Lipid-Lowering Therapy and Low-Density Lipoprotein Cholesterol (LDL-C) Goal Achievement in High-Cardiovascular-Risk Patients in Fuzhou,China

Abstract

Purpose:

This study aims to analyze the treatment patterns and goal attainment of low-density lipoprotein cholesterol (LDL-C) among patients with atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus (DM) in the real-world setting in Fuzhou, China.

Methods:

Patients aged ≥20 years with a valid LDL-C measurement (index date) in 2016 were selected from National Healthcare Big Data in Fuzhou, China. Patients were stratified into mutually exclusive cardiovascular risk categories: ASCVD (including recent acute coronary syndrome [ACS], chronic coronary heart disease [CHD], stroke, and peripheral arterial disease [PAD]), and DM alone (without ASCVD). Lipid-modifying medication and LDL-C attainment at the index date were assessed.

Results:

A total of 21 989 patients met the inclusion criteria, including 17 320 (78.8%) with ASCVD and 4669 (21.2%) with DM alone; 47.7% of patients received current statin therapy in the overall cohort (53.5% in ASCVD, 26.5% for DM); 20.5% ASCVD population achieved LDL-C target with the highest in patients with recent ACS (33.8%), followed by chronic CHD (21.2%), PAD (20.9%), and ischemic stroke (17.3%); 49.0% of patients with DM achieved LDL-C target. Higher LDL-C attainment was observed in high-intensity statin and a combination of statin and nonstatin groups. Atorvastatin was the most commonly used statin with the highest LDL-C attainment, followed by rosuvastatin.

Conclusion:

Compared with previous studies in China, our study found a relatively low statin use and LDL-C target attainment, but higher than similar studies in Europe. Guidelines should be well complied and more prescription of high-intensity statin or statin and nonstatin combination should be advocated.

Keywords

preventive cardiology LDL-C statin real-world evidence China

Introduction

Cardiovascular diseases (CVDs) are the single largest cause of mortality in the world,¹ accounting for more than 40% of deaths in China.² Although age-standardized mortality rates for CVDs in China have declined between 1990 and 2016, the prevalence of age-standardized CVDs increased by 14.7% and prevalent cases of CVD doubled since 1990, reaching nearly 94 million in 2016.^3,4 Reducing low-density lipoprotein cholesterol (LDL-C) levels with statin therapy has been shown to reduce all-cause mortality and the occurrence of major cardiovascular outcomes among patients with and without atherosclerotic cardiovascular disease (ASCVD).^5

-8 The Dyslipidemia International Study (DYSIS)-China showed that the achievement rate of LDL-C target (<1.8 mmol/L) was 26.1% in very high risk (having acute coronary syndrome [ACS], ischemic stroke or coronary heart disease [CHD] plus diabetes mellitus [DM]) patients with metabolic syndrome and 27.4% in patients without metabolic syndrome.⁹ Various studies had been carried out in the European countries on the lipid management among very high-risk population, the LDL-C achievement of less than 1.8 mmol/L was 13.9% in French,¹⁰ 8.5% in Germany¹¹ among population with ASCVD, and 16.0% in Italian among overall ASCVD and DM cohort.¹²

Statins are currently the first choice for lipid-lowering therapy (LLT). Their effectiveness and safety in reducing secondary coronary artery events have been fully demonstrated.^6,13
-15 Furthermore, high-intensity statin therapy is more effective than traditional therapy in lowering LDL-C level and improving cardiovascular risk.^16

-19 Low-density lipoprotein cholesterol is the primary intervention target for LLT.⁴ Guidelines for the prevention and treatment of adult hyperlipidemia in China (2016 Revision) show that LDL-C <1.8 mmol/L (<70 mg/dL) or a ≥50% reduction from baseline LDL-C would be the target for patients with very high cardiovascular risk (defined as established ASCVD).²⁰ For patients with high cardiovascular risk (defined as LDL-C ≥4.9 mmol/L or total cholesterol [TC] ≥7.2 mmol/L; patients with DM (LDL-C at 1.8-4.9 mmol/L [or TC 3.1-7.2 mmol/L] and age ≥40 years old); a 10-year risk ASCVD ≥10%), LDL-C treatment targets were < 2.6 mmol/L (<100 mg/dL) or a 30% reduction from baseline LDL-C.²⁰

Literature describing the use of statins and the achievement of lipid targets in patients with high-risk CVD in China is limited.^21,22 Using electronic medical record (EMR) in Fuzhou, we aim to reveal the status of statin used in LLT and the achievement of LDL-C target in the Chinese population within ASCVD: recent ACS, chronic CHD, ischemic stroke, peripheral arterial disease (PAD), and DM.

Methods and Material

Data Source and Study Population

A retrospective cross-sectional study was performed by retrieving data from an existing electronic health record database (National Healthcare Big Data, Fuzhou, China). This database contains over 23 million patients (from September 2001 to January 2018 in 37 hospitals) with more than 2 billion medical records in this city. These data sets contain the major clinical information systems such as hospital information system, laboratory information management system, EMR, picture archiving and communication systems, surgical information, and medical record information.

