Atorvastatin Utilization and Prescribing Behavior in Saudi Arabia
Corresponding author: Abdulaziz H. Alsaggabi, Drug Policy & Economics Center, King Saud Bin Abdulaziz University, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia, Email: email@example.com
Hyperlipidemia is one of the major risk factors for cardiovascular disease (CVD) and coronary heart disease (CHD) [1, 2]. Several drug classes are available for the treatments of hyperlipidemia, such as the bile acid sequestrate cholestyramine, fibrates, selective cholesterol absorption inhibitors (CAI) such as ezetimibe and most frequently, hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (‘statins’).
Strict control and management of hyperlipidemia for primary and secondary prevention of cardiovascular and other complications are recommended by all international guideline agencies especially for patients at risk [3-6]. It has been proven that the use of lipid-modifying therapies (LMT), mostly statins, has protective effects for various patient groups in clinical trials [7, 8]. Setting lower LDL cholesterol (LDL-C) targets based on individual cardiovascular risk was the most important target in the published guidelines, such as those from the Adult Treatment Panel (ATP). Over the past two decades, the shifted focus towards lowering the target level of LDL-C [3, 9]. In line with international recommendations, the current clinical practice at the National Guard Health Affairs institutions as well as other medical institutions in Saudi Arabia use a target LDL-C of <130 mg/dL (3.4 mmol/L) for medium-risk patients, <100 mg/dL (2.6 mmol/L) for high-risk patients (including patients with diabetes), and <70 mg/dL (1.8 mmol/L) for very high-risk patients (including patients with diabetes and additional risk factors) [3, 9, 10]. Furthermore, the beneficial effects of lipid-lowering drugs even in patients with normal LDL levels and the higher effectiveness of intensive statin therapy in patients with diabetes and chronic kidney disease have been reported by several important clinical studies [11, 12]. Lifestyle modification is a very essential aspect for appropriate cholesterol management and CHD risk reduction.
The explanation of statins indications beyond the secondary prevention of cardiovascular events after myocardial infarction and the proven effectiveness of intensive statin therapy resulted in a dramatic increase of satins utilization in many countries; even though, their utilization varies extensively from county to another [13-18]. Monitoring the utilization of statins is important to promote evidence-based, safe and effective and cost-effective utilization of these therapies. The increasing trend of statins utilization have been reported by several studies [14-17, 19, 20], but only a few studies have looked at trends in statin initiation [13, 21-23]. No such utilization studies were done to measure statins utilization trend and utilization in Saudi Arabia. The aim of our study was to describe trends of Atorvastatin initiation in term of patients’ characteristics and treatment patterns at King Abdulaziz Medical City in Saudi Arabia.
The data for this retrospective descriptive study was obtained from the hospital information system and chart review at King Abdulaziz Medical City (KAMC) in Riyadh, a tertiary center under the Ministry of National Guard Health Affairs (MNGHA) that provides health services to all Ministry of National Guard employees and their dependents . About 1 million persons are eligible for the KAMC’s services.
The study population was defined as all KAMC patients were first prescribed atorvastatin on September 2006. Patients were considered newly prescribed atorvastatin and therefore eligible for this study if no prescription of Atorvastatin were filled in 2004, 2005 and first eight months of 2006 according to the legacy outpatient’s prescriptions systems at KAMC. The total eligible population was 720 patients and a random sample of 300 patients was selected.
The following individual characteristics were collected: age, gender, and blood pressure/hypertension, diabetes smoking status cardiovascular disease (CVD) and chronic heart disease (CHD) or chronic heart disease equivalent (CHD equivalents – which include occlusive carotid disease, peripheral vascular disease, abdominal aortic aneurysm, or diabetes). We also collected data on the most recent lipid profile testing including (LDL-C/HDL-C and cholesterol blood levels) prior to atorvastatin therapy initiation, as determined by routine blood lipid tests. All laboratory tests were conducted in-house at the central laboratory of KAMC. Previous lipid-lowering drug use was also collected to measure the switch rate to atorvastatin and the reasons for the switch. Lifestyle modification (need for exercise or increase in activity level and/or need for nutrition modification or referral to a dietitian) and the frequency of lipid profile testing for all patients including those who have been taking other lipid-lowering drugs before starting atorvastatin have been collected. Documented physician’s recommendation to modify diet or activity level (or exercises) or documented referral or instruction for the future referral to dietitian were considered as instructions on lifestyle and diet modifications. Risk factors assessment was based on The National Cholesterol Education Program Adult Treatment Panel III (ATP III) and Institute for Clinical Systems Improvement Health Care Guidelines [25, 26].
