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Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome
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Original article
Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome Yuttana Wongsalap (PharmD)a, Arom Jedsadayanmata (PharmD PhD)b,c,d,* a
School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand c Drug Information and Consumer Protection Center, Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand d Center of Excellence in Pharmacy Practice and Management Research, Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 June 2019 Received in revised form 5 August 2019 Accepted 13 August 2019 Available online xxx
Background: Previous studies on the use of high-intensity statins and low-density lipoprotein cholesterol (LDL-C) goal achievement were mostly conducted in patients with acute coronary syndrome (ACS) receiving care before 2013. We aimed to determine trends and predictors of high-intensity statin therapy and LDL-C goal achievement in a more recent cohort of Thai ACS patients. Methods: We analyzed data from electronic databases of ACS patients at a tertiary-care, teaching hospital in Thailand between 2013 and 2017. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement after hospital discharge were determined with logistic regression analysis. Results: Among 1753 ACS patients, 987 (56.3%) received high-intensity statin at discharge. A higher proportion of ACS patients were prescribed high-intensity statins over time (p = 0.033 for linear trend), rising from 10% in 2013 to 88% in 2017. Independent predictors of high-intensity statin therapy included age 75 years, a diagnosis of myocardial infarction, receiving P2Y12 inhibitors, and beta-blockers. Within 120 days after discharge, 427 (24.4%) patients had follow-up LDL-C measurements. Overall, 185 (43.3%) patients achieved LDL-C goals based on either of the following criteria: LDL-C <70 mg/dL or 50% reduction in the baseline LDL-C. There was a non-significant trend (p = 0.402 for linear trend) in the proportion of patients achieving LDL-C goals over the study period. Independent predictors of achieving LDL-C goal included high-intensity statin therapy after discharge and lower baseline LDL-C on admission. Conclusions: In a more recent cohort of Thai ACS patients, a higher proportion of patients were prescribed high-intensity statins before discharge over the study period. However, the proportion of patients who achieved LDL-C goal did not increase accordingly. This finding should promote more discussion among health policy makers to improve statin treatment and quality of care for ACS patients. © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Acute coronary syndrome Goal achievement Intensity Low-density lipoprotein cholesterol Statin Predictor Trend
Introduction The elevated level of low-density lipoprotein cholesterol (LDLC) has been recognized as an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Lowering LDL-C with statins reduces adverse cardiovascular events in patients with or without established ASCVD [1,2]. The American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol emphasizes initiating statin therapy at the appropriate intensity based on patient’s ASCVD risk [3].
* Corresponding author at: Faculty of Pharmacy, Thammasat University, Khong Luang, Pathum Thani 12120, Thailand. E-mail address: [email protected] (A. Jedsadayanmata).
While the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guideline underscores the achievement of LDL-C target based on ASCVD risk [4]. Patients with acute coronary syndrome (ACS) are at heightened risk of cardiovascular events [3,4]. Studies have shown that statin therapy significantly reduces these cardiovascular events among ACS patients, particularly when started early after the events [5–7]. Further, a more intensive statin therapy has proved to be more efficacious than the lower intensity [5–7]. Despite the evidence of the potential benefits of high-intensity statins, previous studies using real-world data indicated that the intensity of statin therapy was suboptimal and the LDL-C goal achievement remained low among ACS patients [8–14]. Of note, however, most of these studies were conducted with a patient cohort receiving care before 2013, and thus the results may not reflect clinical practice on blood
https://doi.org/10.1016/j.jjcc.2019.08.012 0914-5087/© 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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cholesterol management after the release of more recent guidelines by ACC/AHA and ESC/EAS [3,4]. In the present study, by recruiting a more recent cohort of Thai ACS patients between 2013 and 2017, we aimed to determine temporal trends and predictors of high-intensity statin therapy and the LDL-C goal achievement among ACS patients discharged with statins. The results will provide more updated information to improve quality of care for ACS patients.
based on the following criteria: (1) an achievement of 50% reduction in LDL-C level from baseline, (2) an attainment of LDL-C level <70 mg/dL, and (3) either of the criteria in (1) or (2). The 120day after discharge was chosen as the time point to determine goal achievement based on the study showing that most ACS patients achieved goal within 120 days after discharge if they were going to achieve LDL-C goals [15]. Statistical analysis
Methods Study population and setting We retrospectively reviewed data of the ACS patients who were admitted to a 1000-bed, tertiary-care, teaching hospital in Phitsanulok province located in northern Thailand. The hospital served as a referral-center for advanced and interventional cardiovascular care in the lower northern region of Thailand. Patient data were retrieved from electronic medical and administrative claims database at the study hospital. Patients were eligible for recruitment if they were 18 years of age or older and hospitalized with ACS between January 1, 2013, and November 30, 2017. ACS was defined as a ST-segment elevation myocardial infarction (STEMI), a non-ST-segment elevation myocardial infarction (NSTEMI), or unstable angina (UA). Eligible ACS patients were identified with the ICD-10 (International Statistical Classification of Diseases and Related Health Problems, 10th Revision) diagnosis codes of I20.0 (UA) and I21.x (acute MI). Other eligible criteria included having a lipid profile drawn within 24 h after hospitalization, no record of statin therapy at least 6 months prior to admission, and were prescribed statin therapy before hospital discharge. Patients were excluded if they did not survive until hospital discharge or were transferred to other hospitals for further management. The study protocol received an ethical approval by the Institutional Review Board on Human Research at the study hospital prior to data collection. The informed consent from patients was not required. Data collection The electronic medical and claims database were all linked by the patient unique identification number. The claims database provided information on patient demographics, health insurance status, principal diagnoses at index hospitalization, comorbidities, interventions, and medications received during hospitalization and at outpatient visits. Comorbidities were identified with the ICD-10. Interventions, e.g. a revascularization procedure, were identified using ICD-9 CM (The International Classification of Diseases, 9th Revision, Clinical Modification). The medical database was reviewed to retrieve information on smoking status, the family history of coronary heart disease (CHD), and the confirmation of no statin use prior to admission. Statin therapy at hospital discharge was identified through the electronic claims database. Statins available at the study hospital included atorvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. Statin intensity was defined in accordance with the 2013 ACC/AHA blood cholesterol guideline [3]. High-intensity statin therapy consisted of atorvastatin prescribed at 40 or 80 mg daily, rosuvastatin at 20 or 40 mg daily, and simvastatin at 80 mg daily. The rest of statin therapy not aforementioned were considered as a low-to-moderate intensity. The lipid profiles were available from electronic reports of the central laboratory department and were linked to other patient data by the patient unique identification number. We defined the LDL-C goal achievement within 120 days after hospital discharge
Baseline characteristics were summarized and presented as frequency and proportions (percentage) for categorical variables. Numeric variables were summarized as means and standard deviations (SDs). To determine the proportion of patients receiving highintensity statins or achieving LDL-C goal, we stratified patients by years of recruitment into the study and calculated the proportion of patients receiving high-intensity statins or achieving LDL-C goal by dividing the total number of patients receiving highintensity statins or achieving LDL-C goal (nominators) with the total number of ACS patients (denominators) within that year. A time trend analysis was performed by unadjusted logistic regression as described previously [16,17]. The model was constructed with the proportion of patients who received highintensity statins or achieved LDL-C goal stratified by years of recruitment as dependent variables and time (years) from 1 to 5 as independent variables as follows: LnðEðn=NÞÞ ¼ constant þ b Year where n denotes an estimated number of patients receiving highintensity statins or achieving LDL-C goal in each year, and N denotes the total number of patients in the same year, and Year denotes a categorical variable from 1 to 5 for the respective years between 2013 and 2017. To identify predictors of receiving high-intensity statins or achieving LDL-C goal, we categorized patients into 2 groups either by the statin intensity (high vs. low/moderate) or the achievement of LDL-C goal (achieved vs. not achieved). The baseline characteristics between groups were compared, using chi-square or Fisher’s exact test as appropriate for categorical variables, and independent t-test for numeric variables. Potential predictors were identified as baseline variables with a p-value of <0.2 in the univariable analysis, and were all entered into multivariable logistic regression to identify independent predictors of high-intensity statin therapy or achieving LDL-C goal accordingly. All statistical analyses were performed two-sided, with a pvalue of <0.05 considered as statistically significant. All statistical analyses were performed using Stata software (StataCorp LLC, College Station, TX, USA). Results Intensity of statin therapy A total of 4447 patients hospitalized with ACS between 2013 and 2017 were identified. Among them, 2739 (96%) were prescribed statins at hospital discharge. Patients who had documented use of statins prior to admission or had no LDL-C level drawn within 24 h after admission were excluded. The remaining 1753 patients were recruited into this study (Fig. 1). Overall, 987 (56.3%) patients were prescribed high-intensity statins over a 5-year period (Table 1). The remaining 766 (43.7%) patients received statins at the low-to-moderate intensity prior to discharge. The prescribed statins included atorvastatin 80 mg daily (n = 5), atorvastatin 40 mg daily (n = 980), and rosuvastatin 20 mg daily (n = 2). Less than 1% of patients were prescribed non-statin
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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Fig. 1. Patient flow chart. ACS, acute coronary syndrome; LDL-C, low-density lipoprotein cholesterol.