Based on the unified database platform, the clinical information data adopt the platform management, including the data processing and operation services of the IIIa hospitals, so as to realize the structured and standardized integrated management. In addition to the above data sources, Synyi artificial intelligence company employs natural language processing techniques on diagnosis and structured data from EMR. Diagnostic and clinical data are coded using International Classification of Diseases, 10th Revision Procedure Coding System. Recent ACS was defined as myocardial infarction (MI) or unstable angina requiring hospitalization within the 12 months before the index date. Chronic CHD was defined as a history of MI or unstable angina >12 months prior to the index date and within the baseline period, stable angina, coronary revascularization, or other chronic ischemic heart disease. Ischemic stroke was defined as a history of ischemic stroke within 1 year prior to the index date. Peripheral arterial disease was defined as peripheral vascular disease by noncoronary atherosclerotic disease, abdominal aortic aneurysm, and carotid artery stenosis within 1 year prior to the index date. Diabetes mellitus included both type 1 DM and type 2 DM within 1 year. This study was approved by China Ethnic Committee of Registering Clinical Trials (ChiECRCT-20190003). All procedures performed in the study conform to the ethical guidelines of the 1975 Declaration of Helsinki. The present study retrospectively analyzed data abstracted from the medical chart and national health database; thus, informed consent was not required.

Inclusion criteria were age ≥20 years; at least 1 valid LDL-C measurement in 2016, the last measurement day was defined as the index date; ≥1 high/very-high CV risk condition; and ≥2 years enrollment in the database.

Lipid-Lowering Therapy

Patients with evidence of drug prescription record within 30 days before the index date were considered as receiving current LLT. Patients with a prescription for LLT more than 30 days before the index date within 2 years were considered the previous LLT. Patients with no evidence of any drug prescription were considered no LLT. Lipid-lowering therapies were classified into statins LLT (individual or combined use of other drugs) and nonstatins LLT. Furthermore, statins LLT were stratified into high-intensity statins LLT (atorvastatin ≥40 mg once dose, rosuvastatin ≥20 mg once dose, and simvastatin ≥80 mg once dose), and low- to moderate-intensity statins (all other statins and doses). Nonstatin LLT included ezetimibe, niacin (nicotinic acid), fibrates (gemfibrozil, fenofibrate, fenofibric acid, ciprofibrate, and bezafibrate), and bile acid sequestrants (cholestyramine, colesevelam, and colestipol). The treatment pattern was considered high-intensity therapy if only one record of high-intensity statin LLT was available.

Statistical Analysis

Demographic and clinical characteristics, the most recent LLT drug use before the index date, LLT utilization among each type of ASCVD, and stratified LDL-C levels were summarized via proportions and mean ± standard deviation (SD), as appropriate. All analyses were conducted with SAS software, version 9.4 (SAS Institute, Cary, North Carolina).

Results

Patient Demographics and Clinical Characteristics

Overall, 21 989 patients met the inclusion criteria (Supplemental Figure 1.), including 17 320 (78.8%) patients with ASCVD and 4669 (21.2%) patients with DM alone. Specifically, the patients with ASCVD-stratified classification were 346 (1.6%) ACS, 12 498 (56.8%) chronic CHD, 4285 (19.5%) ischemic stroke, and 191 (0.9%) PAD. The mean (SD) age of patients included in this study was 68.8 ± 12.2 years in the whole cohort and ranged from 61.9 ± 12.4 years in patients with DM to 70.8 ± 11.4 years in patients with chronic CHD. The mean (SD) LDL-C ranged from 2.39 ± 1.09 mmol/L in patients with ACS to 2.73 ± 0.99 mmol/L in patients with ischemic stroke (Table 1).

Table 1.

Baseline Characteristics for the Overall Study Cohort and Hierarchical CV Risk Subgroups.

Characteristics	Total Cohort, N = 21 989	ASCVD, n = 17 320				DM Alone, n = 4669
Characteristics	Total Cohort, N = 21 989	Recent ACS, n = 346	Chronic CHD, n = 12 498	Stroke, n = 4285	PAD, n = 191	DM Alone, n = 4669
Age >80(%)	19.6	27.7	25.2	22.1	13.1	7.9
Age, mean (SD)	68.8 (12.2)	70.8 (13.0)	70.8 (11.4)	69.9 (11.4)	63.0 (14.3)	61.9 (12.4)
Male (%)	52.5	49.4	51.5	53.6	47.1	54.7
LDL-C (mmol/L), mean (SD)	2.68 (1.02)	2.39 (1.09)	2.67 (1.05)	2.73 (0.99)	2.65 (0.98)	2.69 (0.98)
Prevalent CV risk conditions, %
Recent ACS	1.6	100
CHD	58.0	76.3	100
Ischemic stroke	33.2	15.9	23.6	100
PAD	2.6	3.8	2.4	1.4	100
Diabetes	38.4	27.5	24.3	13.8	28.8	100
Comorbidities, %
Hypertension	61.3	61.8	70.2	46.3	49.7	51.8
History of CHF	12.4	30.3	18.8	3.6	4.2	2.4
Chronic kidney disease	1.1	2.3	1.1	0.4	2.6	1.7
COPD	7.0	9.2	9.5	3.6	3.7	3.4
Moderate/severe liver disease	15.2	17.6	15.3	8.9	16.8	20.6
Hyperlipidemia	19.7	19.7	24.1	11.5	22.5	15.2

