Table of Contents
ISRN Pharmacology
Volume 2013 (2013), Article ID 146579, 7 pages
http://dx.doi.org/10.1155/2013/146579
Research Article

Comparison of Efficacy and Safety of Rosuvastatin, Atorvastatin and Pravastatin among Dyslipidemic Diabetic Patients

1Departments of Pharmacy and Clinical Pharmacy, Hamad General Hospital, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
2Departments of Medicine and Endocrinology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
3Department of Medical Statistics and Epidemiology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
4Departments of Public Health and Medical Education, Weill Cornell Medical College in Qatar, P.O. Box 3050, Doha, Qatar
5Department of Evidence for Population Health Unit, School of Epidemiology and Health Sciences, The University of Manchester, Manchester, UK
6Pediatric Intensive Care Unit, Department of Pediatrics, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

Received 6 December 2012; Accepted 3 January 2013

Academic Editors: T. Kumai and T. B. Vree

Copyright © 2013 Lolwa Barakat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives. To investigate the efficacy and the safety of the three most commonly prescribed statins (rosuvastatin, atorvastatin, and pravastatin) for managing dyslipidemia among diabetic patients in Qatar. Subjects and Methods. This retrospective observational population-based study included 350 consecutive diabetes patients who were diagnosed with dyslipidemia and prescribed any of the indicated statins between September 2005 and September 2009. Data was collected by review of the Pharmacy Database, the Electronic Medical Records Database (EMR viewer), and the Patient's Medical Records. Comparisons of lipid profile measurements at baseline and at first- and second-year intervals were taken. Results. Rosuvastatin (10 mg) was the most effective at reducing LDL-C (29.03%). Atorvastatin reduced LDL-C the most at a dose of 40 mg (22.8%), and pravastatin reduced LDL-C the most at a dose of 20 mg (20.3%). All three statins were safe in relation to muscular and hepatic functions. In relation to renal function, atorvastatin was the safest statin as it resulted in the least number of patients at the end of 2 years of treatment with the new onset of microalbuminuria (10.9%) followed by rosuvastatin (14.3%) and then pravastatin (26.6%). Conclusion. In the Qatari context, the most effective statin at reducing LDL-C was rosuvastatin 10 mg. Atorvastatin was the safest statin in relation to renal function. Future large-scale prospective studies are needed to confirm these results.

1. Introduction

Diabetes is now commonly recognized as a “coronary heart disease risk equivalent” [14]. This is mainly attributed to the high rates of dyslipidemia among diabetic patients which is believed to be one of the major factors accounting for the high percentage of deaths among diabetics due to cardiovascular disease (CVD) [5].

The differences in the lipid profile between diabetics (especially type 2 diabetics) and nondiabetics account for the increased CVD risk [6]. Essentially, T2DM lipid profiles consist of elevations in triglyceride (TG) levels (>2 mmol/L) and reductions in high-density lipoprotein cholesterol (HDL-C). While low-density lipoproteins cholesterol (LDL-C) concentration levels are normal, the particles are denser and smaller in size, which is believed to enhance their atherogenic potential [7].

Numerous epidemiological studies and randomized controlled trials have documented the association between elevated LDL-C levels with increased CVD risk in both diabetic and nondiabetic populations [8, 9]. Thus reducing LDL-C levels is the primary goal of therapy for diabetic dyslipidemia [5, 10]. On the other hand, raising HDL-C and reducing triglycerides have been associated with moderate reductions in CVD risk and are thus regarded as of secondary importance [11].

Statins are considered the first pharmacological line of treatment of dyslipidemia in diabetic patients [12]. Lowering of LDL-C levels is thought to be the main beneficial effect of statin treatment; although, effects on HDL-C and other lipoproteins also play a role [5]. There are currently seven approved statins which are commonly prescribed, and each has a different benefit-risk profile [13].