therapy. When categorizing patients by years of hospitalization, we observed a noticeably rise in the proportions of ACS patients who were prescribed high-intensity statins after 2013. In 2013, 10% of the cohort were prescribed high-intensity statins, but the proportions increased to 32% and 88% in 2014 and 2016, respectively. A significant linear trend (p = 0.033 for trend) in the increased proportion of patients receiving high-intensity statins over the 5-year period was observed (Table 1). Table 2 shows baseline characteristics of the entire ACS patients in this study. The mean age was 67.9 12.4 years, and 63% of them were male. Ninety percent of the cohort were diagnosed with NSTEMI (47.8%) or STEMI (43.1%), and 62.9% had undergone PCI during the index hospitalization. Table 2 also compares characteristics of the patients who were prescribed high-versus low-tomoderate-intensity statins. Patients with the following characteristics were more likely to receive high-intensity statins before discharge: being 75 years of age, male gender, current smokers, a higher baseline LDL-C on admission, having undergone percuta-
Table 1 Trend in the proportion of patients who were prescribed high-intensity statins before discharge between 2013 and 2017. Years
Total patients
n (%)
p-value for trend
2013 2014 2015 2016 2017 Total
340 405 408 319 281 1753
34 (10.0) 130 (32.1) 293 (71.8) 281 (88.1) 249 (88.6) 987 (56.3)
.033
neous coronary intervention (PCI), receiving P2Y12 inhibitors or
b-blockers before discharge.
Multivariable logistic regression identified independent predictors of high-intensity statin treatment (Table 3). Age 75 years, having diagnosis of MI in comparison to unstable angina, the LDL-C level > 100 mg/dL on admission, having undergone PCI, receiving P2Y12 inhibitors or beta-blockers at discharge all increased the likelihood of receiving high-intensity statin therapy independently of other factors. LDL-C goal achievement We define LDL-C goal achievement by the criteria described under the Methods section. Table 4 shows the proportion of ACS patients who achieved LDL-C goal within 120 days after discharge according to the years of patient recruitment over a 5-year period. Overall, 23.2% of patients achieved 50% reduction in LDL-C, but a higher proportion (35.1%) achieved the LDL-C level <70 mg/dL. Based on either of the criteria, 185 (43.4%) were considered to achieve the LDL-C goal. We observed the highest proportion (55%) of patients achieving LDL-C goal in the year 2015, but the proportions declined in 2016 and 2017. There was a non-significant linear trend (p = 0.402) in the proportion of patients achieving LDL-C goal over the 5-year period. Table 5 compares characteristics of ACS patients who achieved versus did not achieve LDL-C goal at 120 days after discharge. Patients who had a lower baseline LDL-C on admission and received high-intensity statins before discharge were more likely to achieve LDL-C goals within 120 days. Multivariable analysis identified a higher baseline LDL-C as the negative predictor, whereas high-intensity statins as a positive predictor of LDL-C goal
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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Table 2 Characteristics of acute coronary syndrome patients according to statin intensity at discharge. Characteristics
All patients (N = 1753) n (%)
High intensity (N = 987 n (%)
Low/moderate intensity (N = 766) n (%)
p-value
Age 75 years Female Current smoker Family history of CHD Health insurance UCS CSMBS SSS Comorbidities Diabetes mellitus Hypertension History of CHD Ischemic stroke CKD stage III–V Index events Unstable angina STEMI NSTEMI Revascularization PCI CABG Lipid profiles LDL-C < 70 mg/dL LDL-C 70-100 mg/dL LDL-C > 100 mg/dL LDL-C (mean SD) (mg/dL) Number of home medications Cardiovascular medications Aspirin P2Y12 inhibitors Beta-blockers ACEI or ARB
1,238 (70.6) 644 (36.7) 470 (26.8) 25 (1.4)
781 (79.1) 319 (32.3) 298 (30.2) 17 (1.7)
457 (59.7) 325 (42.4) 172 (22.5) 8 (1.0)
<0.001 <0.001 <0.001 0.235 0.335
1304 (74.4) 353 (20.1) 96 (5.5)
721 (73.0) 208 (21.1) 58 (5.9)
583 (76.1) 145 (18.9) 38 (5.0)
452 (25.8) 682 (38.9) 10 (0.6) 15 (0.9) 103 (5.9)
263 (26.7) 358 (36.3) 3 (0.3) 9 (0.9) 46 (4.7)
189 (24.7) 324 (42.3) 7 (0.9) 6 (0.8) 57 (7.4)
160 (9.1) 756 (43.1) 837 (47.8)
55 (5.6) 478 (48.4) 454 (46.0)
105 (13.7) 278 (36.3) 383 (50.0)
1103 (62.9) 33 (1.9)
701 (71.0) 23 (2.3)
402 (52.5) 10 (1.3)
211 (12.0) 454 (25.9) 1088 (62.1) 117.1 44.9 8.4 2.2
101 (10.2) 231 (23.4) 655 (66.4) 122.0 47.4 8.5 2.2
110 (14.4) 223 (29.1) 433 (56.5) 110.9 40.6 8.3 2.3
<0.001 0.178
1672 (95.4) 1618 (92.3) 1279 (73.0) 1220 (69.6)
951 (96.4) 940 (95.2) 759 (76.9) 692 (70.1)
721 (94.1) 678 (88.5) 520 (67.9) 528 (68.9)
0.028 <0.001 <0.001 0.593
0.349 0.010 0.115 0.772 0.014 <0.001
<0.001 0.117 <0.001
ACEI, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CHD, coronary heart disease; CKD, chronic kidney disease; CSMBS, civil servant medical benefit scheme; LDL-C, low-density lipoprotein cholesterol; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; SSS, social security scheme; STEMI, ST-elevation myocardial infarction; UCS, universal coverage scheme.
Discussion
Table 3 Independent predictors of high-intensity statin therapy at discharge. Variables
Adjusted ORs
95%CI
p-value
Age 75 years Female Current smoker Hypertension Chronic IHD CKD Index event Unstable angina STEMI NSTEMI PCI CABG Lipid profiles LDL-C < 70 mg/dL LDL-C 70–100 mg/dL LDL-C > 100 mg/dL Number of home medications Aspirin P2Y12 inhibitors Beta-blockers
2.38 0.89 1.07 0.86 0.70 0.83
1.90–2.99 0.71–1.12 0.83–1.37 0.69–1.07 0.16–3.13 0.54–1.29
<0.001 0.313 0.612 0.166 0.644 0.414
Reference 2.05 2.02 1.68 1.92
1.36–3.11 1.38–2.95 1.31–2.16 0.87–4.23
0.001 <0.001 <0.001 0.104
Reference 1.05 1.39 1.05 0.73 1.63 1.41
0.75–1.49 1.02–1.91 0.99–1.10 0.42–1.26 1.03–2.58 1.11–1.79
0.767 0.039 0.061 0.261 0.039 0.004
CABG, coronary artery bypass grafting; CKD, chronic kidney disease; IHD, ischemic heart disease; LDL-C, low-density lipoprotein cholesterol; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
achievement (Table 6). Patients with health insurance coverage provided by the civil servant medical benefit scheme (CSMBS) and social security scheme (SSS) were more likely to achieve LDL-C goal than those with the universal coverage scheme (UCS).