Abbreviations: ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CHD, coronary heart disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; DM, diabetes mellitus; LDL-C, low-density lipoprotein cholesterol; PAD, peripheral arterial disease; SD, standard deviation.

Lipid-Lowering Utilization

Total cohort

Overall, 48.5% of patients were prescribed LLT within 30 days prior to the index date; 47.7% of patients received statins (3.6% high-intensity statins and 44.2% low- to moderate-intensity statins); 0.8% received nonstatin LLT (Table 2). A total cohort of 19.4% had evidence of prior LLT (but not currently treated); 32.1% of the patients had no evidence of prior LLT.

Table 2.

Use of LLT Overall and By Hierarchical Disease Categories.

%	Total Cohort, N = 21 989	ASCVD, n = 17 320				DM Alone, n = 4669
%	Total Cohort, N = 21 989	Recent ACS, n = 346	Chronic CHD, n = 12 498	Stroke, n = 4285	PAD, n = 191	DM Alone, n = 4669
Currently treated with high-intensity statin	3.6	26.0	2.8	7.2	0.5	1.0
Monotherapy	95.8	100.0	98.6	91.3	100.0	97.9
Plus other nonstatin LLT	4.2	0.0	1.4	8.7	0.0	2.1
Currently treated with low- to moderate-intensity statin	44.2	52.9	47.9	53.3	32.5	25.5
Monotherapy	98.1	98.9	98.4	98.0	98.4	97.1
Plus other nonstatin LLT	1.9	1.1	1.6	2.0	1.6	2.9
Currently treated with nonstatin LLT only	0.8	0.0	0.8	0.4	1.0	1.0
Evidence of prior LLT	19.4	11.8	22.1	16.0	11.5	16.0
High-intensity statin	9.2	39.0	9.9	5.5	9.1	8.3
Low- to moderate-intensity statin	89.3	61.0	88.6	93.9	86.4	87.9
Nonstatin LLT	1.6	0.0	1.5	0.6	4.5	3.8
No evidence of LLT	32.1	9.2	26.4	23.1	54.5	56.5

Abbreviations: ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CHD, coronary heart disease; DM, diabetes mellitus; LLT, lipid-lowering treatment; PAD, peripheral arterial disease.

Atherosclerotic cardiovascular disease population

Among patients with ASCVD, 54.2% of the patients were prescribed any LLT as of the index date within 30 days (4.3% high-intensity statins, 49.2% low- to moderate-intensity statins, and 0.7% nonstatin LLT). 20.3% of the patients were prescribed prior LLT and 25.5% of the patients had no evidence of any LLT prescription within 2 years before the index date. The current statin treatment rate (78.9%) was the highest among patients with recent ACS, followed by stroke (60.5%), chronic CHD (50.7%), and PAD (33.0%). Patients with recent ACS also had the highest high-intensity statin treatment rate both in the current treatment (26.0%) and prior treatment (39.0%). Chronic CHD had the highest proportion of prior LLT (22.1%; Table 2).

Diabetes mellitus alone

Only 27.5% of the patients with DM alone received LLT treatment, 1.0% were high-intensity statin treatment and 25.5% were low- to moderate-intensity statin treatment (Table 2). Also, 56.5% had no evidence of prior LLT (Table 2).

Low-Density Lipoprotein Cholesterol Goal Attainment (2011 Chinese Adult Dyslipidemia Prevention Guidelines)

Total cohort

The mean (SD) LDL-C was 2.68 (1.02) mmol/L in the total cohort at the index date (Table 1); 19.9% and 50.6% of the overall patients achieved LDL-C target of <1.8 and <2.6 mmol/L, respectively; 26.6% of patients at high or very high risk achieved the LDL-C attainment.

The goal achievement of LDL-C < 1.8 mmol was higher among currently prescribed with high-intensity statin and low- to moderate-intensity statin (26.4% and 25.6%, respectively), the other 3 groups (currently prescribed with nonstatin prescription, previous LLT, and no evidence of LLT) had a relatively lower goal achievement of about 15%. The same result was obtained among patients with LDL-C <2.6 mmol/L (Table 3).

Table 3.

Achievement of Lipid Goals by Cardiovascular Risk Category and Treatment Type.

