Population characteristics
From June 24, 2016, through April 5, 2019, a total of 360 patients were enrolled in the study. Baseline characteristics and concomitant medication at discharge were balanced between the two groups, except for the proportion of beta-blocker prescription (Table 1). All patients were prescribed LLT; of those, 304 (84.4%) were given a high-intensity statin. The loss to follow-up was 25 patients (7%); 17 died, and 8 withdrew the informed consent.
At 1-year follow-up, out of 278 patients with an LDL-C measurement, 131 (47.1%) had attained the LDL-C goal, whereas the respective number for the 2019 ESC/EAS Guidelines’ stricter goal was 31 (11.2%). Regarding other risk factors, 61.1% of the patients achieved the SBP target, 78.9% were non-smokers, 54.0% reported regular exercise, and 17.0% had BMI <25 kg/m2. Specifically, median LDL-C was 71.4 mg/dl (IQR, 57.0–93.0), SBP was 125.0 mmHg (IQR, 120.0–135.0) and BMI was 28.4 kg/m2 (IQR, 26.0–30.9).
Table 1. Patients’ characteristics at baseline grouped by treatment arm.
Characteristic
|
Overall
(n=360)
|
Control
(n=180)
|
Intervention
(n=180)
|
p-value
|
Age (years)
|
62.0 (55.0–73.0)
|
63.0 (54.8–74.0)
|
61.5 (57.0–70.3)
|
0.40
|
BMI (kg/m2)
|
27.5 (25.3–30.9)
|
27.4 (25.0–30.5)
|
27.8 (25.7–30.9)
|
0.31
|
Female sex, n (%)
|
67 (19)
|
33 (18)
|
34 (19)
|
0.89
|
Risk factors
· Arterial hypertension, n (%)
· Dyslipidemia, n (%)
· Diabetes Mellitus, n (%)
· Smoking, n (%)
· Regular exercise, n (%)
|
194 (54)
135 (38)
105 (29)
186 (52)
143 (40)
|
102 (57)
60 (33)
52 (29)
90 (50)
70 (39)
|
92 (51)
75 (41)
53 (29)
96 (53)
73 (41)
|
0.20
0.12
0.91
0.52
0.75
|
History
· Established CAD, n (%)
· Previous MI, n (%)
· PAD, n (%)
· Stroke, n (%)
· Heart failure, n (%)
· Family history of CAD, n (%)
|
100 (26)
81 (23)
35 (10)
25 (7)
58 (16)
158 (44)
|
52 (29)
42 (23)
17 (9)
12 (6)
27 (15)
78 (43)
|
48 (24)
39 (21)
18 (10)
13 (7)
31 (17)
80 (44)
|
0.24
0.52
0.85
0.76
0.60
0.83
|
Type of event
· STEMI, n (%)
· NSTEMI, n (%)
· Unstable angina, n (%)
|
199 (55)
116 (32)
45 (13)
|
104 (58)
53 (30)
23 (13)
|
95 (53)
63 (34)
22 (12)
|
0.42
0.33
0.86
|
Cholesterol (mg/dl)
· Total
· Triglycerides
· HDL
· LDL
· Non-HDL
|
171 (145–202)
130 (95–178)
38 (32–46)
102 (79–128)
132 (103–160)
|
170 (145–201)
130 (94–180)
37 (30–46)
102 (79–124)
132 (103–162)
|
171 (146–202)
130 (96–177)
38 (30–46)
104 (80–128)
132 (104–159)
|
0.69
0.90
0.30
0.68
0.95
|
eGFR (mL·min-1·1.73m2)1
|
83 (66–96)
|
82 (65–94)
|
85 (69–97)
|
0.25
|
High-sensitivity troponin (max) (ng/l)
|
1236 (248–3686)
|
1266 (241–3764)
|
1172 (284–3491)
|
0.69
|
NT-proBNP (pg/mL)
|
899 (344–2324)
|
800 (344–2213)
|
1106 (355–2613)
|
0.49
|
LVEF at discharge, n (%)
|
50 (43–55)
|
50 (42–55)
|
50 (45–55)
|
0.28
|
Primary PCI, n (%)
|
289 (81)
|
143 (81)
|
146 (82)
|
0.68
|
Conservative treatment, n (%)
|
71 (19)
|
36 (20)
|
34 (18)
|
0.64
|
Total length of hospitalization
|
8.0 (6.8–10.0)
|
8.0 (7.0–10.0)
|
7.0 (6.0–9.0)
|
0.06
|
Medication at discharge
· Statin, n (%)
· High intensity, n (%)
· Ezetimibe, n (%)
· Antiplatelet, n (%)
· ACE inhibitor, n (%)
· ARB, n (%)
· Beta-blocker, n (%)
|
351 (98)
304 (84)
39 (11)
359 (100)
160 (46)
58 (16)
309 (89)
|
174 (97)
150 (83)
20 (11)
179 (100)
83 (47)
30 (17)
146 (85)
|
177 (98)
154 (85)
19 (11)
180 (100)
77 (44)
28 (16)
163 (93)
|
0.68
0.58
0.96
0.85
0.58
0.70
0.03*
|
