Lipid lowering agent prescription and LDL target achievement in ACS patients in Jeddah, Saudi Arabia

Background: The safety and efficacy of statins administered early to patients after an acute coronary syndrome (ACS) diagnosis have been proven. This study aimed to estimate the prevalence of compliance with guideline recommendations for high-intensity dose statins and achievement of reduced low-density lipoprotein (LDL) levels among patients with ACS in Saudi Arabia. Methods: A cross-sectional study was conducted on 566 patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Data on the patient’s demographics, comorbidities, type of ACS, lipid profile at admission, statin type, statin use pattern, side effects, and if the patient achieved the low-density lipoprotein cholesterol (LDL-C) goal (70 mg/dl) or (3.9 mmol/l) after management were collected. Results: At admission, 34.1% had an LDL-C level below 100 mg/dl, 64.5% had total cholesterol below 200 mg/ dl, 57.2% had an average triglyceride level, and 53.7% had high-density lipoprotein cholesterol below 40 mg/dl. Moreover, 91% of patients consumed high-potency statins, 99.1% had no statin side effects, and atorvastatin 20 mg was the most commonly used high-potency statin, followed by atorvastatin 40 mg. Approximately 83% of patients achieved the LDL-C goal (70 mg/dl) after management, and patients who had diabetes mellitus, familial hyperlipidemia, or obesity, who experienced no side effects of statins, who had ST-segment elevation myocardial infarction, had an LDL-C level of 160-189 mg/dl at admission and those who had a high total cholesterol level at admission had a significantly higher level of achieving the LDL-C goal. Conclusions: In patients with congenital heart disease, lipid management could be improved to reduce the risk of recurrent cardiovascular disease and recurring episodes.


Introduction
Cardiovascular disease (CVD) is the leading cause of death worldwide, responsible for 17.9 million deaths in 2016 alone, accounting for 31% of all fatalities globally [1].According to the World Health Organization, the death rate due to CVD in the Gulf Cooperation Council was 42% by the end of 2016 [2].CVDs are a set of heart and blood vessel illnesses that include acute coronary syndrome (ACS) [1,3].ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina are all symptoms of ACS caused by a lack of coronary blood supply [4].Hypertension (HTN), diabetes mellitus (DM), dyslipidemia, obesity, abdominal obesity, and smoking have all been identified as important CVD risk factors in Saudi Arabia.Most patients had three or more risk factors, with dyslipidemia being the most frequent [5].Lipid-lowering drugs have been shown to reduce morbidity and death in patients with atherosclerosis, indicating that they can be used to prevent ischemic heart disease (IHD) in both primary and secondary prevention.
Several clinical trials have demonstrated the safety and efficacy of statins when administered early after ACS diagnosis.Statins may be beneficial in the early stages of secondary prevention and the treatment of ACS [6].Owing to their potential to lower low-density lipoprotein cholesterol (LDL-C) by 50% and effectively stabilize coronary plaque development at 12 months post-acute coronary events, high-intensity statins are among the most effective anti-atherosclerotic medications that are provided to patients after discharge.Moreover, high-intensity statin medication is more helpful than moderate or low-intensity statin therapy [7].The most recent guidelines were announced in November 2013, and instead of focusing on LDL-C, the new guidelines emphasized making statin intensity the treatment goal.According to a new randomized controlled study, when compared to low-dose statin medication, highintensity statin therapy reduces death following ACS [8].Furthermore, numerous findings have revealed that high-intensity statin therapy lowers LDL-C in persons with clinical atherosclerotic cardiovascular disease (ASCVD) more than moderate-intensity statin treatment [9].It is strongly advised to begin with high-intensity statin medication immediately after ACS diagnosis.Over half of the prescribed statins were high-intensity in four separate investigations undertaken in the United States, Switzerland, Thailand, and Saudi Arabia, with 67%, 70%, 56.3%, and 56.4%, respectively.Additionally, it was 38% in the United Kingdom [7,8,[10][11][12].
The suggested target is LDL-C 70 mg/dl or a reduction of at least 50% of baseline LDL-C between 70 and 135 mg/ dl, according to the European society of cardiology .In a prospective cohort trial conducted in Switzerland, 35% of patients met the recommended LDL-C target after 1 year, while 7% had their LDL-C levels decreased by 50%.Furthermore, a retrospective study in Thailand with 1753 participants found that 23.2% of patients achieved a 50% reduction in LDL-C within 3 months of discharge, and a higher proportion (35.1%) achieved the LDL-C threshold [10,11].
Muscle soreness and injury were the most common side effects of statin therapy and treatment cessation, occurring in 9.4% of the patients.Intensive statin therapy resulted in higher blood glucose levels and a higher DM rate than moderate dosage statin medication.Hepatotoxicity caused by statins occurred in approximately 3% of users, with the central nervous system and kidney symptoms being less common [13].After 1 year of follow-up, the discontinuation rates of high-intensity statin therapy in the UK and Switzerland were 53.7% and 6%, respectively [10,12].Saudi Arabia's 2030 goal intends to improve healthcare quality by measuring the compliance prevalence of prescribing appropriate guideline-directed statin doses.This study aimed to estimate the prevalence of compliance with guideline recommendations for high-intensity dose statins, assess the achievement of reduced low-density lipoprotein (LDL) and discontinuation of high-intensity dose statins among patients with ACS in the coronary care unit (CCU) at King Abdulaziz University Hospital (KAUH), Saudi Arabia.