%	Total Cohort, N = 21 989	ASCVD, n = 17 320				DM Alone, n = 4669
%	Total Cohort, N = 21 989	Recent ACS, n = 346	Chronic CHD, n = 12 498	Stroke, n = 4285	PAD, n = 191	DM Alone, n = 4669
LDL-C <1.8 mmol/L	n = 4372	n = 117	n = 2648	n = 743	n = 40	n = 824
Currently prescription with high-intensity statin	26.4	24.4	31.9	18.8	0.0	40.4
Currently prescription with low- to moderate-intensity statin	25.6	35.0	27.7	20.2	27.4	23.6
Currently prescription with nonstatin prescription	15.7	/	14.3	23.5	0.0	16.3
Previous LLT	14.2	46.9	12.8	12.6	19.2	16.1
No evidence of LLT	15.2	39.0	15.9	14.0	13.6	12.2
LDL-C <2.6 mmol/L	n = 11 124	n = 219	n = 6453	n = 2062	n = 98	n = 2292
Currently prescription with high-intensity statin	58.9	52.2	65.5	51.8	100.0	68.1
Currently prescription with low- to moderate-intensity statin	57.0	68.9	59.5	50.9	61.3	54.0
Currently prescription with nonstatin prescription	41.6	/	36.7	64.7	0.0	44.9
Previous LLT	45.3	68.8	42.6	44.4	48.1	48.5
No evidence of LLT	43.6	58.5	44.2	42.2	40.9	42.2
LDL-C ≥2.6 mmol/L	n = 10 865	n = 127	n = 6045	n = 2223	n = 93	n = 2377
Currently prescription with high-intensity statin	41.1	47.8	34.5	48.2	0.0	31.9
Currently prescription with low- to moderate-intensity statin	43.0	31.1	40.5	49.1	38.7	46.0
Currently prescription with nonstatin prescription	58.4	/	63.3	35.3	100.0	55.1
Previous LLT	54.7	31.3	57.4	55.6	51.9	51.5
No evidence of LLT	56.4	41.5	55.8	57.8	59.1	57.8

Abbreviations: ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CHD, coronary heart disease; DM, diabetes mellitus; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering treatment; PAD, peripheral arterial disease.

Atherosclerotic cardiovascular disease population

Among ASCVD population, LDL-C goal achievement of less than 1.8 mmol/L was highest in patients with recent ACS (33.8%), followed by chronic CHD (21.2%), PAD (20.9%), and ischemic stroke (17.3%). Mean LDL-C of patients with recent ACS was also the lowest among patients with ASCVD (Table 1). The proportion of patients with 1.8 mmol/L < LDL-C < 2.6 mmol/L varied little among stratified patients with ASCVD (Table 3).

Diabetes mellitus alone

Among patients with DM alone, mean (SD) LDL-C was 2.69 (0.98) mmol/L for patients at the index date. Goal achievement of LDL-C < 1.8 and <2.6 mmol/L was 17.6% and 49.0%, respectively. The target achievement (LDL-C < 2.6 mmol/L) rate of high-intensity statin treatment was notably higher than that of low- to moderate-intensity statin treatment (68.1% vs 54.0%; Table 3).

Low-Density Lipoprotein Cholesterol Goal Achievements by Treatment Pattern and Statin Type

The average level of LDL-C in statin-treated high-risk and very high-risk patients was significantly lower than that in the past treatment group and nontreatment group. Among the current statin treatment groups, combined statin was associated with lower LDL-C average level and higher LDL-C target achievement (<1.8 mmol/L) compared with monostatin therapy (Table 4).

Table 4.

LDL-C Goal Achievements By Treatment Pattern.

LDL-C (%)	Currently Treated With High-Intensity Monostatin (n = 762)	Currently Treated With Low- to Moderate-Intensity Monostatin (n = 9533)	Currently Treated With High-Intensity Combined Statin (n = 33)	Currently Treated With Low- to Moderate-Intensity Combined Statin (n = 180)	No Evidence of LLT (n = 7060)	Evidence of Prior LLT With High-Intensity Statin (n = 391)	Evidence of Prior LLT Without High-Intensity Statin (n = 3864)
Mean (SD), mmol/L	2.50 ± 0.99	2.56 ± 1.03	2.41 ± 0.93	2.36 ± 1.02	2.79 ± 0.98	2.74 ± 1.07	2.84 ± 1.02
<1.8 mmol/L	26.2	25.4	30.3	37.8	14.2	21.5	14.5
1.8-2.6 mmol/L	32.8	31.5	24.2	23.9	31.0	26.9	28.6
>2.6 mmol/L	40.9	43.1	45.5	38.3	54.7	51.7	56.9

Abbreviations: Combined statin, combination of statin and nonstatin; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering treatment; SD, standard deviation.

Atorvastatin group had the lowest average level of LDL-C (2.45 ± 0.98 mmol/L) and the highest goal achievement both in LDL-C < 1.8 mmol/L (28.4%) and in LDL-C < 2.6 mmol/L (61.2%). Rosuvastatin group followed closely with the second lowest average level of LDL-C (2.57 ± 1.08 mmol/L) and the second highest goal achievement both in LDL-C <1.8 mmol/L (26.9%) and in LDL-C <2.6 mmol/L (57.1%; Table 5).