Data were summarized descriptively as means ± standard deviation, frequencies (N and percentages) or proportions, as appropriate. Proportions of atorvastatin initiation dose were calculated by gender, age group and a number of documented risk factors, acute risk factors as well as CHD/CHD equivalents. Distribution of atorvastatin doses was described and cross-tabulated by the baseline LDL-level. The proportion of patients who were switched from previous other lipid-lowering drugs and the reason for the switch was described. The frequency of lipid profile testing for those who were on other lipid-lowering drugs before starting atorvastatin was measured. Lifestyle modification instructions by healthcare providers were described in details. Analyses were performed in SPSS version 16.0 (SPSS Inc., Chicago, IL).
Patients’ demographic information is reported in Table 1. Patients on atorvastatin were mostly female (149 [54.58%]). Participants’ age ranged primarily from 45-54 years (82 [30.04%]) followed by above 65 years (72 [26.37%]). Almost half of the patients were between 45 and 65 years (144 [52.75%]). Relatively, a small proportion of patients had reported risk factors (RF) (106 [38.83%]). However, using the measured RF, a majority of the patients had one or two RF (170 [62.26%)]. A high proportion of patients had CHD or CHD equivalents (124 [45.42%]). The CHD Equivalents cases were mainly diabetes (82 [30.04%]).
Majority of patients were initiated on atorvastatin 10 mg dose (139 [50.92%]) followed by a 20 mg dose (90 [32.97%]). In addition, the high dose atorvastatin dose (40 mg) was prescribed for only 44 patients (16.12%). A small proportion of patients were shifted from previous statin therapy (39 [13.91%]) and only 15.79% of them had a documented reason as the failure to achieve the LDL target level.
Table 1: Demographics and other characteristics patients who were on atorvastatin at the National Guard Health Affairs in 2008
Initiation of Atorvastatin Therapy
At the initiation of atorvastatin therapy, a majority of the patients (48.35%) had a moderate reduction in LDL-C level ranging from 2.59 – 4.13 mmol/L and only a small proportion of them (around 9%) of them had a very low LDL level of <1.81 mmol/L. On the other hand, Majority of the patients (45.79%) had a moderate increase in HDL-C level ranging from 1.03 – 1.54 mmol/L and most of the reaming (39.56%) had a mild increase in HDL-C level < 1.03 mmol/L. Majority of patients (47.99%) had low TG level < 1.69 mmol/L. From the CHD and CHD equivalent patient, 2 (7.41%) and 19 (70.37%), respectively, were at goal LDL-C level when atorvastatin was initiated. Refer to table-2 below for details.
Note: no other lipid lowering medications were given including Exenatide
Table 2: Description of lipid profiles at initiation of atorvastatin
The relationships between LDL-C level and atorvastatin starting dose
As illustrated in table-3 and figure-1 below, the percentage of patients who have been initiated on a high dose (40 mg) were higher in those with LDL level of <1.81 (29.17%) than patients with LDL level of 1.81-2.58 (25.71%) and patients with LDL level of 2.59-3.35 (13.64%). Out of the 38 patients who were shifted from a previous statin, (37 [97.37%]) were shifted from simvastatin and the reason was reported for 6 patients only as a failure to archive LDL goal.
Note: no other lipid lowering drugs were given including Exenatide
Table 3: Relationship between LDL-C level and atorvastatin initial daily doses
LDL-C: Low-density lipoprotein Cholesterol
Figure 1: Relationship between LDL-C Level and Atorvastatin Starting Dose
Documented instructions on lifestyle and diet modifications were only available in 23.08% of patients (63 patients). Instructions for diet modification were documented for 61 patients (22.34%) and for instructions to increase activity level for 43 patients (15.75%). The percentage of instructed patients who had CHD &CHD equivalent was higher than other patients. For these patients, instructions for diet modification were documented for 34 patients (27.42%) and for instructions to increase activity level for 47 patients (37.90%).
Table 4: Description of documented patients’ instructions on lifestyle and diet modifications
Drug utilization evaluation (DUE) that includes analysis of physician prescribing patterns in various healthcare settings is an important source of information for improving the quality of care. Registries for chronic diseases are considered important tools that provide a continuous and comprehensive source of information for DUE as they allow linking procedures and prescriptions to patient and hospital or physician characteristics and, importantly, to treatment outcomes [27-30]. This study evaluates atorvastatin utilization and measures the patterns of use at a referral institution in Saudi Arabia.
In this population, a majority of patients on atorvastatin were female (54.6%) older than 45 years (79.1%) with one or two risk factors (62.3%). This finding is consistent with Ferrajolo C. study. His study indicated that, in Italy, a majority of statins users were female (51.4%) and were older than 45 years (94.0%) .