The present study aimed to determine temporal trends of highintensity statin therapy and LDL-C goal achievement among ACS patients. Our finding indicates that a higher proportion of ACS patients were prescribed high-intensity statins after the release of the 2013 ACC/AHA guideline on blood cholesterol management [3], rising from 10% in 2013 to 88% by 2016; however, the proportion of ACS patients achieving LDL-C goal remained suboptimal over the study period. Because the benefits of statin therapy in ASCVD reduction correlate strongly with the extent of LDL-C reduction [1,18], our findings imply that in a real-world setting, the ACS patients who are prescribed intensive statin therapy may not derive the maximal benefits in ASCVD risk reduction as intended by the guidelines due to suboptimal LDL-C reduction. This should promote more discussion among health policy makers on statin treatment to improve the quality of care for ACS patients. The ACS patients are stratified as being at very high risk of cardiovascular events; thus, the ACC/AHA guideline [3] has emphasized providing high-intensity statins to achieve at least 50% LDL-C reduction, whereas the ESC/EAS guideline [4] has recommended a target-driven therapy to achieve LDL-C <70 mg/ dL or at least 50% LDL-C reduction. Therefore, both guidelines agree upon achieving at least 50% reduction of LDL-C with high-intensity statins for most ACS patients. Our data reveal that high-intensity statins were prescribed to a higher proportion of ACS patients over time; however, by average the 50% LDL-C reduction goal was achieved in only 23% of the patients over the 5-year period. These findings support a recommendation for a follow-up LDL-C measurement in ACS patients after the initiation of statin therapy,
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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Table 4 Trends in the proportion of patients achieving LDL-C goal within 120 days after discharge between 2013 and 2017. Criteria defining LDL-C goal achievement
50% LDL-C reduction LDL-C < 70 mg/dL Either of the above criteria
Year of hospitalization Overall (N=427) n (%)
2013 (N = 97) n (%)
2014 (N = 83) n (%)
2015 (N = 91) n (%)
2016 (N = 73) n (%)
2017 (N = 83) n (%)
99 (23.2) 150 (35.1) 185 (43.3)
15 (15.5) 26 (26.8) 31 (32.0)
17 (20.5) 29 (34.9) 34 (41.0)
31 (34.1) 40 (44.0) 50 (55.0)
21 (28.8) 29 (39.7) 37 (50.7)
15 (18.1) 26 (31.3) 33 (39.8)
p-value for trend
0.561 0.584 0.402
LDL-C, low-density lipoprotein cholesterol.
Table 5 Characteristics of acute coronary syndrome patients according to LDL-C goal achievement at 120 days after discharge. Characteristics
All patients (N = 427) n (%)
LDL-C goal achieved (N = 185) n (%)
LDL-C goal not achieved (N = 242) n (%)
p-value
Age 75 years Female Current smoker Family history of CHD Health insurance UCS CSMBS SSS Comorbidities Diabetes mellitus Hypertension CKD stage III–V Index events Unstable angina STEMI NSTEMI Revascularization PCI CABG Lipid profiles LDL-C < 70 mg/dL LDL-C 70–100 mg/dL LDL-C > 100 mg/dL LDL-C (mean SD) (mg/dL) Number of home medications Cardiovascular medications Aspirin P2Y12 inhibitors Beta-blockers ACEI or ARB High-intensity statins
307 (71.9) 155 (36.3) 110 (25.8) 6 (1.4)
135 (73.0) 66 (35.7) 43 (23.2) 4 (2.2)
172 (71.1) 89 (36.8) 67 (27.7) 2 (0.8)
0.665 0.815 0.298 0.227 0.052
305 (71.4) 93 (21.8) 29 (6.8)
121 (65.4) 48 (26.0) 16 (8.6)
184 (76.0) 45 (18.6) 13 (5.4)
127 (29.7) 185 (43.3) 29 (6.8)
55 (29.7) 74 (40.0) 11 (5.9)
72 (29.8) 111 (45.9) 18 (7.4)
37 (8.7) 160 (37.5) 230 (53.8)
15 (8.1) 78 (42.2) 92 (49.7)
22 (9.1) 82 (33.9) 138 (57.0)
264 (61.8) 23 (5.4)
115 (62.2) 11 (6.0)
149 (61.6) 12 (5.0)
49 (11.5) 84 (19.7) 294 (68.8) 121.9 44.6 8.6 2.2
33 (17.8) 37 (20.0) 115 (62.2) 120.2 51.3 8.7 2.2
16 (6.6) 47 (19.4) 179 (74.0) 123.2 38.7 8.5 2.2
0.507 0.390
408 399 333 306 255
172 (93.0) 172 (93.0) 139 (75.1) 133 (71.9) 126 (68.1)
236 (97.5) 227 (93.8) 194 (80.2) 173 (71.5) 129 (53.3)
0.032 0.732 0.214 0.927 0.002
(95.6) (93.4) (78.0) (71.7) (59.7)
0.996 0.225 0.544 0.215
0.901 0.654 0.001
ACEI, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CHD, coronary heart disease; CKD, chronic kidney disease; CSMBS, civil servant medical benefit scheme; LDL-C, low-density lipoprotein cholesterol; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; SSS, social security scheme; STEMI, ST-elevation myocardial infarction; UCS, universal coverage scheme.
Table 6 Independent predictors of LDL-C goal achievement at 120 days after discharge. Variables Health insurance UCS CSMBS SSS Lipid profiles LDL-C < 70 mg/dL LDL-C 70–100 mg/dL LDL-C > 100 mg/dL Aspirin High-intensity statins
Adjusted ORs
95%CI
p-value
Reference 1.65 2.39
1.01–2.68 1.08–5.27
0.045 0.031
Reference 0.35 0.26 0.32 2.13
0.16–0.75 0.13–0.51 0.11–0.90 1.40–3.24
0.007 <0.001 0.031 <0.001
CSMBS, civil servant medical benefit scheme; LDL-C, low-density lipoprotein cholesterol; SSS, social security scheme; UCS, universal coverage scheme.
even the high-intensity one, to confirm an optimal response to lipid-lowering therapy. In support of this, Wang and colleagues reported that a lipid measurement in ACS patients was associated
with a higher likelihood to achieve LDL-C goals [19]. In case a maximally tolerated dose of statins has been given with good patient adherence, but the LDL-C goal is still not achieved, then a non-statin therapy, for example ezetimibe or PCSK9 inhibitors, may be considered to maximize the ASCVD risk reduction [4]. After the release of the 2013 ACC/AHA guideline [3], we observed an increasing trend in the proportion of ACS patients who were prescribed high-intensity statin therapy. Our finding agrees well with the results of a previous study. Rosenson and colleagues [13] also found a significant increase in the proportion of MI patients who were prescribed high-intensity statins in 2014; however, the results were not available after 2014. The results of our study extend further and show that the percentage of highintensity statin utilization for ACS patients increased greatly in 2015 and remained high, approaching nearly 90% in 2017. In contrast, studies enrolling a patient cohort prior to 2013 reported a much lower rate of high-intensity statin utilization [8,12,15,19]. A few reasons could explain this observation including the release of
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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the 2013 ACC/AHA guideline emphasizing uses of high-intensity statins for patients with ASCVD, and the availability of generic atorvastatin formulations at a lower cost [13]. A rising trend of high-intensity statin therapy after 2013 also indicates a high adherence to the evidence-based standards of care for ACS patients among the physicians. We observed that patients with a higher baseline LDL-C (>100 mg/dL) on admission were more likely to receive high-intensity statins before discharge, independently of other factors. Our finding is consistent with previous studies [8,20], suggesting that the baseline LDL-C is probably one of the significant factors in deciding whether to prescribe high-intensity statins for ACS patients. However, the ACC/AHA and ESC/EAS guidelines consider ACS patients as very high risk for recurrent cardiovascular events, and ACS patients should receive high-intensity statins regardless of LDL-C levels, unless with statin intolerance or aged over 75 years. Hence, we believe this important message should be further emphasized to health care providers to promote the optimal use of high-intensity statins in ACS patients. Another factor independently associated with high-intensity statin use in this study included age <75 years. Other studies also found older age as an important factor associated with the reduction of high-intensity statin therapy in patients with ASCVD [19,20]. The 2016 ESC/EAS guideline recommends high-intensity statin treatment for older patients with ASCVD in the same manner as younger patients with a class I recommendation. The 2013 ACC/ AHA guideline has taken a different approach and recommended a moderate-intensity statin for patients older than 75 years with ASCVD. The issue of how to optimize statin therapy in the older patients with ASCVD has been much debated. The results of MIRACL study demonstrated no difference in cardiovascular and safety outcomes among ACS patients 65 vs. <65 years of age receiving high-intensity statins [21]. A recent meta-analysis reported that in the secondary prevention population, statins reduced major cardiovascular events irrespective of age, including those older than 75 years [22]. In contrast, a recent study using real-world data in elderly statin users after