To date, numerous randomized trials among various ethnicities have documented that rosuvastatin is the most effective statin at reducing LDL-C and triglycerides (TG) and at raising HDL-C levels [14, 15]. Atorvastatin, on the other hand, was previously, before the approval of rosuvastatin, documented to be the most potent statin at reducing LDL-C levels [16]. Alternatively, pravastatin which is available at the higher doses of 20 mg and 40 mg is found to be slightly less effective; the main reason for its prescription in patients is put down to its hydrophilic properties which make it more tolerable to patients with greater risk factors in addition to CVD [17].

Statins, like all other pharmacological treatments, inevitably have adverse side effects. The muscular system, hepatic function, and renal function have been documented to be affected by statin treatment [18, 19]. In general, large-scale randomized clinical trials have consistently demonstrated that statin therapy causes only a slight increased risk of side effects compared with placebo [20, 21]. For instance, postmarketing data report an overall adverse event frequency of less than 0.5% and a myotoxicity event rate of less than 0.1% [22].

In Qatar, there are currently no guidelines available for treating diabetic patients with dyslipidemia, and no previous study has documented the efficacy and safety of the various statins prescribed to diabetic patients. Thus the current study aims to build on this growing awareness of atherosclerosis-specific care of diabetes patients, by examining efficacy and safety of the three most commonly prescribed statins in the State of Qatar.

2. Methods

This retrospective observational population-based study was conducted in Hamad General Hospital, Hamad Medical Corporation which is the main tertiary hospital in Qatar serving, over 90% of the population of Qatar [23].

2.1. Study Patients

The study population was drawn from consecutive diabetic patients who presented to Hamad General Hospital with dyslipidemia and were prescribed the indicated statins and underwent fasting blood test of lipid profile before statin treatment initiation between September 2005 and September 2009. The diagnosis and when to treat dyslipidemia in diabetics in Hamad General Hospital are established on the basis of WHO expert group [24] criteria; the WHO recommends screening for lipid disorders at least annually in diabetic patients and more often if needed to achieve goals. On the other hand, adults with low-risk lipid values (LDL-C < 100 mg/dL [2.6 mmol/L], HDL-C > 50 mg/dL [1.3 mmol/L], and triglycerides < 150 mg/dL [1.7 mmol/L]) may be screened every two years.

The inclusion criteria included diabetic patients (fasting blood glucose ≥ 126 mg/dL [7.0 mmol/L]) who were prescribed any of the indicated statins (rosuvastatin, atorvastatin, pravastatin) during 2005–2009 (2 years within this period) to ensure at least 2 years of using the statin, aged ≥ 18 years, and had a total cholesterol level of ≥4 mmol/L, LDL-C ≥2.5 mmol/L, HDL-C ≤ 1 mmol/L in men and ≤1.2 mmol/L in women, and fasting triglycerides ≥ 1.7 mmol/L, obtained within 1 week before the first use of statins which will be then compared at first- and second-year intervals.

This study excluded pregnant women; patients with genetic disorders; patients on other concurrent lipid lowering agents such as bile acid sequestrants (cholestyramine, colesevelam), niacin, ezetimibe, fenofibrate and/or omega 3; patients with previous history of angina, severe vascular disease, or other life threatening disease; patients with nephropathy and/or hypothyroidism, active liver disease, bile duct problems, or ALT > 3 ULN; patients with creatine kinase levels > 10 ULN; patients taking concurrent corticosteroids, ciclosporin, and/or hormone replacement therapy; patients who are physically inactive; patients with a history of drug or alcohol abuse.

IRB ethical approval, for this study, was obtained from Medical Research Committee of Hamad Medical Corporation prior to commencement of data collection.

2.2. Data Collection

Patients were identified as statin users (rosuvastatin, atorvastatin, pravastatin) during the study period (September 2005–September 2009) by using the Pharmacy Database. Data collection sheets were designed by the researcher for each patient. Fifty patients were included in the study for each statin dose, and these had to have been on the same dose for at least 2 years between the periods indicated previously. The data for these patients were obtained from 2 sources which are the electronic medical database called (EMR viewer) and the patients’ files from the Medical Records Department of Hamad Medical Corporation (HMC). The prescribed doses in HMC for diabetic patients with dyslipidemia are as follows:(i)rosuvastatin 10 mg and 20 mg, (ii)pravastatin 20 mg and 40 mg, (iii)atorvastatin 10 mg, 20 mg, and 40 mg.