Table 5.

LDL-C Goal Achievements By Statin Type.

LDL-C (%)	Total Statin, n = 10 295	Atorvastatin, n = 4209	Rosuvastatin, n = 3344	Fluvastatin, n = 1540	Pravastatin, n = 781	Simvastatin, n = 418	Lovastatin, n = 3
Mean (SD), mmol/L	2.55 ± 1.03	2.45 ± 0.98	2.57 ± 1.08	2.74 ± 0.99	2.63 ± 0.98	2.67 ± 1.15	3.21 ± 0.70
<1.8 mmol/L	25.4	28.4	26.9	17.5	20.4	22.5	0.0
1.8-2.6 mmol/L	31.6	32.8	30.2	31.7	33.0	28.2	33.3
>2.6 mmol/L	42.9	38.8	42.9	50.8	46.6	49.3	66.7

Abbreviations: LDL-C, low-density lipoprotein cholesterol; SD, standard deviation.

The Latest Medication Type Among Patients With Current LLT

Among patients with current LLT, atorvastatin (40.0%) was the most commonly prescribed lipid-lowering drug, followed by rosuvastatin (31.6%), fluvastatin (14.5%), pravastatin (7.4%), and simvastatin (3.9%). The treatment rate of atorvastatin in patients with recent ACS was much higher than that in other patients with ASCVD and DM alone (Supplemental Table 1).

Discussion

This study summarized the use of lipid-lowering drugs among patients with ASCVD and DM in China in 2016 and evaluated the target achievement of LLT for different types of treatment patterns and diseases. Although Chinese and European guidelines strongly recommend statins for the treatment of high-risk cardiovascular patients,^4,23 our study found that only 53.5% of patients with ASCVD and 26.5% of patients with DM were prescribed statins within 30 days prior to the index date. These findings highlight the huge gap between clinical practice in the real world and existing practice guidelines.^4,23

Compared with similar studies in European countries,^24,25 we observed relatively low prescription rates of lipid-lowering drugs in patients at high or very high risk of CVD. Despite the heavy burden of CVD in China,² 25.5% of patients with ASCVD and 56.5% of patients with DM alone did not receive any LLT within 2 years prior to the index date. Besides, this study found that only 3.6% of patients with ASCVD and 1.0% of patients with DM alone received high-intensity statin therapy within 30 days prior to the index date. It may be related to the recommendation that moderate-intensity statin should be used at the beginning of clinical treatment for the sake of medication safety in Guidelines for the Prevention of Cardiovascular Diseases in China.⁴

The Chinese guidelines for the prevention of CVDs point out that statins are the first choice for LLT at present. Relevant studies have shown that the statin use rate in China has increased in recent years.²⁶ A survey of 1.7 million people in China shows that 9.5% of respondents are at high risk of CVD. Only 0.6% of the respondents in the high-risk cardiovascular group took statins for secondary prevention.²⁷ Another hospital-based study including 51 972 patients found that 58.8% of the discharge diagnosed patients with ASCVD were prescribed statins between 2008 and 2014, which is consistent with 53.5% current statins prescription rate among patients with ASCVD in our study.²⁶

In this study, ACS was associated with the highest statin use. The Improving Care for Cardiovascular Disease in China (CCC)-ACS project between 2014 and 2017 demonstrated that 33.9% and 12.7% of patients with ACS with and without a history of ASCVD had been prescribed statins before hospitalization.²⁸ Another study from the Improving Care for Cardiovascular Disease in China project found that 50.8% of patients with ACS with a history of MI or revascularization were receiving LLT before hospitalization (statin monotherapy in 98.4%, combination in 1.2%). The proportion of patients receiving statin monotherapy reached 91.8%, of which 90.7% were at moderate doses.²⁹ The CCC-ACS project found that the statin prescription rate of patients with non-ST-segment elevation ACS before discharge was 93%.³⁰ One previous study in 14 large comprehensive hospitals in Beijing shows that 96.3% of patients diagnosed with acute myocardial infarction were prescribed statin²² and 80.5% of the patients discharged alive from 53 hospitals across China were prescribed statins.³¹ These studies show that for the same group of patients with the same disease, statin treatment rates may vary greatly due to different research designs and procedures. Generally speaking, the prescription rate for statins in the hospital is much higher than that before admission. At the same time, the utilization rate of statin in population epidemiological survey is much lower than that in the hospital-based study. Different criteria for classifying high-risk CVD groups may be the main reason for the above differences. Besides, recall bias and disease concealment in epidemiological surveys, severe illness, more attention on self-health care among patients in the hospital are all potential reasons for different statins utilization as secondary prevention in high-risk CVD groups.