Subjects and Methods
A cross-sectional study was conducted at the CCU at KAUH in Jeddah, Saudi Arabia, from July to September 2022.The inclusion criterion was patients admitted with ACS to the CCU at KAUH between January 2019 and December 2019, and the exclusion criterion was patients admitted with any other disease.Accordingly, a total of 566 patients were included in this study.The sample size was calculated (n = 377) according to the Raosoft sample size calculator.A pre-designed checklist was prepared to collect data about the patient's demographics, comorbidities (risk factors), type of ACS, lipid profile at admission, statin type, statin use pattern, and side effects experienced, and if the patient achieved LDL-C goal attainment (70 mg/dl) or (3.9 mmol/l) after management.Data were analyzed statistically usin statistical package for the social sciences version 26.Qualitative data were expressed as numbers and percentages, and the Chi-squared test (χ 2 ) was used to test the relationship between variables.Quantitative data were expressed as mean, standard deviation (Mean ± SD), and non-parametric variables were tested using the Mann-Whitney test.A p-value < 0.05 was considered statistically significant.Ethical approval for the study was obtained from the research ethics committee of KAUH, Jeddah, Saudi Arabia (Reference No 54-22).

Results
Table 1 shows that 72.8% of patients enrolled were below 65 years, 70.9% were males, and 70.8% had a non-Saudi nationality.Among them, the most common risk factors were smoking (66.8%),HTN (65%), IHD (43.3%), and DM (38.7%).The most common type of ACS was the NSTEMI (41.9%).On assessing the lipid profile at admission, 34.1% of patients had an LDL cholesterol level below 100 mg\dl or 2.6 mmol/l (Table 2).Of them, 64.5% had desirable total cholesterol (below 200 mg/dl or 5.2 mmol/l).While 57.2% had a normal triglyceride level (less than 100 mg/dl or 1.7 mmol/l), and 53.7% had a poor level of high-density lipoprotein (HDL) cholesterol (below 40 mg/dl or 1 mmol/l).Most patients received high-potency statins (91%) and of those treated with a low-potency statin, the most commonly used was Simvastatin 20 mg (Table 3).Only 1.2% had a previous intolerance to statin; the mean age at statin initiation was 55.42 ± 10.56 years.The majority (99.1%) experienced no statin side effects, and of those who received a highpotency statin, the most commonly used was atorvastatin 20 mg, followed by atorvastatin 40 mg.Most patients (53%) discontinued statin administration more than 1 year and less than 2 years after.Figure 1 shows the % of patients who achieved LDL-C goal attainment (70 mg/dl) or (3.9 mmol/l) after management was 83.4%.(3.9 mmol/l) (p = < 0.05).However, a non-significant relationship was found between achieving LDL-C goal attainment and patients' characteristics, other comorbidities, or type of ACS (p = > 0.05).As shown in Table 5, patients who experienced no adverse effects of statins had a significantly higher level of achieving LDL-C goal attainment (70 mg/dl) or (3.9 mmol/l) (p = < 0.05).Moreover, a non-significant relationship was found between achieving LDL-C goal attainment and patients' characteristics and statin type and using pattern (p = > 0.05).Figure 2 shows that patients who had STEMI as a type of ACS had a significantly higher level of achieving LDL-C goal attainment (70 mg/dl) or (3.9 mmol/l) (p = < 0.05).Figure 3 shows that patients who had an LDL-C level of 160-189 mg\dl or 4.1-4.9mmol/l at admission had a significantly higher level of achieving LDL-C goal attainment (70 mg/dl) or (3.9 mmol/l) (p = < 0.05).Figure 4 shows that patients who had a high total cholesterol level at admission (240 mg/dl and above or above 6.2 mmol/l) had a significantly higher level of achieving LDL-C goal attainment (70 mg/dl) or (3.9 mmol/l) (p = < 0.05).