Patients had been checked 3 times to exclude duplications which finally resulted in a total sample of 350 patients.

2.3. Data Collection Sheet

The researcher developed a structured data collection sheet for this study. The measures consisted of questions relating to sociodemographic data, medical history, and comorbid factors, lifestyle habits, lab investigations, and patient’s antihypertensive medications (ARBs and/or ACE inhibitors). The designed data collection sheet was tested among 25 patients as a pilot study. Thereafter, any discrepancies found between the data collection sheet and the data available in the Medical Record were resolved.

The first part included the type of statin prescribed for the patient for at least 2 years continuously and dose of statin. The second part included information about sociodemographic characteristics including age, sex, nationality, height, weight, and BMI. Lifestyle habits like smoking and alcohol intake were included in the second section. The third section collected information about type of DM, its duration, and presence of hypertension. The fourth section included items about laboratory investigations such as fasting blood glucose, glycated hemoglobin (HbA1C), total cholesterol, HDL and LDL cholesterol levels, triglycerides, creatine kinase level, serum creatinine, bilirubin, LFTs, GGT, and serum albumin and adverse events like microalbuminuria and macroalbuminuria. Finally the fifth section included the initiation of antihypertensive medications (ARBs and/or ACE inhibitors).

2.4. Statistical Analysis

Data were analyzed using SPSS version 20. Student’s -test was used to ascertain the significance of differences between mean values of two continuous variables and confirmed by nonparametric Mann-Whitney test. In addition, paired t-test was used to determine the difference between baseline and 2 years after regarding biochemistry parameters, and this is confirmed by the Wilcoxon test which is a nonparametric test that compares two paired groups. Chi-square and Fisher exact tests were performed to test for differences in proportions of categorical variables between two or more groups. The level was considered as the cutoff value or significance.

3. Results

Table 1 presents the sociodemographic characteristics of the study population. The majority of patients were Qatari, had a BMI > 30 kg/m2, and had comorbid hypertension.

tab1
Table 1: Socio-demographic characteristics of study population ( ).

Table 2 and Figures 1 and 2 show the comparison of the efficacy of each statin at each dose (10 mg, 20 mg, and 40 mg). Rosuvastatin (10 mg and 20 mg) was the most effective at reducing LDL-C (29.03% and 29.3%, resp.). Atorvastatin reduced LDL-C the most at a dose of 40 mg (22.8%), and pravastatin reduced LDL-C the most at a dose of 20 mg (20.3%). Moreover, rosuvastatin (10 mg) reduced triglycerides the most (−25.1%, ). This was the case, even in comparison to higher doses of rosuvastatin (20 mg) and to higher doses of atorvastatin (20 mg and 40 mg) and pravastatin (20 mg and 40 mg). Finally, all of the statins appear to have reduced rather than raised HDL-C levels.

tab2
Table 2: Comparison of the efficacy of statins for all doses (10 mg, 20 mg, and 40 mg).
146579.fig.001
Figure 1: (%) Change in LDL-C from baseline.
146579.fig.002
Figure 2: Rosuvastatin versus other statins, change in triglycerides.

Figure 3 presents the percentage of patients with the new onset of microalbuminuria after taking statins. Atorvastatin was the safest statin as it resulted in the least number of patients at the end of 2 years of treatment with the new onset of microalbuminuria (10.9%) followed by rosuvastatin (14.3%) and then pravastatin (26.6%).

146579.fig.003
Figure 3: Number of patients with no microalbuminuria at baseline but developed it after 2 years.

Table 3 presents an overview of the safety profile of each of the statins at their various doses among patients. Statins appear to be safe in relation to hepatic and muscular functions as no patients presented with ALT > 3 ULN or CK > 10 ULN. A slightly adverse effect of statins on renal function was observed due to the new onset of microalbuminuria among some of the patients; nonetheless no case of microalbuminuria progressed to the more dangerous macroalbuminuria.

tab3
Table 3: Safety comparison on hepatic, renal, and muscular functions: adverse events after 2 years of statin use.