ACS, the number of recurrent MIs and deaths that could be prevented by aggressive statin treatment was projected as negligible [23,24]. Additionally, age 65 years has been reported as the most important risk factor for rhabdomyolysis among statin users [25,26]. Collectively, we believe that clinicians should be more judicious in providing intensive statin therapy to older patients, given the higher prevalence of multi-comorbidities, potential adverse drug effects, drug interactions due to polypharmacy, and limited life expectancy in the older population [23,24]. A significant association was also observed between highintensity statin therapy and the prescription of P2Y12 inhibitors and beta-blockers among ACS patients (Table 4). It was plausible that physicians who prescribed high-intensity were more likely those physicians who complied with guideline-directed medical therapies and thus prescribed P2Y12 inhibitors and beta-blockers for ACS patients [27]. In support of this explanation, a previous study reported that statin treatment was associated with other standard-of-care therapies in a large managed-care population with ischemic heart disease and diabetes in the USA [28]. Over the 5-year period, we observed 43.3% of ACS patients achieved LDL-C goal within 120 days after discharge. Achieving an LDL-C goal of less than 70 mg/dL was associated with a lower risk of cardiovascular events in a real-life cohort of Thai ACS patients [29]. The suboptimal LDL-C goal achievement in ACS patients has been reported in previous studies [9,12,15,30,31]. The MAINTAIN registry reported 31% of ACS patients receiving high-intensity statin therapy attained LDL-C target at 1 year after hospital discharge [9]. In the DYSIS II study, 18.9% of ACS patients attained the LDL-C goal <70 mg/dL [30]. A previous study in Thailand
reported 25% of ACS patients receiving high-intensity achieved LDL-C goal [12]. The proportion of LDL-C goal achievement defined by either criteria in our study appears a little higher than those reported in the aforementioned studies. The disparity observed in our and other studies could be explained by a difference in the goal achievement definition, and a higher proportion of our ACS patients receiving high-intensity statins, contributing to the higher LDL-C goal achievement in our study. We observed that the proportion of patients achieving LDL-C goal increased during 2014 and 2015, but noticeably declined thereafter. The downward trend in the achievement of LDL-C after 2015 could not be explained by the difference in baseline LDL-C levels because we did not observe any significant difference in the baseline LDL-C over the 5-year period (data not shown). Additionally, the proportion of patients who received highintensity statins remained high; thus, it was unlikely that the reduction in high-intensity statin prescriptions could explain the lower percentage of LDL-C goal achievement after 2015. Atorvastatin 40 mg was the most commonly prescribed high-intensity statin in our study, and the drug became available in several formulations in recent years. Thus, the switch between atorvastatin formulations could be one of the explanations for this observation. Another possible reason included a lower adherence of statin among statin users related to the fear of statin-associated adverse effects, particularly following the distribution of findings from large observational studies. Examples included reports of statin-associated muscle symptoms, newly-diagnosed diabetes mellitus, hemorrhagic stroke, and cataracts [26]. Other plausible reasons could involve a change in the method of LDL-C measurement at the study hospital, and even a random error due to a rather small sample size in our study. Whatever the reason is, this observation further highlights the importance of obtaining lipid measurement to monitor therapeutic response and adherence after statin initiation. The issue of the downward trend in LDL-C goal achievement, despite high-intensity statin therapy, deserves further investigation. In multivariable analysis, receiving high-intensity statins increased the likelihood of achieving LDL-C goal by two-fold (OR 2.13, 95%CI 1.40–3.24, p < 0.001). A previous study conducted in post-MI patients also reported the same finding [11]. However, one study came to a different conclusion and found no association between statin intensity and LDL-C goal achievement [12]. This discrepancy on the influence of statin intensity on LDL-C goal achievement could be attributed to a disparity in the definition of LDL-C goal achievement, the study population, the time point in determining goal achievement. Some other unmeasured variables could also confound the association. Nevertheless, a strong association between high-intensity statins and LDL-C goal achievement observed in our study suggests that this is more likely not to occur by chance. The baseline LDL-C was also identified as a predictor of LDL-C goal achievement in the present study. Other studies also reported the same finding [10,32,33]. In our study, ACS patients with a higher baseline LDL-C (70 mg/dL vs. <70 mg/dL) were less likely to achieve the LDL-C goal defined by either of the criteria. Thus, a higher baseline LDL-C helps to define a target group for statin therapy optimization. Care optimization should incorporate not only prescriptions of high-intensity statins which have been shown predictive of LDL-C goal achievement, but also a follow-up lipid measurement to confirm patient response, and patient motivation on adherence to statin therapy. This study has some limitations. First, this was an observational study with inherent limitations in making causal association between the measured variables. However, the findings in our study agree with previous studies, and thus this could partly argue for the validity of our conclusions. Second, the use of statins was
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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based on prescription data in the medical database; therefore, we could not ascertain whether patients have taken statins as prescribed, this plausibly being one of the reasons for not achieving LDL-C goal. A recent study reported a low adherence to high-intensity statin therapy among patients discharged with MI [34], and thus it is conceivable that the low adherence rate could contribute to the suboptimal LDL-C goal achievement in our study. Finally, we recruited ACS patients from a single tertiary-care, teaching hospital; therefore, generalization of the findings to other settings requires further confirmation. Conclusions In a more recent cohort of Thai ACS patients, a higher proportion of patients received high-intensity statin therapy before discharge. However, the proportion of patients who achieved LDL-C goal did not increase accordingly. Several factors are identified as predictors of high-intensity statin therapy and LDL-C goal achievement. These predictors may be useful in planning to optimize statin therapy for ACS patients. Our findings should promote more discussion among health policy makers to improve statin treatment and quality of care for ACS patients. Funding This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors. Disclosures The authors declare that there is no conflict of interest. References [1] Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670–81. [2] Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012;380:581–90. [3] Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889–934. [4] Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2016;37:2999–3058. [5] Navarese EP, Kowalewski M, Andreotti F, Van Wely M, Camaro C, Kolodziejczak M, et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol 2014;113:1753–64. [6] Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001;285:1711–8. [7] Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495–504. [8] Javed U, Deedwania PC, Bhatt DL, Cannon CP, Dai D, Hernandez AF, et al. Use of intensive lipid-lowering therapy in patients hospitalized with acute coronary syndrome: an analysis of 65,396 hospitalizations from 344 hospitals participating in get with the Guidelines (GWTG). Am Heart J 2010;160:1130–6. [9] Melloni C, Shah BR, Ou FS, Roe MT, Smith Jr SC, Pollack Jr CV, et al. Lipidlowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: results from the medications applied and sustained over time (MAINTAIN) registry. Am Heart J 2010;160:1121–9. e1. [10] Praipaisarnkit K, Wongpraparut N, Pongakasira R. Low-density lipoprotein cholesterol goal attainment among post myocardial infarction patients on lipid lowering therapy at Siriraj Outpatient Clinic. J Med Assoc Thai 2014;97:S147–54.