Discussion
Our study revealed that most patients with ACS were under 65 years, consistent with earlier studies that reported that their mean age was 64.4 years [14,15].The majority of the patients in our study (70.9%) were men, which is in line with results from other studies in which 60% of participants were men (2) and 77% of participants were men in another study [16].This work revealed that smoking posed a significant risk to patients with ACS (66.8%).In contrast, another study indicated that these patients' most common risk factor was having DM (67.3%) [17].According to the findings of a 2015 study by Chinwong et al., [15] HTN was the primary risk factor, accounting for 60% of cases.The current study showed that NSTEMI (41.9%) was the most common kind of ACS, which is similar to the studies by Al Sifri et al. [17] and Chinwong et al. [15] where STEMI was the most common type of ACS 65% and 55%, respectively.The true advantages of various statins in lowering the risk of coronary heart mortality have been     demonstrated by increasing evidence over the past two decades.Additionally, several sizable clinical trials have repeatedly shown that statins may contribute significantly to both primary and secondary prevention [16].According to our findings, 91% of the patients were given highintensity statins, which is consistent with the results of another study [15].The most widely utilized medication was atorvastatin, supported by three trials that produced the same outcomes [15,17,18].According to a prior study In West China Hospital from 2008 to 2014, 58.8% of patients with a discharge diagnosis of ASCVD received statin prescriptions.Its rate is generally 10%-20% lower than in Western or wealthy countries [19].The mean age at statin initiation in our study was 55.42 ± 10.56 years, while it was 60.53 ± 12.89 in another study [20].Our patients who achieved LDL-C goal attainment (70 mg/ dl) or (3.9 mmol/l) after management were recorded as 83.4%.This result is significantly higher than that from a study by Alwhaibi et al. [14], which showed that 42% of the patients met their LDL-C target.Additionally, it was    higher than the 44% indicated in a study by Parris et al. [21].
Between 2013 and 2014, multicenter observational research was conducted on 737 patients with congenital heart disease (CHD) in Saudi Arabia.The study discovered that patients with stable CHD or ACS had poor attainment of acceptable LDL-C values.There is much room to intensify the treatment for these people at very high risk because the statin intensity was low [17].According to another analysis, the target LDL-C values are unmet throughout the Middle East region.Additionally, even with appropriate care, high-risk individuals are frequently overlooked [22].After the first year of follow-up in the current study, 34% of patients who got statins stopped taking their prescriptions.Rea et al., [23] came to a similar conclusion, which states that: after 2.4 years, 31.7% of patients stopped taking their medicine.According to this study, patients with DM, familial hyperlipidemia, or obesity included people with significantly higher levels of meeting their LDL-C target.Additionally, individuals who did not experience statin side effects had high total cholesterol or a high LDL cholesterol level upon admission and significantly higher LDL-C goal attainment than those who did not.
According to a prior study, individuals with greater cholesterol levels before admission were more likely to fall short of their lipid level goals.In the current study, there was no association between patients' characteristics, other comorbidities, or the type of ACS and meeting the targetted values of LDL-C goals.According to several studies, patients taking statins when presenting with ACS were less likely to have a myocardial infarction or develop in-hospital ischemic squeal [24][25][26].However, other studies found that prescribing discharged patients with ACS fewer than four evidence-based therapies was associated with a higher likelihood of failing to meet lipid goals.As reported in other studies, these findings suggest a more comprehensive association between the failure to provide evidence-based care and insufficient lipid-lowering therapy treatment [27][28][29].The limitation of this study is that it is a single-center study, which can hinder the generalization of the revealed results.

Conclusion
This

Table 4
shows that patients who had DM, Familial hyperlipidemia, or obesity had a significantly higher level achieving LDL-C goal attainment (70 mg/dl) or

Table 1 .
Distribution of studied patients according to their characters, comorbidities and type of acute coronary syndrome (ACS) (No.:566).

Table 2 .
Distribution of studied patients according to their lipid profile at admission (n: 566).

Table 3 .
Distribution of studied patients according to stain type, stain using pattern and side effects (n: 566).

Table 5 .
Relationship between LDL-C goal attainment (70 mg/dl) or (3.9 mmol/l) after management and statin type, stain using pattern and side effects (n: 566).
study found that at admission, 34.1% had an LDL cholesterol level below 100 mg/dl, 64.5% had total cholesterol below 200 mg/dl, 57.2% had a normal triglyceride level, and 53.7% had HDL cholesterol below 40 mg/dl.Moreover, 91% of patients had high-potency statins, 99.1% had no statin side effects, and atorvastatin 20 mg was the most commonly used high-potency statin, followed by atorvastatin 40 mg.Furthermore, 83.4% of patients achieved LDL-C goal attainment (70 mg/dl) after management.Patients with DM, familial hyperlipidemia, or obesity, who had no side effects of statins, who had STEMI, who had an LDL cholesterol level at the admission of 160-189 mg/dl and who had a high total cholesterol level at admission had a significantly higher level of achieving LDL-C goal attainment.Therefore, lipid therapy could be optimized (e.g., dose escalation, medication combinations, innovative medicines) to enhance outcomes in patients with CHD with an elevated risk of recurrent CVD and episodes.