About 82% of patients with CHD discharged from 52 hospitals in 6 cities in China received statin treatment between 2006 and 2007.³² The statin treatment rate of patients with PAD was much lower than that of patients with CHD (61% vs 22%), which is consistent with our findings.³³

Research from China National Stroke Registry shows that 43.6% of patients with ischemic stroke without a history of prestroke statin treatment were receiving statins during hospitalization after stroke.³⁴ For patients with noncardiogenic ischemic stroke or transient ischemic attack, long-term treatment with high-intensity statins is recommended to reduce the risk of stroke and cardiovascular events, regardless of other evidence of atherosclerosis. It is recommended that LDL-C be reduced to less than 1.8 mmol/L (70 mg/dL).⁴ Our study also found that patients with stroke had a current statin treatment rate of 60.5% (7.2% high-intensity statin), followed by only to patients with ACS among all patients with ASCVD.

Research from 11 community hospitals in Nanjing between 2005 and 2014 shows that 20.9% of patients with DM without CVD history took statins for LDL-C management, which is very close to the result of 26.5% in our study.

The recommendation of moderate-intensity statins for the primary treatment in the Chinese Guidelines may be the underlying cause of the low achievement rate of China’s LDL-C target. Only 20.5% of the patients with ASCVD and 17.6% of the patients with DM alone achieved the LDL-C target of less than 1.8 mmol/L. About 49.0% and 50.9% of the patients with ASCVD and DM alone fail to achieve the target of LDL-C less than 2.6 mmol/L, respectively. Other studies showed similar or higher compliance rate with regard to LDL-C target achievement. For example, 24.7% of patients with ACS with a history of ASCVD achieved the LDL-C target of less than 1.8 mmol/L.²⁸ The CCC in China project indicated that 30.1% of patient with ACS had LDL-C <70 mg/dL at admission.²⁹ Diabetic patients of 38% met the target goal and 37.3% of patients who took lipid-lowering agents met LDL-C target goal in 11 hospitals in Naniing.³⁵

Similar studies on statins utilization and LDL-C achievement among patients with ASCVD and DM alone have been conducted in several European countries, but few have been conducted in Asia. The LDL-C achievement of less than 1.8 mmol/L was 13.9% in French,¹⁰ 8.5% in Germany¹¹ among ASCVD population, and 16.0% in Italian among the overall cohort.¹² Our result of 26.6% attainment in the overall cohort or 20.5% in the patients with ASCVD shows that our lipid control among high-risk population was better than that in Europe, despite relatively low prescription rates of lipid-lowering drugs. The global DYSIS throughout 30 countries worldwide also demonstrated better performance on LDL-C target achievement in China compared with the Europe/Canada/Israel group (31.4% vs 24.7%).³⁶ However, it must be noted that the basal cholesterol levels in Chinese population are much lower than that in the Europeans.

In terms of the latest drug use, atorvastatin was the most frequently used statin, followed by rosuvastatin, fluvastatin, pravastatin, and simvastatin. The atorvastatin treatment group also achieved the highest rate of lipid-lowering goals, followed by rosuvastatin. The Bayesian network meta-analysis by Lu et al also found that atorvastatin was the most effective in blood-lipid level modification as well as in reducing the risk of CHD mortality and all-cause mortality.³⁷

Studies have shown that high-intensity statin therapy is more effective in reducing lipid and cardiovascular events.^6,38 However, high-intensity statin treatment had a slightly higher risk of rhabdomyolysis³⁹ and DM⁴⁰ as well as higher rates of toxicity.⁶ Thus, the combination of statin and other lipid-lowering drugs has been extensively studied, from which they found that combination therapy is not only safer but also more effective.^41

-44 Studies have confirmed that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can be used as a new lipid-lowering drug when statin alone is ineffective for lipid lowering.^45,46 Therefore, more and more evidence show that the combination of statin and nonstatin drugs will be the key of lipid control.⁴⁷

Limitations

As the hospitals involved in this study are concentrated in Fuzhou, China, rather than nationwide sampling, the results cannot be generalized to the whole country. Secondly, the selected population is patients with LDL-C records in 2016. It cannot represent all the high-risk or extremely high-risk patients in the hospital, let alone all the population. Thirdly, guidelines for the prevention and treatment of adult hyperlipidemia in China in 2016 indicate, in addition to LDL-C numerically less than 1.8 mmol/L, also a ≥50% reduction from baseline LDL-C for patients with very high cardiovascular risk and a 30% reduction from baseline LDL-C for patients with high cardiovascular risk would meet the target achievement. As the cross-sectional study cannot measure these data, our study may underestimate the LDL-C attainment rate. Fourthly, drug use was based on doctors’ prescription, not on whether the patient actual drug-taking, so the actual drug use would be less than what we reported, and patients may be classified as exposed when they didn’t take the medicine. Finally, when comparing the frequency of different drug usage, we use the latest medication to estimate the total drug proportion. In fact, there may be drug conversion and combination, and our estimates may be biased.

