted with excluding the patients who have contraindications. |
+Analysis performed using multivariable logistic regression, variables in the model including baseline characteristics, medical histories, medication before admission, presentation of AMI, laboratory results during hospitalization, and procedures during index admission. |
ACEI/ARBs, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARB); CI, confidence interval; OR, Odds ratio; STEMI, ST elevated myocardial infarction; NSTEMI, non- ST elevated myocardial infarction; eGFR, estimated glomerular filtration rate; CHF: congestive heart failure; AF: atrial fibrillation; Combined medication: combined using five medication including aspirin, Clopidogrel, Beta-blockers, ACEI/ARBs, and Statins |
Invasive procedures during hospitalization including PCI or coronary artery bypass grafting (CABG) were strongly associated with discharged prescription of aspirin. In-hospital revascularization was strongly associated with clopidogrel discharge prescription, as well as higher level of estimated glomerular filtration rate (eGFR) and hemoglobin during hospitalization and lower standard Killip-class (I or II). Presenting with NSTEMI and having a medical history of hypertension (HT) were associated with a higher likelihood to be discharged on beta-blockers, whereas having congestive heart failure (CHF) on admission was surprisingly a block to its use. Presenting with higher systolic blood pressure and diabetes mellitus (DM) were predictors of ACEI/ARBs prescription in eligible patients. In those diagnosed as STEMI, higher albumin level during hospitalization predicted use of statins on discharge, while lower peak creatinine level during index hospitalization was more likely to be prescribed with statins. Patients who underwent revascularization during index hospitalization were more likely to be prescribed with combined therapy on discharge (Table 2).
Patients who were not on a given medication before admission were less likely to be prescribed it on discharge and this was consistent through the four medications, except clopidogrel. Clopidogrel was highly influenced by invasive interventions like PCI or CABG. Taking a specific medication before admission was still the strongest independent predictor for it to be taken on discharge of other four drugs; aspirin before admission (OR = 4.84; 95% CI = 1.90–12.30; P = 0.001) for aspirin on discharge; beta-blockers before admission (OR = 2.50; 95% CI = 1.83–3.42; P < 0.001) for beta-blockers on discharge; ACE/ARBs before admission (OR = 2.93; 95% CI = 1.97–4.34; P < 0.001) for ACE/ARBs on discharge; statins before admission (OR = 8.27; 95% CI = 0.35–15.71; P < 0.001) for statins on discharge. And for combination guideline prescription, ACEI/ARBs used before admission played a non-ignorable role in the medical part (OR = 1.92; 95% CI = 1.26–2.92; P = 0.003) (Table 2).
3.2.2 Six-month prescription
Table 2 shows the attributes of the disparate 6-month utilization of individual recommendation and composited treatment pattern and adherence in a multivariable model.
Predictors of losing prescription at 6-month were different for each drug. For aspirin, less in-hospital revascularization including PCI or CABG and not prescribed with aspirin on discharge were found to be independent predictors. For clopidogrel, the strongest predictors associated with lower continuous use were no history of revascularization, decreasing level of albumin, no index procedure of PCI or CABG, and without clopidogrel prescription on discharge. As for beta-blockers, current smoker, less heart rate beats, lower in-hospital laboratory level of albumin, and no prescription of beta-blockers contributed to inconstant use. In terms of ACEI/ARBs, independent predictors of withheld prescription were presence of AF, absence of CHF and hypertension, presentation with NSTEMI, and not prescribed ACEI/ARBs on discharge. Inconsistent use of statins was the result of no prescription on discharge. No revascularization before admission or during hospitalization and no statin therapy on discharge were considered to be two independent factors for low prescription rate of combined medication (Table 2).