Initiation of atorvastatin therapy and risk factors
Several variables should be considered before initiating statins therapy such as a simultaneous increase in LDL-C and TLC levels, the presence of one or more risk factors, and presence of CHD and/or CHD equivalent [29, 32-34].
This study indicated that at initiation of atorvastatin therapy, majority of the patients (48.35%) had a moderate reduction in LDL-C level ranging from 100 – 159 mg/dL (2.59 – 4.13 mmol/L) and moderate increase in HDL-C level ranging from 40– 59 mg/dL (1.03 – 1.54 mmol/L). Atorvastatin use was greater in men than in women and in older age groups. In a similar study, Simpson, R. J. et al. find that among hospitalized patient in the United States, the mean LDL-C level was 138 mg/dL (7.66 mmol/L) before statin initiation and the mean after initiation was 101 mg/dL (5.6 mmol/L) . Another real-world study in the United States settings indicated that more than 65% of the patients had LDL-C levels >70 mg/dL (>1.8 mmol/L) after statin therapy initiation regardless of dose .
Around 45% of the patients in this study who were on atorvastatin, had CHD and CHD equivalent risk factor. Among those patients, a majority (78.2%) were not on goal LDL-C when atorvastatin was initiated. Several studies have shown that much higher risk CHD and/or CHD equivalent risk patients do not achieve their guideline recommended LDL-C goals. Approximately 66% of high-risk CHD patients achieve LDL-C levels of 100 mg/dL (<2.6 mmol/L), only about one third of these patients attain LDL-C 70 mg/dL (<1.8 mmol/L) levels [34, 37, 38].
Shifting to another statin therapy
Approximately 16.21% of patients were shifted from simvastatin to atorvastatin with a clear reason for shifting to atorvastatin stated on patients’ charts. However, failure to reach LDL-C goals has been assumed to be the reason for that. Almost all shifted patients were on the maximum simvastatin dose (40 mg) before shifting to atorvastatin and were not at the goal LDL-C level. Therefore, the main reason for shifting to atorvastatin was assumed to be a failure of the current statin therapy of archiving the goal LDL-C level.
Atorvastatin dose considerations and risk factors
Simvastatin 40 mg dose is considered by many as the maximum dose due to concern for side effects with higher doses.
In this healthcare institution, among patients with high risk of cardiovascular disease who were not at LDL-C goal, atorvastatin were usually initiated at medium-potency doses without escalation. These treatment patterns indicate the need for better patient and provider education as well as other system-wide modifications to improve medication adherence.
The authors have no financial relationships relevant to this article to disclose.
Potential Conflicts of Interest
The authors have no conflicts of interest relevant to this article to disclose.
This study was exempted from institutional review board approval.
- Greenland, P., et al., Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA, 2003. 290 (7): p. 891-7.
- Khot, U.N., et al., Prevalence of conventional risk factors in patients with coronary heart disease. JAMA, 2003. 290 (7): p. 898-904.
- Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 2002. 106 (25): p. 3143-421.
- Excellence, N.I.f.H.a.C., Statins for the prevention of cardiovascular events in patients at increased risk of developing cardiovascular disease or those with established cardiovascular disease.
- Agency, M.P.a., Prevention av aterosklerotisk hjartkarlsjukdom med lipidreglerande lakemedel. 2005.
- Welfare, N.B.o.H.a., Nationella riktlinjer for hjartsjukvard. Tabellbilaga till beslutsstodsdokument – tillstands- och atgardslistor for hjartsjukdomar. 2008.
- Baigent, C., 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): p. 1267-78.
- Mills, E.J., et al., Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM, 2011. 104 (2): p. 109-24.
- Statins for the prevention of cardiovascular events in patients at increased risk of developing cardiovascular disease or those with established cardiovascular disease. National Institute for Health and Clinical Excellence, 2006.
- Grundy, S.M., et al., Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol, 2004. 44 (3): p. 720-32.
- Gotto, A.M., Jr. and J.E. Moon, Recent clinical studies of the effects of lipid-modifying therapies. Am J Cardiol, 2012. 110 (1 Suppl): p. 15A-26A.
- Baigent, C., 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): p. 1670-81.
- Geleedst-De Vooght, M., et al., Statin prescribing in the elderly in the Netherlands: a pharmacy database time trend study. Drugs Aging, 2010. 27 (7): p. 589-96.
- Jackevicius, C.A., et al., Long-term trends in use of and expenditures for cardiovascular medications in Canada. CMAJ, 2009. 181 (1-2): p. E19-28.
- Ruokoniemi, P., et al., Shift of statin use towards the elderly in 1995-2005: a nation-wide register study in Finland. Br J Clin Pharmacol, 2008. 66 (3): p. 405-10.