Conclusion

Our study shows that there was suboptimal use of statins among patients with ASCVD and DM alone in Fuzhou, China, especially excessively small proportion use of high-intensity statins and combined medication with other nonstatins, although our study revealed that high-intensity statin and combination therapy were more effective on lipid lowering. Thus, guidelines should be well complied and more prescription of high-intensity statin or statin and nonstatin combination (including newer therapeutic options, such as PCSK9 inhibitors) should be advocated. Besides, atorvastatin should be used more widely, because it’s relatively cheaper due to the expiration of patent protection and more effective in reducing lipids and mortality.

Supplemental Material

Supplementary_file - Lipid-Lowering Therapy and Low-Density Lipoprotein Cholesterol (LDL-C) Goal Achievement in High-Cardiovascular-Risk Patients in Fuzhou, China

Supplementary_file for Lipid-Lowering Therapy and Low-Density Lipoprotein Cholesterol (LDL-C) Goal Achievement in High-Cardiovascular-Risk Patients in Fuzhou, China by Xing Wang, Yan He, Tao Wang, Chunming Li, Zihui Ma, Heng Zhang, Handong Ma and Hongxin Zhao in Journal of Cardiovascular Pharmacology and Therapeutics

Footnotes

Acknowledgment

The authors thank China Electronics Corporation (CEC) data for granting access to the National Health database.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Xing Wang

Hongxin Zhao

Supplemental Material

Supplemental material for this article is available online.

References

Sacco

Roth

Reddy

, et al. The Heart of 25 by 25: achieving the goal of reducing global and regional premature deaths from cardiovascular diseases and stroke: a modeling study from the American Heart Association and World Heart Federation. Glob Heart. 2016;11(2):251–264.

Zhou

Wang

Zhu

, et al. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet. 2016;387(10015):251–272.

Liu

Zeng

, et al. Burden of cardiovascular diseases in china, 1990-2016: findings from the 2016 global burden of disease study. JAMA Cardiol. 2019;4(4):342–352.

Guidelines for the Prevention of Cardiovascular Diseases in China Writing Group & Editorial Committee of the Chinese Journal of Cardiovascular Diseases. Guidelines for the prevention of cardiovascular diseases in China (2017). Chinese J Cardiovasc Dis. 2018;46(1):10–25.

Baigent

Keech

Kearney

, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–1278.

Baigent

Blackwell

Emberson

, 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(9753):1670–1681.

Cannon

Blazing

Giugliano

, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397.

Ling

Burns

Hilleman

. Novel strategies for managing dyslipidemia: treatment beyond statins. Postgrad Med. 2012;124(6):43–54.

Wang

, et al. Lipid-lowering therapy and lipid goal attainment in patients with metabolic syndrome in China: subgroup analysis of the Dyslipidemia International Study-China (DYSIS-China). Atherosclerosis. 2014;237(1):99–105.

10.

Ferrieres

Gorcyca

Iorga

Ansell

Steen

. Lipid-lowering therapy and goal achievement in high-risk patients from French general practice. Clin Ther. 2018;40(9):1484–1495.e22.

11.

Marz

Dippel

Theobald

Gorcyca

Iorga

ŞR

Ansell

Utilization of lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients at high and very-high cardiovascular risk: real-world evidence from Germany. Atherosclerosis. 2018;268:99–107.

12.

Arca

Ansell

Averna

, et al. Statin utilization and lipid goal attainment in high or very-high cardiovascularrisk patients: Insights from Italian general practice. Atherosclerosis. 2018;271:120–127.

13.

Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–1389.

14.

Kearney

Blackwell

Collins

, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–125.

15.

Kashani

Phillips

Foody

, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006;114(25):2788–2797.

16.

Liu

Dong

Wang

. Long-term benefits of high-intensity atorvastatin therapy in Chinese acute coronary syndrome patients undergoing percutaneous coronary intervention: a retrospective study. Medicine (Baltimore). 2018;97(42):e12687

17.

Murphy

Cannon

Wiviott

McCabe

Braunwald

. Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial. J Am Coll Cardiol. 2009;54(25):2358–2362.

18.

Cannon

Braunwald

McCabe

, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495–1504.

19.

LaRosa

Grundy

Waters

, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–1435.

20.

Joint Committee on Revision of Guidelines for Prevention and Treatment of Adult Lipid Abnormalities in China. Guidelines for prevention and treatment of adult lipid abnormalities in China (2016 revision). Chin J Health Manag. 2017;11(1):7–28.

21.

Zhang

Wang

. Factors associated with unattained LDL-cholesterol goals in Chinese patients with acute coronary syndrome one year after percutaneous coronary intervention. Medicine (Baltimore). 2017;96(1):e5469.

22.

Zhou

Yao

Liu

Jian

Yip

. Level and variation on quality of care in China: a cross-sectional study for the acute myocardial infarction patients in tertiary hospitals in Beijing. BMC Health Serv Res. 2019;19(1):43.

23.

Catapano

Graham

De Backer

, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis. 2016;253:281–344.

24.

Bauters

Tricot

Lemesle

, et al. Reaching low-density lipoprotein cholesterol treatment targets in stable coronary artery disease: determinants and prognostic impact. Arch Cardiovasc Dis. 2018;111(11):634–643.