BMI, Body Mass Index; CAD, Coronary artery disease; MI, Myocardial infarction; PAD, Peripheral arterial disease; STEMI, ST-elevation MI; NSTEMI, non-ST-elevation MI; HDL, High-density cholesterol, LDL, Low-density cholesterol; eGFR, estimated glomerular filtration rate; NT-proBNP, N-terminal pro-b-type natriuretic peptide; LVEF, left ventricular ejection fraction; PCI, Percutaneous coronary intervention; ARB, Angiotensin II receptor blocker; ACE, Angiotensin-converting enzyme; Data were reported as absolute frequencies for discrete variables and medians (IQR) for continuous variables.1(CKD-EPI)
Adherence and LDL-C goal achievement rates
At 1-year follow-up, the median PDC was 0.92 (IQR, 0.82–1.00) in the intervention group and 0.86 (0.62–0.98) in the control group (p=0.03) (Figure 1A). In the intervention group, 126 out of 167 patients (75.5%) had good adherence compared with 111 out of 168 patients (66.1%) in the control group (adjusted odds ratio 1.76, 95% CI 1.02 to 2.62; p=0.04). However, the LDL-C goal achievement rates did not differ between the two groups neither according to the 2016 Guidelines (49.6% in the intervention group vs. 44.9% in the controls; p=0.49) (Figure 1B) nor according to the 2019 ESC Guidelines (10.1% vs. 12.3%; p=0.76). Median LDL-C values were similar between the intervention and the control group at 1-year follow-up [70 mg/dl (IQR, 56.4 – 93.0) vs. 73 mg/dl (58.0 – 92.8); p=0.55]. No significant differences between the two arms were found for the mean change from baseline LDL-C and for all other cholesterol values (Table 2). Achievement rates for other risk factors, namely smoking cessation, SBP, and BMI were also similar among the two groups (Supplementary material Table S2). Besides, self-reported medication adherence was similar between the two groups (mean 97% in the intervention vs. 96% in the control group; p=0.73).
Table 2. Goal achievements and laboratory values of the patients at 1-year follow-up.
Characteristic
|
Control
(n=138)
|
Intervention
(n = 140)
|
p-value
|
LDL-C (mg/dl)
|
73 (58.0–92.8)
|
70 (56.4–93.0)
|
0.55
|
Mean LDL-C change (mg/dl)
|
-30.2±42.6
|
-27.5±36.7
|
0.57
|
HDL-C (mg/dl)
|
41.5 (35.0–49.3)
|
42.5 (35.0–52.0)
|
0.37
|
Non-HDL-C (mg/dl)
|
98.0 (81.8–116.3)
|
92.0 (80.0–117.0)
|
0.56
|
Triglycerides (mg/dl)
|
112.5 (88.5–145.5)
|
121.0 (88.0–163.5)
|
0.33
|
Total cholesterol (mg/dl)
|
141.0 (126.0–159.0)
|
139.0 (125.0–169.0)
|
0.95
|
SBP (mmHg)
|
126.0 (121.0–136.0)
|
124.0 (119.0–134.0)
|
0.72
|
LDL, Low-density lipoprotein; C, Cholesterol; HDL, High-density lipoprotein, SBP, Systolic blood pressure; Data were reported as absolute frequencies for discrete variables and means ±SD or medians (IQR) for continuous variable
In our total population, patients with good adherence had greater mean LDL-C change from baseline [32.8±40.4 mg/dl vs. 19.8±38.1 mg/dl; p=0.02], lower LDL-C values [median 69.0 mg/dl (IQR, 55.5–88.5) vs. 80.0 mg/dl (64.0–109.0); p=0.004] (Figure 2A) than those with poor adherence and were more likely to achieve the LDL-C goal (adjusted odds ratio 1.91, 95% CI 1.09 to 3.41; p=0.02). Figure 2B shows that adherence was inversely related to mean LDL-C change from baseline for both experimental arms. Concerning the LLT at 1-year follow-up, 324 patients (96.7%) were under LLT, particularly, 323 (96.4%) were treated with statins; of those, 234 (72.4%) were on a high-intensity statin while 57 (17.6%) were taking a combination with ezetimibe.