4. Discussion

In the present study, rosuvastatin (10 mg and 20 mg) was found to be the most effective statin at reducing LDL-C when compared with atorvastatin (10 mg, 20 mg, and 40 mg) and pravastatin (20 mg and 40 mg). In other words, rosuvastatin at its lowest dose in this study (10 mg) was more effective at reducing LDL-C levels than atorvastatin and pravastatin at their highest doses (40 mg). Indeed, it should be noted that rosuvastatin, which is the latest statin to receive approved labeling by the Food and Drug Administration, has been consistently found to be the most effective at reducing LDL-C levels in the most recent studies comparing its efficacy to other statins [25]. Our results are consistent with STELLAR trial which is one of the major open-label, randomized, and multicenter trials to compare rosuvastatin (10, 20, 40, or 80 mg) with atorvastatin (10, 20, 40, or 80 mg), pravastatin (10, 20, or 40 mg), and simvastatin (10, 20, 40, or 80 mg) across dose ranges for reduction of LDL-C [15]. The results of the STELLAR trial revealed that rosuvastatin was consistently, across all doses, the most effective at reducing LDL-C levels in comparison to all of the other statins.

The lowering of triglycerides is another important goal in reducing CVD risk among diabetic patients [5]. In the current study, the greatest reduction in triglycerides was (−25.1%, ) and was achieved by patients taking rosuvastatin (10 mg). This was the case, even in comparison to higher doses of rosuvastatin (20 mg) and to higher doses of atorvastatin (20 mg and 40 mg) and pravastatin (20 mg and 40 mg). However, it is important to note that atorvastatin (10 mg and 40 mg) both achieved the second highest reduction in triglycerides (−21.05%, , and −21.56%,   ), respectively. These findings are similar to the majority of studies in the literature, which have shown a slightly higher reduction in triglycerides in patients taking rosuvastatin in comparison to atorvastatin [26]. It thus appears that, in relation to this factor (triglycerides), that both rosuvastatin and atorvastatin are effective at reducing it.

Raising HDL-C levels is another major factor known to reduce CVD risk [11, 27]. In the current study, all of the statins appear to have reduced rather than raised HDL-C levels. Rosuvastatin (20 mg) had the least reduction of (−4.0%) and would thus be regarded as the most effective; however, none of the values for the statins were significant.

In this instance, the findings in the current study are contrary to the studies in the literature. For example, the STELLAR trial [15] found rosuvastatin (40 mg) to be the most effective on increasing HDL-C. In fact it is noted that across dose ranges, the HDL cholesterol increasing effect of rosuvastatin was consistent across the dose range and was significantly higher ( ) compared with those of simvastatin and pravastatin [15]. As for the PULSAR [26] study which investigated starting doses of rosuvastatin and atorvastatin, they found that the increase in HDL-C was significantly greater statistically with rosuvastatin (10 mg) than with atorvastatin (20 mg).

A number of factors could be at play which could explain the discrepancy between the current study’s results and those in the international literature. It is evident from Table 1 which has the patient characteristics that many of the patients had more than two risk factors for CVD. For instance, the patients were diabetic, and most of them were over 55 years old and had hypertension. In addition, over two-thirds of the patients were obese and Qatari. In other diabetic research studies conducted in Qatar, it was found that having Qatari ethnicity was correlated with poor lifestyle habits such as sedentary lifestyle and poor eating choices [2, 3]. In other words, the subjects had so many other factors which caused their HDL-C levels to be so low that the statins were only able to have a minimal effect.

One of the most common complaints related to statin use is related to the effect of statins on muscular function. Muscle symptoms range from myalgia, which includes muscle pain without creatine kinase (CK) elevations, to myositis which is muscle symptoms with CK elevations [18]. In general, elevations of CK of more than ten times the upper limit of normal are regarded as significant elevations justifying the discontinuation of statin treatment [28]. In the current study, there were no cases of elevations of CK level > 10 ULN. In other words, all statins, irrespective of dose, were regarded as safe in terms of myositis.