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[24] Kosuma P, Jedsadayanmata A. Prevalence and predictors of statin treatment among patients with chronic heart failure at a tertiary-care center in Thailand. Clin Med Insights Cardiol 2019;13:1–8. [25] Schech S, Graham D, Staffa J, Andrade SE, La Grenade L, Burgess M, et al. Risk factors for statin-associated rhabdomyolysis. Pharmacoepidemiol Drug Saf 2007;16:352–8. [26] Newman CB, Preiss D, Tobert JA, Jacobson TA, Page IIRL, Goldstein LB, et al. Statin safety and associated adverse events. A scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2019;39:e38–81. [27] Jneid H, Addison D, Bhatt DL, Fonarow GC, Gokak S, Grady KL, et al. AHA/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association task force on performance measures. J Am Coll Cardiol 2017;70:2048–90. [28] Steen DL, Khan I, Becker L, Foody JM, Gorcyca K, Sanchez RJ, et al. Patterns and predictors of lipid-lowering therapy in patients with atherosclerotic cardiovascular disease and/or diabetes mellitus in 2014: insights from a large US managed-care population. Clin Cardiol 2017;40:155–62. [29] Chinwong D, Patumanond J, Chinwong S, Siriwattana K, Gunaparn S, Hall JJ, et al. Low-density lipoprotein cholesterol of less than 70 mg/dL is associated with fewer cardiovascular events in acute coronary syndrome patients: a reallife cohort in Thailand. Ther Clin Risk Manag 2015;11:659–67. [30] Gitt AK, Lautsch D, Ferriѐres J, De Ferrari GM, Vyas A, Baxter CA, et al. Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: results from the Dyslipidemia International Study II. Atherosclerosis 2017;266:158–66. [31] Andrikopoulos G, Tzeis S, Nikas N, Richter D, Pipilis A, Gotsis A, et al. 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Original article
Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome Yuttana Wongsalap (PharmD)a, Arom Jedsadayanmata (PharmD PhD)b,c,d,* a
School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand c Drug Information and Consumer Protection Center, Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand d Center of Excellence in Pharmacy Practice and Management Research, Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 June 2019 Received in revised form 5 August 2019 Accepted 13 August 2019 Available online xxx
Background: Previous studies on the use of high-intensity statins and low-density lipoprotein cholesterol (LDL-C) goal achievement were mostly conducted in patients with acute coronary syndrome (ACS) receiving care before 2013. We aimed to determine trends and predictors of high-intensity statin therapy and LDL-C goal achievement in a more recent cohort of Thai ACS patients. Methods: We analyzed data from electronic databases of ACS patients at a tertiary-care, teaching hospital in Thailand between 2013 and 2017. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement after hospital discharge were determined with logistic regression analysis. Results: Among 1753 ACS patients, 987 (56.3%) received high-intensity statin at discharge. A higher proportion of ACS patients were prescribed high-intensity statins over time (p = 0.033 for linear trend), rising from 10% in 2013 to 88% in 2017. Independent predictors of high-intensity statin therapy included age 75 years, a diagnosis of myocardial infarction, receiving P2Y12 inhibitors, and beta-blockers. Within 120 days after discharge, 427 (24.4%) patients had follow-up LDL-C measurements. Overall, 185 (43.3%) patients achieved LDL-C goals based on either of the following criteria: LDL-C <70 mg/dL or 50% reduction in the baseline LDL-C. There was a non-significant trend (p = 0.402 for linear trend) in the proportion of patients achieving LDL-C goals over the study period. Independent predictors of achieving LDL-C goal included high-intensity statin therapy after discharge and lower baseline LDL-C on admission. Conclusions: In a more recent cohort of Thai ACS patients, a higher proportion of patients were prescribed high-intensity statins before discharge over the study period. However, the proportion of patients who achieved LDL-C goal did not increase accordingly. This finding should promote more discussion among health policy makers to improve statin treatment and quality of care for ACS patients. © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Acute coronary syndrome Goal achievement Intensity Low-density lipoprotein cholesterol Statin Predictor Trend
Introduction The elevated level of low-density lipoprotein cholesterol (LDLC) has been recognized as an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Lowering LDL-C with statins reduces adverse cardiovascular events in patients with or without established ASCVD [1,2]. The American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol emphasizes initiating statin therapy at the appropriate intensity based on patient’s ASCVD risk [3].
* Corresponding author at: Faculty of Pharmacy, Thammasat University, Khong Luang, Pathum Thani 12120, Thailand. E-mail address: [email protected] (A. Jedsadayanmata).
While the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guideline underscores the achievement of LDL-C target based on ASCVD risk [4]. Patients with acute coronary syndrome (ACS) are at heightened risk of cardiovascular events [3,4]. Studies have shown that statin therapy significantly reduces these cardiovascular events among ACS patients, particularly when started early after the events [5–7]. Further, a more intensive statin therapy has proved to be more efficacious than the lower intensity [5–7]. Despite the evidence of the potential benefits of high-intensity statins, previous studies using real-world data indicated that the intensity of statin therapy was suboptimal and the LDL-C goal achievement remained low among ACS patients [8–14]. Of note, however, most of these studies were conducted with a patient cohort receiving care before 2013, and thus the results may not reflect clinical practice on blood
https://doi.org/10.1016/j.jjcc.2019.08.012 0914-5087/© 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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cholesterol management after the release of more recent guidelines by ACC/AHA and ESC/EAS [3,4]. In the present study, by recruiting a more recent cohort of Thai ACS patients between 2013 and 2017, we aimed to determine temporal trends and predictors of high-intensity statin therapy and the LDL-C goal achievement among ACS patients discharged with statins. The results will provide more updated information to improve quality of care for ACS patients.
based on the following criteria: (1) an achievement of 50% reduction in LDL-C level from baseline, (2) an attainment of LDL-C level <70 mg/dL, and (3) either of the criteria in (1) or (2). The 120day after discharge was chosen as the time point to determine goal achievement based on the study showing that most ACS patients achieved goal within 120 days after discharge if they were going to achieve LDL-C goals [15]. Statistical analysis
Methods Study population and setting We retrospectively reviewed data of the ACS patients who were admitted to a 1000-bed, tertiary-care, teaching hospital in Phitsanulok province located in northern Thailand. The hospital served as a referral-center for advanced and interventional cardiovascular care in the lower northern region of Thailand. Patient data were retrieved from electronic medical and administrative claims database at the study hospital. Patients were eligible for recruitment if they were 18 years of age or older and hospitalized with ACS between January 1, 2013, and November 30, 2017. ACS was defined as a ST-segment elevation myocardial infarction (STEMI), a non-ST-segment elevation myocardial infarction (NSTEMI), or unstable angina (UA). Eligible ACS patients were identified with the ICD-10 (International Statistical Classification of Diseases and Related Health Problems, 10th Revision) diagnosis codes of I20.0 (UA) and I21.x (acute MI). Other eligible criteria included having a lipid profile drawn within 24 h after hospitalization, no record of statin therapy at least 6 months prior to admission, and were prescribed statin therapy before hospital discharge. Patients were excluded if they did not survive until hospital discharge or were transferred to other hospitals for further management. The study protocol received an ethical approval by the Institutional Review Board on Human Research at the study hospital prior to data collection. The informed consent from patients was not required. Data collection The electronic medical and claims database were all linked by the patient unique identification number. The claims database provided information on patient demographics, health insurance status, principal diagnoses at index hospitalization, comorbidities, interventions, and medications received during hospitalization and at outpatient visits. Comorbidities were identified with the ICD-10. Interventions, e.g. a revascularization procedure, were identified using ICD-9 CM (The International Classification of Diseases, 9th Revision, Clinical Modification). The medical database was reviewed to retrieve information on smoking status, the family history of coronary heart disease (CHD), and the confirmation of no statin use prior to admission. Statin therapy at hospital discharge was identified through the electronic claims database. Statins available at the study hospital included atorvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. Statin intensity was defined in accordance with the 2013 ACC/AHA blood cholesterol guideline [3]. High-intensity statin therapy consisted of atorvastatin prescribed at 40 or 80 mg daily, rosuvastatin at 20 or 40 mg daily, and simvastatin at 80 mg daily. The rest of statin therapy not aforementioned were considered as a low-to-moderate intensity. The lipid profiles were available from electronic reports of the central laboratory department and were linked to other patient data by the patient unique identification number. We defined the LDL-C goal achievement within 120 days after hospital discharge
Baseline characteristics were summarized and presented as frequency and proportions (percentage) for categorical variables. Numeric variables were summarized as means and standard deviations (SDs). To determine the proportion of patients receiving highintensity statins or achieving LDL-C goal, we stratified patients by years of recruitment into the study and calculated the proportion of patients receiving high-intensity statins or achieving LDL-C goal by dividing the total number of patients receiving highintensity statins or achieving LDL-C goal (nominators) with the total number of ACS patients (denominators) within that year. A time trend analysis was performed by unadjusted logistic regression as described previously [16,17]. The model was constructed with the proportion of patients who received highintensity statins or achieved LDL-C goal stratified by years of recruitment as dependent variables and time (years) from 1 to 5 as independent variables as follows: LnðEðn=NÞÞ ¼ constant þ b Year where n denotes an estimated number of patients receiving highintensity statins or achieving LDL-C goal in each year, and N denotes the total number of patients in the same year, and Year denotes a categorical variable from 1 to 5 for the respective years between 2013 and 2017. To identify predictors of receiving high-intensity statins or achieving LDL-C goal, we categorized patients into 2 groups either by the statin intensity (high vs. low/moderate) or the achievement of LDL-C goal (achieved vs. not achieved). The baseline characteristics between groups were compared, using chi-square or Fisher’s exact test as appropriate for categorical variables, and independent t-test for numeric variables. Potential predictors were identified as baseline variables with a p-value of <0.2 in the univariable analysis, and were all entered into multivariable logistic regression to identify independent predictors of high-intensity statin therapy or achieving LDL-C goal accordingly. All statistical analyses were performed two-sided, with a pvalue of <0.05 considered as statistically significant. All statistical analyses were performed using Stata software (StataCorp LLC, College Station, TX, USA). Results Intensity of statin therapy A total of 4447 patients hospitalized with ACS between 2013 and 2017 were identified. Among them, 2739 (96%) were prescribed statins at hospital discharge. Patients who had documented use of statins prior to admission or had no LDL-C level drawn within 24 h after admission were excluded. The remaining 1753 patients were recruited into this study (Fig. 1). Overall, 987 (56.3%) patients were prescribed high-intensity statins over a 5-year period (Table 1). The remaining 766 (43.7%) patients received statins at the low-to-moderate intensity prior to discharge. The prescribed statins included atorvastatin 80 mg daily (n = 5), atorvastatin 40 mg daily (n = 980), and rosuvastatin 20 mg daily (n = 2). Less than 1% of patients were prescribed non-statin
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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Fig. 1. Patient flow chart. ACS, acute coronary syndrome; LDL-C, low-density lipoprotein cholesterol.