Clinical outcomes
Our cohort’s cumulative incidence of all-cause mortality was 4.8% (95% CI 2.5 to 6.9), and 3P-MACE was 11.2% (95% CI 8.0 to 14.8) at one year following the index ACS event. In total, 37 patients (11.2%) experienced a 3P-MACE; CV death occurred in 12 patients (3.7%), nonfatal MI in 24 (7.3%), non-fatal stroke in 1 (0.3%). Besides, seven patients (2.1%) were hospitalized for heart failure. Kaplan-Meier analyses of death from any cause and 3P-MACE grouped by assigned arm are demonstrated in Figure 3. Event rates for all-cause mortality and the composite outcome were similar between the two arms [hazard ratio (HR), 1.13; 95% CI 0.4 to 2.9; p=0.8 and HR, 1.1; 95% CI 0.5 to 1.7; p=0.8, respectively]. Concerning the safety outcomes, two patients had major bleeding (one in the intervention and one in the control group). Of the patients receiving LLT, six patients (1.8%) complained of myalgias, and three of them discontinued statin therapy. No significant difference in safety outcomes was observed between the two groups.
In the univariate analysis for 3P-MACE predictors, age, history of arterial hypertension, polyvascular disease, established CAD before the index event, and eGFR<30 ml/min/1.73m2 at baseline had prognostic value for a subsequent 3P-MACE during the first year. Of note, in the multivariate analysis, only the history of arterial hypertension remained a statistically significant predictor, as shown in Table 3.
Table 3. Risk factors and goal achievement related to 3P-MACE.
Risk factors
|
Univariate analysis
|
Multivariate analysis
|
|
OR (95% CI)
|
P-Value
|
Adjusted OR (95% CI)
|
P-Value
|
Age1
|
1.02 (0.99–1.05)
|
0.13
|
1.02 (0.97–1.03)
|
0.92
|
Female
|
1.24 (0.81–2.72)
|
0.59
|
Established CAD
|
1.94 (1.01–3.71)
|
0.04*
|
1.37 (0.69–2.74)
|
0.37
|
Polyvascular disease
|
2.08 (1.00–4.29)
|
0.04*
|
1.48 (0.68–3.21)
|
0.32
|
Arterial Hypertension
|
2.93 (1.34–6.42)
|
0.007**
|
2.48 (1.07– 5.77)
|
0.03*
|
Diabetes
|
1.26 (0.63–2.50)
|
0.5
|
eGFR<30 ml/min/1.73m2
|
3.36 (1.19–9.50)
|
0.02*
|
5.49 (1.80–16.69)
|
0.16
|
Increased NT-proBNP2
|
1.62 (0.49–5.3)
|
0.40
|
LDL-C <70 mg/dl
|
1.43 (0.57–3.57)
|
0.43
|
OR, Odds ratio; CI; Confidence interval; CAD, Coronary artery disease; eGFR, estimated glomerular filtration rate; NT-proBNP, N-terminal pro-b-type natriuretic peptide; LDL-C, Low-density lipoprotein cholesterol;
1continuous variable;
2Age>75 and nt-proBNP>450pg/ml or age<75 and nt-proBNP>125pg/ml