25.

Presta

Figliuzzi

Miceli

, et al. Achievement of low density lipoprotein (LDL) cholesterol targets in primary and secondary prevention: Analysis of a large real practice database in Italy. Atherosclerosis. 2019;285:40–48.

26.

Huang

Peng

Huang

, et al. Trends in prescribing rate of statins at discharge and modifiable factors in patients with atherosclerotic cardiovascular disease. Intern Emerg Med. 2017;12(8):1121–1129.

27.

Yang

, et al. Characteristics of high cardiovascular risk in 1.7 million Chinese adults. Ann Intern Med. 2019;170(5):298–308.

28.

Xing

Liu

, et al. Statin use and low-density lipoprotein cholesterol levels in patients aged 75 years and older with acute coronary syndrome in China [in Chinese]. Zhonghua Xin Xue Guan Bing Za Zhi. 2019;47(5):351–359.

29.

Xing

Liu

Hao

, et al. Prehospital statin use and low-density lipoprotein cholesterol levels at admission in acute coronary syndrome patients with history of myocardial infarction or revascularization: findings from the improving care for cardiovascular disease in China (CCC) project. Am Heart J. 2019;212:120–128.

30.

Yang

Liu

, et al. Performance on management strategies with class i recommendation and a level of evidence among hospitalized patients with non-ST-segment elevation acute coronary syndrome in China: findings from the improving care for cardiovascular disease in China-acute coronary syndrome (CCC-ACS) project. Am Heart J. 2019;212:80–90.

31.

Shang

Liu

Zheng

, et al. Association between medication adherence and 1-year major cardiovascular adverse events after acute myocardial infarction in China. J Am Heart Assoc. 2019;8(9):e011793.

32.

. The gender differences in baseline characteristics and statin intervention among outpatients with coronary heart disease in China: the China Cholesterol Education Program. Clin Cardiol. 2009;32(6):308–314.

33.

Chen

, et al. Use of secondary preventive medications in patients with atherosclerotic diseasein urban China: a cross-sectional study of 16, 860 patients. Chin Med J (Engl). 2012;125(24):4361–4367.

34.

Zhang

Jing

Zhao

, et al. Statin use during hospitalization and short-term mortality in acute ischaemic stroke with chronic kidney disease. Eur Neurol. 2018;79(5-6):296–302.

35.

Ouyang

Zhang

Chen

Bian

. Situational analysis of low-density lipoprotein cholesterol control and the use of statin therapy in diabetes patients treated in community hospitals in nanjing, china. Chin Med J (Engl). 2018;131(3):295–300.

36.

Gitt

Lautsch

Ferrieres

, et al. Low-density lipoprotein cholesterol in a global cohort of 57,885 statin-treated patients. Atherosclerosis. 2016;255:200–209.

37.

Cheng

Zhao

, et al. Efficacy and safety of long-term treatment with statins for coronary heart disease: a Bayesian network meta-analysis. Atherosclerosis. 2016;254:215–227.

38.

Liu

Hao

, et al. Efficacy of high intensity atorvastatin versus moderate intensity atorvastatin for acute coronary syndrome patients with diabetes mellitus. Int J Cardiol. 2016;222:22–26.

39.

Ramkumar

Raghunath

. Statin therapy: review of safety and potential side effects. Acta Cardiol Sin. 2016;32(6):631–639.

40.

Navarese

Buffon

Andreotti

, et al. Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol. 2013;111(8):1123–1130.

41.

Miao

Liu

Jin

, et al. A comparative meta-analysis of the efficacy of statin-ezetimibe co-therapy versus statin monotherapy in reducing cardiovascular and cerebrovascular adverse eventsin patients with type 2 diabetes mellitus. Eur Rev Med Pharmacol Sci. 2019;23(5):2302–2310.

42.

Guo

Zhu

, et al. Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers. Lipids Health Dis. 2018;17(1):265.

43.

Liu

Xiao

. Effectiveness and safety of combinational therapy compared with intensified statin monotherapy in patients with coronary heart disease. Exp Ther Med. 2018;15(6):4683–4688.

44.

Lee

Park

Kang

, et al. Effect of atorvastatin monotherapy and low-dose atorvastatin/ezetimibe combination on fasting and postprandial triglycerides in combined hyperlipedemia. J Cardiovasc Pharmacol Ther. 2012;17(1):65–71.

45.

Sabatine

. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: comparing and contrasting guidance across the Atlantic. Eur Heart J. 2017;38(29):2256–2258.

46.

White

. The pharmacologic role and clinical utility of pcsk9 inhibitors for the treatment of hypercholesterolemia. J Cardiovasc Pharmacol Ther. 2018;23(4):301–308.

47.

Khera

Natarajan

Kathiresan

. The future of low-density lipoprotein cholesterol lowering therapy: an end to statin exceptionalism? Eur J Prev Cardiol. 2016;23(10):1062–1064.

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