3.3 Impact of passive prescription
According to Table 3, the patients who received the prescription on discharge and did not get the same medication before admission (active prescription pattern) had the lower risk in 6-month and 1-year mortality compared with the patients who adhered to discharge guideline recommendation and already treated with the same therapy before admitted to hospital (passive prescription pattern). Specifically, for 6-month mortality post discharge, active prescription compared with passive prescription of aspirin (2.9% vs. 7.5%, P < 0.001), beta-blockers (2.3% vs. 6.8%, P = 0.005), statins (2.4% vs.5.9%, P = 0.014); for one-year mortality post discharge, active prescription comparing with passive prescription of aspirin (5.7% vs. 13.7%, P < 0.001), beta-blockers (5.6% vs. 12.9%, P = 0.001), statins (4.6% vs.11.0%, P = 0.001). Even after adjustment for age, gender, smoking status, cardiovascular disease histories, diabetes, hypertension, hyperlipidemia, and discharge diagnosis, active prescription still demonstrated survival benefit compared to passive prescription: for 6-month mortality, aspirin (OR = 0.436, 95% CI = 0.225–0.845, P = 0.014), beta-blockers (OR = 0.374, 95% CI = 0.163–0.861, P = 0.021); for 1-year mortality, aspirin (OR = 0.538, 95% CI = 0.326–0.887, P = 0.015), beta-blockers (OR = 0.481, 95% CI = 0.260–0.892, P = 0. 020), statins (OR = 0.514, 95% CI = 0.277–0.956, P = 0.036).
Table 3
Impact of passive prescription on 6-month &1-year mortality post discharge
Variables
|
Prescription
Pattern
|
6-month
mortality
|
|
Adjusted# OR of 6-month
mortality
|
1-year
mortality
|
|
Adjusted# OR of 1-year
mortality
|
|
|
No.%
|
P value
|
OR
|
95%CI
|
P value
|
No.%
|
P value
|
OR
|
95%CI
|
P value
|
Aspirin
|
Active
|
2.9%
|
< 0.001
|
0.436
|
0.225–0.845
|
0.014
|
5.7%
|
< 0.001
|
0.538
|
0.326–0.887
|
0.015
|
|
Passive
|
7.5%
|
|
1.000
|
Reference
|
|
13.7%
|
|
1.000
|
Reference
|
|
Clopidogrel
|
Active
|
0.0%
|
0.730
|
-------
|
-------
|
-------
|
0.0%
|
0.547
|
-------
|
-------
|
-------
|
|
Passive
|
0.7%
|
|
-------
|
-------
|
-------
|
2.2%
|
|
-------
|
-------
|
-------
|
Beta-Blockers
|
Active
|
2.3%
|
0.005
|
0.374
|
0.163–0.861
|
0.021
|
5.6%
|
0.001
|
0.481
|
0.260–0.892
|
0.020
|
|
Passive
|
6.8%
|
|
1.000
|
Reference
|
|
12.9%
|
|
1.000
|
Reference
|
|
ACEI/ ARBs
|
Active
|
4.8%
|
0.919
|
-------
|
-------
|
-------
|
6.9%
|
0.283
|
-------
|
-------
|
-------
|
|
Passive
|
4.7%
|
|
-------
|
-------
|
-------
|
9.3%
|
|
-------
|
-------
|
-------
|
Statins
|
Active
|
2.4%
|
0.014
|
0.538
|
0.326–0.887
|
0.125
|
4.6%
|
0.001
|
0.514
|
0.277–0.956
|
0.036
|
|
Passive
|
5.9%
|
|
1.000
|
Reference
|
|
11.0%
|
|
1.000
|
Reference
|
|
ACEI/ARBs, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARB), odds ratio (OR) |
*All the data used in analyzing were after adjusted for age, gender, cardiovascular medical histories, diabetes, hypertension, hyperlipidemia, smoking status, discharge diagnosis. |
In Kaplan–Meier survival analysis, active prescription of aspirin had the better one year survival rate (Log-rank χ2 = 17.8, P < 0.001), active prescription of beta-blockers also gave significant benefit in one year survival rate (Log-rank χ2 = 10.3, P = 0.001), as well as the active use of statins (Log-rank χ2 = 10.7, P = 0.001) (Fig. 1). After adjustment with age, gender, smoking status, cardiovascular disease histories, diabetes, hypertension, hyperlipidemia and, discharge diagnosis, the hazard ratio (HR) of active prescription of aspirin was [HR = 1.750, 95% CI = 1.091–2.805, P = 0.020], of beta-blockers was [HR = 1.955, 95% CI = 1.099–3.477, P = 0.022], of statins was [HR = 1.891, 95% CI = 1.056–3.388, P = 0.032].