therapy. When categorizing patients by years of hospitalization, we observed a noticeably rise in the proportions of ACS patients who were prescribed high-intensity statins after 2013. In 2013, 10% of the cohort were prescribed high-intensity statins, but the proportions increased to 32% and 88% in 2014 and 2016, respectively. A significant linear trend (p = 0.033 for trend) in the increased proportion of patients receiving high-intensity statins over the 5-year period was observed (Table 1). Table 2 shows baseline characteristics of the entire ACS patients in this study. The mean age was 67.9 12.4 years, and 63% of them were male. Ninety percent of the cohort were diagnosed with NSTEMI (47.8%) or STEMI (43.1%), and 62.9% had undergone PCI during the index hospitalization. Table 2 also compares characteristics of the patients who were prescribed high-versus low-tomoderate-intensity statins. Patients with the following characteristics were more likely to receive high-intensity statins before discharge: being 75 years of age, male gender, current smokers, a higher baseline LDL-C on admission, having undergone percuta-
Table 1 Trend in the proportion of patients who were prescribed high-intensity statins before discharge between 2013 and 2017. Years
Total patients
n (%)
p-value for trend
2013 2014 2015 2016 2017 Total
340 405 408 319 281 1753
34 (10.0) 130 (32.1) 293 (71.8) 281 (88.1) 249 (88.6) 987 (56.3)
.033
neous coronary intervention (PCI), receiving P2Y12 inhibitors or
b-blockers before discharge.
Multivariable logistic regression identified independent predictors of high-intensity statin treatment (Table 3). Age 75 years, having diagnosis of MI in comparison to unstable angina, the LDL-C level > 100 mg/dL on admission, having undergone PCI, receiving P2Y12 inhibitors or beta-blockers at discharge all increased the likelihood of receiving high-intensity statin therapy independently of other factors. LDL-C goal achievement We define LDL-C goal achievement by the criteria described under the Methods section. Table 4 shows the proportion of ACS patients who achieved LDL-C goal within 120 days after discharge according to the years of patient recruitment over a 5-year period. Overall, 23.2% of patients achieved 50% reduction in LDL-C, but a higher proportion (35.1%) achieved the LDL-C level <70 mg/dL. Based on either of the criteria, 185 (43.4%) were considered to achieve the LDL-C goal. We observed the highest proportion (55%) of patients achieving LDL-C goal in the year 2015, but the proportions declined in 2016 and 2017. There was a non-significant linear trend (p = 0.402) in the proportion of patients achieving LDL-C goal over the 5-year period. Table 5 compares characteristics of ACS patients who achieved versus did not achieve LDL-C goal at 120 days after discharge. Patients who had a lower baseline LDL-C on admission and received high-intensity statins before discharge were more likely to achieve LDL-C goals within 120 days. Multivariable analysis identified a higher baseline LDL-C as the negative predictor, whereas high-intensity statins as a positive predictor of LDL-C goal
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Table 2 Characteristics of acute coronary syndrome patients according to statin intensity at discharge. Characteristics
All patients (N = 1753) n (%)
High intensity (N = 987 n (%)
Low/moderate intensity (N = 766) n (%)
p-value
Age 75 years Female Current smoker Family history of CHD Health insurance UCS CSMBS SSS Comorbidities Diabetes mellitus Hypertension History of CHD Ischemic stroke CKD stage III–V Index events Unstable angina STEMI NSTEMI Revascularization PCI CABG Lipid profiles LDL-C < 70 mg/dL LDL-C 70-100 mg/dL LDL-C > 100 mg/dL LDL-C (mean SD) (mg/dL) Number of home medications Cardiovascular medications Aspirin P2Y12 inhibitors Beta-blockers ACEI or ARB
1,238 (70.6) 644 (36.7) 470 (26.8) 25 (1.4)
781 (79.1) 319 (32.3) 298 (30.2) 17 (1.7)
457 (59.7) 325 (42.4) 172 (22.5) 8 (1.0)
<0.001 <0.001 <0.001 0.235 0.335
1304 (74.4) 353 (20.1) 96 (5.5)
721 (73.0) 208 (21.1) 58 (5.9)
583 (76.1) 145 (18.9) 38 (5.0)
452 (25.8) 682 (38.9) 10 (0.6) 15 (0.9) 103 (5.9)
263 (26.7) 358 (36.3) 3 (0.3) 9 (0.9) 46 (4.7)
189 (24.7) 324 (42.3) 7 (0.9) 6 (0.8) 57 (7.4)
160 (9.1) 756 (43.1) 837 (47.8)
55 (5.6) 478 (48.4) 454 (46.0)
105 (13.7) 278 (36.3) 383 (50.0)
1103 (62.9) 33 (1.9)
701 (71.0) 23 (2.3)
402 (52.5) 10 (1.3)
211 (12.0) 454 (25.9) 1088 (62.1) 117.1 44.9 8.4 2.2
101 (10.2) 231 (23.4) 655 (66.4) 122.0 47.4 8.5 2.2
110 (14.4) 223 (29.1) 433 (56.5) 110.9 40.6 8.3 2.3
<0.001 0.178
1672 (95.4) 1618 (92.3) 1279 (73.0) 1220 (69.6)
951 (96.4) 940 (95.2) 759 (76.9) 692 (70.1)
721 (94.1) 678 (88.5) 520 (67.9) 528 (68.9)
0.028 <0.001 <0.001 0.593
0.349 0.010 0.115 0.772 0.014 <0.001
<0.001 0.117 <0.001
ACEI, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CHD, coronary heart disease; CKD, chronic kidney disease; CSMBS, civil servant medical benefit scheme; LDL-C, low-density lipoprotein cholesterol; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; SSS, social security scheme; STEMI, ST-elevation myocardial infarction; UCS, universal coverage scheme.
Discussion
Table 3 Independent predictors of high-intensity statin therapy at discharge. Variables
Adjusted ORs
95%CI
p-value
Age 75 years Female Current smoker Hypertension Chronic IHD CKD Index event Unstable angina STEMI NSTEMI PCI CABG Lipid profiles LDL-C < 70 mg/dL LDL-C 70–100 mg/dL LDL-C > 100 mg/dL Number of home medications Aspirin P2Y12 inhibitors Beta-blockers
2.38 0.89 1.07 0.86 0.70 0.83
1.90–2.99 0.71–1.12 0.83–1.37 0.69–1.07 0.16–3.13 0.54–1.29
<0.001 0.313 0.612 0.166 0.644 0.414
Reference 2.05 2.02 1.68 1.92
1.36–3.11 1.38–2.95 1.31–2.16 0.87–4.23
0.001 <0.001 <0.001 0.104
Reference 1.05 1.39 1.05 0.73 1.63 1.41
0.75–1.49 1.02–1.91 0.99–1.10 0.42–1.26 1.03–2.58 1.11–1.79
0.767 0.039 0.061 0.261 0.039 0.004
CABG, coronary artery bypass grafting; CKD, chronic kidney disease; IHD, ischemic heart disease; LDL-C, low-density lipoprotein cholesterol; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
achievement (Table 6). Patients with health insurance coverage provided by the civil servant medical benefit scheme (CSMBS) and social security scheme (SSS) were more likely to achieve LDL-C goal than those with the universal coverage scheme (UCS).