- Deambrosis, P., et al., Evaluation of the prescription and utilization patterns of statins in an Italian local health unit during the period 1994-2003. Eur J Clin Pharmacol, 2007. 63 (2): p. 197-203.
- Walley, T., et al., Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997-2003. Br J Clin Pharmacol, 2005. 60 (5): p. 543-51.
- Mantel-Teeuwisse, A.K., et al., Time trends in lipid lowering drug use in The Netherlands. Has the backlog of candidates for treatment been eliminated? Br J Clin Pharmacol, 2002. 53 (4): p. 379-85.
- Larsen, J., et al., Changes in the utilisation of lipid-lowering drugs over a 6-year period (1993-1998) in a Danish population. Eur J Clin Pharmacol, 2001. 57 (4): p. 343-8.
- Li, M., et al., Utilization of lipid lowering medications among adults in the United States 1999-2006. Atherosclerosis, 2010. 208 (2): p. 456-60.
- Upmeier, E., et al., Statin use among older Finns stratified according to cardiovascular risk. Eur J Clin Pharmacol, 2013. 69 (2): p. 261-7.
- Rikala, M., et al., Channelling of statin use towards low-risk population and patients with diabetes. Basic Clin Pharmacol Toxicol, 2013. 113 (3): p. 173-8.
- Wallach Kildemoes, H., et al., Statin utilization according to indication and age: a Danish cohort study on changing prescribing and purchasing behaviour. Health Policy, 2012. 108 (2-3): p. 216-27.
- King Abdulaziz Medical City (KAMC). Ministry of National Guard Health Affairs (MNGHA) 2016; Available from: http://ngha.med.sa/English/MedicalCities/AlRiyadh/Pages/default.aspx.
- Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA, 2001. 285 (19): p. 2486-97.
- Stone, N.J., S. Bilek, and S. Rosenbaum, Recent National Cholesterol Education Program Adult Treatment Panel III update: adjustments and options. Am J Cardiol, 2005. 96 (4A): p. 53E-59E.
- Maggioni, A.P., et al., Epidemiologic study of use of resources in patients with unstable angina: the EARISA registry. On behalf on the EARISA Investigators (Epidemiologia dell’Assorbimento di Risorse nell’Ischemia, Scompenso e Angina). Am Heart J, 2000. 140 (2): p. 253-63.
- Aliprandi-Costa, B., et al., The design and rationale of the Australian Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE). Heart Lung Circ, 2013. 22 (7): p. 533-41.
- Fox, K.A., et al., Management of acute coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE). Eur Heart J, 2002. 23 (15): p. 1177-89.
- Zeymer, U., et al., Differences in the use of guideline-recommended therapies among 14 European countries in patients with acute coronary syndromes undergoing PCI. Eur J Prev Cardiol, 2013. 20 (2): p. 218-28.
- Ferrajolo, C., et al., Pattern of statin use in southern italian primary care: can prescription databases be used for monitoring long-term adherence to the treatment? PLoS One, 2014. 9 (7): p. e102146.
- Jaiswal, M., A. Schinske, and R. Pop-Busui, Lipids and lipid management in diabetes. Best Pract Res Clin Endocrinol Metab, 2014. 28 (3): p. 325-38.
- Lepor, N.E. and R.E. Vogel, Summary of the third report of the National Cholesterol Education Program Adult Treatment Panel III. Rev Cardiovasc Med, 2001. 2 (3): p. 160-5.
- Nag, S.S., et al., LDL-C goal attainment among patients newly diagnosed with coronary heart disease or diabetes in a commercial HMO. J Manag Care Pharm, 2007. 13 (8): p. 652-63.
- Simpson, R.J., Jr., et al., Treatment pattern changes in high-risk patients newly initiated on statin monotherapy in a managed care setting. J Clin Lipidol, 2013. 7 (5): p. 399-407.
- Marrett, E., et al., Limitations of real-world treatment with atorvastatin monotherapy for lowering LDL-C in high-risk cardiovascular patients in the US. Vasc Health Risk Manag, 2014. 10: p. 237-46.
- Kauffman, A.B., et al., Attainment of low-density lipoprotein cholesterol goals in coronary artery disease. J Clin Lipidol, 2010. 4 (3): p. 173-80.
- Waters, D.D., et al., Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation, 2009. 120 (1): p. 28-34.
- Table 1: Patients’ demographic and other characteristics.
- Table 2: Description of lipid profiles at initiation of Atorvastatin.
- Table 3: Relationship between LDL-C Level and Atorvastatin Starting Dose.
- Table 4: Description of documented patients’ instructions on lifestyle and diet modifications.
- Figure 1: Relationship between LDL-C Level and Atorvastatin Starting Dose.