Hepatic function is also known to be affected by statin use [18]. This is mainly measured by asymptomatic elevations of the liver enzymes ALT and AST, otherwise known as transaminitis [29]. In the current study, no patients had elevated ALT > 3 upper limit of normal. Thus there were no adverse events related to hepatic function reported with the use of any of the statins in the study. This is not surprising, as clinical trials have reported a 0.5–3.0% occurrence of elevations in aminotransferases among patients receiving statins and very rare episodes of severe liver injury. In general, the incidence of hepatic failure in patients taking statins appears to be in different from that in the general population [29].

In the current study, the three statins (atorvastatin 10, 20, and 40 mg; rosuvastatin 10 and 20 mg; and pravastatin 20 and 40 mg) with different doses did not significantly affect the serum creatinine and GFR after 2 years. In addition, the three statins appeared to be relatively safe for patients with microalbuminuria at baseline, as the number of those whose microalbuminuria increased was very minimal. In fact, pravastatin (40 mg) appeared to reduce the number of patients with baseline microalbuminuria. On the other hand, in patients without baseline microalbuminuria, there appeared to be relatively significant onset of microalbuminuria in patients taking pravastatin (26.6%) and to a lesser degree rosuvastatin (14.3%) and atorvastatin (10.9%). The literature relating to the effect of statins on microalbuminuria is somewhat controversial. While some statin trials have reported a reduction in proteinuria [30] or no effect [31], some of the literature supports the findings in the current study that statins do have negative effects relating to the onset of proteinuria [19]. The main reason stated for atorvastatins’ safety in relation to renal function is its somewhat unique method of metabolism; in that it has the least degree of renal excretion (2%), followed by fluvastatin (5%), rosuvastatin (10%), lovastatin (10%), simvastatin (13%), and pravastatin (20%) [32].

5. Conclusion

The results obtained in the current study have shown that rosuvastatin is the most effective statin at reducing LDL-C, triglycerides, and total cholesterol, at the lowest dose (10 mg). Moreover, it reduced HDL-C the least in comparison to the other statins. Thus in the Qatari diabetic dyslipidemic population it appears to be the most effective statin. In addition, this study provides a good base for future large-scale prospective studies to be conducted on the topic.

Acknowledgments

This paper is based on the M.S. degree thesis in clinical pharmacy submitted by L. Barakat to Queen’s University Belfast in 2012. The authors would like to acknowledge the assistance provided by Dr. Christopher Scott to Ms. L. Barakat, as a supervisor of the M.S. degree thesis. This work was generously supported and funded by the Hamad Medical Corporation Grant no. HMC RP# 11212/11. The authors would like to thank the Hamad Medical Corporation for their support and ethical approval.