The present study aimed to determine temporal trends of highintensity statin therapy and LDL-C goal achievement among ACS patients. Our finding indicates that a higher proportion of ACS patients were prescribed high-intensity statins after the release of the 2013 ACC/AHA guideline on blood cholesterol management [3], rising from 10% in 2013 to 88% by 2016; however, the proportion of ACS patients achieving LDL-C goal remained suboptimal over the study period. Because the benefits of statin therapy in ASCVD reduction correlate strongly with the extent of LDL-C reduction [1,18], our findings imply that in a real-world setting, the ACS patients who are prescribed intensive statin therapy may not derive the maximal benefits in ASCVD risk reduction as intended by the guidelines due to suboptimal LDL-C reduction. This should promote more discussion among health policy makers on statin treatment to improve the quality of care for ACS patients. The ACS patients are stratified as being at very high risk of cardiovascular events; thus, the ACC/AHA guideline [3] has emphasized providing high-intensity statins to achieve at least 50% LDL-C reduction, whereas the ESC/EAS guideline [4] has recommended a target-driven therapy to achieve LDL-C <70 mg/ dL or at least 50% LDL-C reduction. Therefore, both guidelines agree upon achieving at least 50% reduction of LDL-C with high-intensity statins for most ACS patients. Our data reveal that high-intensity statins were prescribed to a higher proportion of ACS patients over time; however, by average the 50% LDL-C reduction goal was achieved in only 23% of the patients over the 5-year period. These findings support a recommendation for a follow-up LDL-C measurement in ACS patients after the initiation of statin therapy,
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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Table 4 Trends in the proportion of patients achieving LDL-C goal within 120 days after discharge between 2013 and 2017. Criteria defining LDL-C goal achievement
50% LDL-C reduction LDL-C < 70 mg/dL Either of the above criteria
Year of hospitalization Overall (N=427) n (%)
2013 (N = 97) n (%)
2014 (N = 83) n (%)
2015 (N = 91) n (%)
2016 (N = 73) n (%)
2017 (N = 83) n (%)
99 (23.2) 150 (35.1) 185 (43.3)
15 (15.5) 26 (26.8) 31 (32.0)
17 (20.5) 29 (34.9) 34 (41.0)
31 (34.1) 40 (44.0) 50 (55.0)
21 (28.8) 29 (39.7) 37 (50.7)
15 (18.1) 26 (31.3) 33 (39.8)
p-value for trend
0.561 0.584 0.402
LDL-C, low-density lipoprotein cholesterol.
Table 5 Characteristics of acute coronary syndrome patients according to LDL-C goal achievement at 120 days after discharge. Characteristics
All patients (N = 427) n (%)
LDL-C goal achieved (N = 185) n (%)
LDL-C goal not achieved (N = 242) n (%)
p-value
Age 75 years Female Current smoker Family history of CHD Health insurance UCS CSMBS SSS Comorbidities Diabetes mellitus Hypertension CKD stage III–V Index events Unstable angina STEMI NSTEMI Revascularization PCI CABG Lipid profiles LDL-C < 70 mg/dL LDL-C 70–100 mg/dL LDL-C > 100 mg/dL LDL-C (mean SD) (mg/dL) Number of home medications Cardiovascular medications Aspirin P2Y12 inhibitors Beta-blockers ACEI or ARB High-intensity statins
307 (71.9) 155 (36.3) 110 (25.8) 6 (1.4)
135 (73.0) 66 (35.7) 43 (23.2) 4 (2.2)
172 (71.1) 89 (36.8) 67 (27.7) 2 (0.8)
0.665 0.815 0.298 0.227 0.052
305 (71.4) 93 (21.8) 29 (6.8)
121 (65.4) 48 (26.0) 16 (8.6)
184 (76.0) 45 (18.6) 13 (5.4)
127 (29.7) 185 (43.3) 29 (6.8)
55 (29.7) 74 (40.0) 11 (5.9)
72 (29.8) 111 (45.9) 18 (7.4)
37 (8.7) 160 (37.5) 230 (53.8)
15 (8.1) 78 (42.2) 92 (49.7)
22 (9.1) 82 (33.9) 138 (57.0)
264 (61.8) 23 (5.4)
115 (62.2) 11 (6.0)
149 (61.6) 12 (5.0)
49 (11.5) 84 (19.7) 294 (68.8) 121.9 44.6 8.6 2.2
33 (17.8) 37 (20.0) 115 (62.2) 120.2 51.3 8.7 2.2
16 (6.6) 47 (19.4) 179 (74.0) 123.2 38.7 8.5 2.2
0.507 0.390
408 399 333 306 255
172 (93.0) 172 (93.0) 139 (75.1) 133 (71.9) 126 (68.1)
236 (97.5) 227 (93.8) 194 (80.2) 173 (71.5) 129 (53.3)
0.032 0.732 0.214 0.927 0.002
(95.6) (93.4) (78.0) (71.7) (59.7)
0.996 0.225 0.544 0.215
0.901 0.654 0.001
ACEI, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CHD, coronary heart disease; CKD, chronic kidney disease; CSMBS, civil servant medical benefit scheme; LDL-C, low-density lipoprotein cholesterol; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; SSS, social security scheme; STEMI, ST-elevation myocardial infarction; UCS, universal coverage scheme.
Table 6 Independent predictors of LDL-C goal achievement at 120 days after discharge. Variables Health insurance UCS CSMBS SSS Lipid profiles LDL-C < 70 mg/dL LDL-C 70–100 mg/dL LDL-C > 100 mg/dL Aspirin High-intensity statins
Adjusted ORs
95%CI
p-value
Reference 1.65 2.39
1.01–2.68 1.08–5.27
0.045 0.031
Reference 0.35 0.26 0.32 2.13
0.16–0.75 0.13–0.51 0.11–0.90 1.40–3.24
0.007 <0.001 0.031 <0.001
CSMBS, civil servant medical benefit scheme; LDL-C, low-density lipoprotein cholesterol; SSS, social security scheme; UCS, universal coverage scheme.
even the high-intensity one, to confirm an optimal response to lipid-lowering therapy. In support of this, Wang and colleagues reported that a lipid measurement in ACS patients was associated
with a higher likelihood to achieve LDL-C goals [19]. In case a maximally tolerated dose of statins has been given with good patient adherence, but the LDL-C goal is still not achieved, then a non-statin therapy, for example ezetimibe or PCSK9 inhibitors, may be considered to maximize the ASCVD risk reduction [4]. After the release of the 2013 ACC/AHA guideline [3], we observed an increasing trend in the proportion of ACS patients who were prescribed high-intensity statin therapy. Our finding agrees well with the results of a previous study. Rosenson and colleagues [13] also found a significant increase in the proportion of MI patients who were prescribed high-intensity statins in 2014; however, the results were not available after 2014. The results of our study extend further and show that the percentage of highintensity statin utilization for ACS patients increased greatly in 2015 and remained high, approaching nearly 90% in 2017. In contrast, studies enrolling a patient cohort prior to 2013 reported a much lower rate of high-intensity statin utilization [8,12,15,19]. A few reasons could explain this observation including the release of
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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the 2013 ACC/AHA guideline emphasizing uses of high-intensity statins for patients with ASCVD, and the availability of generic atorvastatin formulations at a lower cost [13]. A rising trend of high-intensity statin therapy after 2013 also indicates a high adherence to the evidence-based standards of care for ACS patients among the physicians. We observed that patients with a higher baseline LDL-C (>100 mg/dL) on admission were more likely to receive high-intensity statins before discharge, independently of other factors. Our finding is consistent with previous studies [8,20], suggesting that the baseline LDL-C is probably one of the significant factors in deciding whether to prescribe high-intensity statins for ACS patients. However, the ACC/AHA and ESC/EAS guidelines consider ACS patients as very high risk for recurrent cardiovascular events, and ACS patients should receive high-intensity statins regardless of LDL-C levels, unless with statin intolerance or aged over 75 years. Hence, we believe this important message should be further emphasized to health care providers to promote the optimal use of high-intensity statins in ACS patients. Another factor independently associated with high-intensity statin use in this study included age <75 years. Other studies also found older age as an important factor associated with the reduction of high-intensity statin therapy in patients with ASCVD [19,20]. The 2016 ESC/EAS guideline recommends high-intensity statin treatment for older patients with ASCVD in the same manner as younger patients with a class I recommendation. The 2013 ACC/ AHA guideline has taken a different approach and recommended a moderate-intensity statin for patients older than 75 years with ASCVD. The issue of how to optimize statin therapy in the older patients with ASCVD has been much debated. The results of MIRACL study demonstrated no difference in cardiovascular and safety outcomes among ACS patients 65 vs. <65 years of age receiving high-intensity statins [21]. A recent meta-analysis reported that in the secondary prevention population, statins reduced major cardiovascular events irrespective of age, including those older than 75 years [22]. In contrast, a recent study using real-world data in elderly statin users after ACS, the number of recurrent MIs and deaths that could be prevented by aggressive statin treatment was projected as negligible [23,24]. Additionally, age 65 years has been reported as the most important risk factor for rhabdomyolysis among statin users [25,26]. Collectively, we believe that clinicians should be more judicious in providing intensive statin therapy to older patients, given the higher prevalence of multi-comorbidities, potential adverse drug effects, drug interactions due to polypharmacy, and limited life expectancy in the older population [23,24]. A significant association was also observed between highintensity statin therapy and the prescription of P2Y12 inhibitors and beta-blockers among ACS patients (Table 4). It was plausible that physicians who prescribed high-intensity were more likely those physicians who complied with guideline-directed medical therapies and thus prescribed P2Y12 inhibitors and beta-blockers for ACS patients [27]. In support of this explanation, a previous study reported that statin treatment was associated with other standard-of-care therapies in a large managed-care population with ischemic heart disease and diabetes in the USA [28]. Over the 5-year period, we observed 43.3% of ACS patients achieved LDL-C goal within 120 days after discharge. Achieving an LDL-C goal of less than 70 mg/dL was associated with a lower risk of cardiovascular events in a real-life cohort of Thai ACS patients [29]. The suboptimal LDL-C goal achievement in ACS patients has been reported in previous studies [9,12,15,30,31]. The MAINTAIN registry reported 31% of ACS patients receiving high-intensity statin therapy attained LDL-C target at 1 year after hospital discharge [9]. In the DYSIS II study, 18.9% of ACS patients attained the LDL-C goal <70 mg/dL [30]. A previous study in Thailand
reported 25% of ACS patients receiving high-intensity achieved LDL-C goal [12]. The proportion of LDL-C goal achievement defined by either criteria in our study appears a little higher than those reported in the aforementioned studies. The disparity observed in our and other studies could be explained by a difference in the goal achievement definition, and a higher proportion of our ACS patients receiving high-intensity statins, contributing to the higher LDL-C goal achievement in our study. We observed that the proportion of patients achieving LDL-C goal increased during 2014 and 2015, but noticeably declined thereafter. The downward trend in the achievement of LDL-C after 2015 could not be explained by the difference in baseline LDL-C levels because we did not observe any significant difference in the baseline LDL-C over the 5-year period (data not shown). Additionally, the proportion of patients who received highintensity statins remained high; thus, it was unlikely that the reduction in high-intensity statin prescriptions could explain the lower percentage of LDL-C goal achievement after 2015. Atorvastatin 40 mg was the most commonly prescribed high-intensity statin in our study, and the drug became available in several formulations in recent years. Thus, the switch between atorvastatin formulations could be one of the explanations for this observation. Another possible reason included a lower adherence of statin among statin users related to the fear of statin-associated adverse effects, particularly following the distribution of findings from large observational studies. Examples included reports of statin-associated muscle symptoms, newly-diagnosed diabetes mellitus, hemorrhagic stroke, and cataracts [26]. Other plausible reasons could involve a change in the method of LDL-C measurement at the study hospital, and even a random error due to a rather small sample size in our study. Whatever the reason is, this observation further highlights the importance of obtaining lipid measurement to monitor therapeutic response and adherence after statin initiation. The issue of the downward trend in LDL-C goal achievement, despite high-intensity statin therapy, deserves further investigation. In multivariable analysis, receiving high-intensity statins increased the likelihood of achieving LDL-C goal by two-fold (OR 2.13, 95%CI 1.40–3.24, p < 0.001). A previous study conducted in post-MI patients also reported the same finding [11]. However, one study came to a different conclusion and found no association between statin intensity and LDL-C goal achievement [12]. This discrepancy on the influence of statin intensity on LDL-C goal achievement could be attributed to a disparity in the definition of LDL-C goal achievement, the study population, the time point in determining goal achievement. Some other unmeasured variables could also confound the association. Nevertheless, a strong association between high-intensity statins and LDL-C goal achievement observed in our study suggests that this is more likely not to occur by chance. The baseline LDL-C was also identified as a predictor of LDL-C goal achievement in the present study. Other studies also reported the same finding [10,32,33]. In our study, ACS patients with a higher baseline LDL-C (70 mg/dL vs. <70 mg/dL) were less likely to achieve the LDL-C goal defined by either of the criteria. Thus, a higher baseline LDL-C helps to define a target group for statin therapy optimization. Care optimization should incorporate not only prescriptions of high-intensity statins which have been shown predictive of LDL-C goal achievement, but also a follow-up lipid measurement to confirm patient response, and patient motivation on adherence to statin therapy. This study has some limitations. First, this was an observational study with inherent limitations in making causal association between the measured variables. However, the findings in our study agree with previous studies, and thus this could partly argue for the validity of our conclusions. Second, the use of statins was
Please cite this article in press as: Wongsalap Y, Jedsadayanmata A. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome. J Cardiol (2019), https://doi.org/10.1016/j.jjcc.2019.08.012
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based on prescription data in the medical database; therefore, we could not ascertain whether patients have taken statins as prescribed, this plausibly being one of the reasons for not achieving LDL-C goal. A recent study reported a low adherence to high-intensity statin therapy among patients discharged with MI [34], and thus it is conceivable that the low adherence rate could contribute to the suboptimal LDL-C goal achievement in our study. Finally, we recruited ACS patients from a single tertiary-care, teaching hospital; therefore, generalization of the findings to other settings requires further confirmation. Conclusions In a more recent cohort of Thai ACS patients, a higher proportion of patients received high-intensity statin therapy before discharge. However, the proportion of patients who achieved LDL-C goal did not increase accordingly. Several factors are identified as predictors of high-intensity statin therapy and LDL-C goal achievement. These predictors may be useful in planning to optimize statin therapy for ACS patients. Our findings should promote more discussion among health policy makers to improve statin treatment and quality of care for ACS patients. Funding This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors. Disclosures The authors declare that there is no conflict of interest. References [1] Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670–81. [2] Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012;380:581–90. [3] Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889–934. [4] Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2016;37:2999–3058. [5] Navarese EP, Kowalewski M, Andreotti F, Van Wely M, Camaro C, Kolodziejczak M, et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol 2014;113:1753–64. [6] Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001;285:1711–8. [7] Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495–504. [8] Javed U, Deedwania PC, Bhatt DL, Cannon CP, Dai D, Hernandez AF, et al. Use of intensive lipid-lowering therapy in patients hospitalized with acute coronary syndrome: an analysis of 65,396 hospitalizations from 344 hospitals participating in get with the Guidelines (GWTG). Am Heart J 2010;160:1130–6. [9] Melloni C, Shah BR, Ou FS, Roe MT, Smith Jr SC, Pollack Jr CV, et al. Lipidlowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: results from the medications applied and sustained over time (MAINTAIN) registry. Am Heart J 2010;160:1121–9. e1. [10] Praipaisarnkit K, Wongpraparut N, Pongakasira R. Low-density lipoprotein cholesterol goal attainment among post myocardial infarction patients on lipid lowering therapy at Siriraj Outpatient Clinic. J Med Assoc Thai 2014;97:S147–54.
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