References

  1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), “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, vol. 106, no. 25, article 3143, 2002. View at Google Scholar
  2. A. Bener, M. Zirie, I. M. Janahi, A. O. A. A. Al-Hamaq, M. Musallam, and N. J. Wareham, “Prevalence of diagnosed and undiagnosed diabetes mellitus and its risk factors in a population-based study of Qatar,” Diabetes Research and Clinical Practice, vol. 84, no. 1, pp. 99–106, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Bener, M. Zirie, M. Musallam, Y. S. Khader, and A. O. A. A. Al-Hamaq, “Prevalence of metabolic syndrome according to adult treatment panel III and international diabetes federation criteria: a population-based study,” Metabolic Syndrome and Related Disorders, vol. 7, no. 3, pp. 221–230, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Bener, E. Dafeeah, S. Ghuloum, and A. O. A. A. Al-Hamaq, “Association between psychological distress and gastrointestinal symptoms in type 2 diabetes mellitus,” World Journal of Diabetes, vol. 3, no. 6, pp. 123–129, 2012. View at Publisher · View at Google Scholar
  5. J. D. Brunzell, M. Davidson, C. D. Furberg et al., “Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American diabetes association and the american college of cardiology foundation,” Diabetes Care, vol. 31, no. 4, pp. 811–822, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. T. O'Brien, T. T. Nguyen, and B. R. Zimmerman, “Hyperlipidemia and diabetes mellitus,” Mayo Clinic Proceedings, vol. 73, no. 10, pp. 969–976, 1998. View at Google Scholar · View at Scopus
  7. R. M. Krauss, “Lipids and lipoproteins in patients with type 2 diabetes,” Diabetes Care, vol. 27, no. 6, pp. 1496–1504, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. H. M. Colhoun, D. J. Betteridge, P. N. Durrington et al., “Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the collaborative atorvastatin diabetes study (CARDS): multicentre randomised placebo-controlled trial,” The Lancet, vol. 364, no. 9435, pp. 685–696, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Shepherd, P. Barter, R. Carmena et al., “Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the treating To new targets (TNT) study,” Diabetes Care, vol. 29, no. 6, pp. 1220–1226, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. American Diabetes Association, “Standards of medical care in diabetes,” Diabetes Care, vol. 32, supplement 1, pp. S13–S61, 2009. View at Google Scholar
  11. S. J. Nicholls, E. M. Tuzcu, I. Sipahi et al., “Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis,” The Journal of the American Medical Association, vol. 297, no. 5, pp. 499–508, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. R. R. Henry, “Preventing cardiovascular complications of type 2 diabetes: focus on lipid management,” Clinical Diabetes, vol. 19, no. 3, pp. 113–120, 2001. View at Publisher · View at Google Scholar
  13. D. J. Maron, S. Fazio, and M. F. Linton, “Current perspectives on statins,” Circulation, vol. 101, no. 2, pp. 207–213, 2000. View at Google Scholar · View at Scopus
  14. R. S. Rosenson, “Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia,” Expert Review of Cardiovascular Therapy, vol. 1, no. 4, pp. 495–505, 2003. View at Google Scholar · View at Scopus
  15. P. H. Jones, M. H. Davidson, E. A. Stein et al., “Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* trial),” American Journal of Cardiology, vol. 92, no. 2, pp. 152–160, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. A. S. Brown, R. G. Bakker-Arkema, L. Yellen et al., “Treating patients with documented atherosclerosis to national cholesterol education program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin,” Journal of the American College of Cardiology, vol. 32, no. 3, pp. 665–672, 1998. View at Publisher · View at Google Scholar · View at Scopus
  17. B. A. Hamelin and J. Turgeon, “Hydrophilicity/Lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors,” Trends in Pharmacological Sciences, vol. 19, no. 1, pp. 26–37, 1998. View at Publisher · View at Google Scholar · View at Scopus
  18. A. R. Vasudevan, Y. S. Hamirani, and P. H. Jones, “Safety of statins: effects on muscle and the liver,” Cleveland Clinic Journal of Medicine, vol. 72, no. 11, pp. 990–1001, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. A. A. Alsheikh-Ali and R. H. Karas, “The relationship of statins to rhabdomyolysis, malignancy, and hepatic toxicity: evidence from clinical trials,” Current Atherosclerosis Reports, vol. 11, no. 2, pp. 100–104, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Kashani, C. O. Phillips, J. M. Foody et al., “Risks associated with statin therapy: a systematic overview of randomized clinical trials,” Circulation, vol. 114, no. 25, pp. 2788–2797, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Armitage, “The safety of statins in clinical practice,” The Lancet, vol. 370, no. 9601, pp. 1781–1790, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Evans and A. Rees, “Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same?” Drug Safety, vol. 25, no. 9, pp. 649–663, 2002. View at Google Scholar · View at Scopus
  23. Annual Health Report, Vital Health Statistics, Hamad Medical Corporation, Doha, Qatar, 2010.
  24. World Health Organization, “Definition, diagnosis and classification of diabetes mellitus and its complications,” Report of a WHO Consultation WHOINCDINCS/99. 2, World Health Organization, Geneva, Switzerland, 1999. View at Google Scholar
  25. J. M. Mckenney, “Efficacy and safety of rosuvastatin in treatment of dyslipidemia,” American Journal of Health-System Pharmacy, vol. 62, no. 10, pp. 1033–1047, 2005. View at Google Scholar · View at Scopus
  26. M. B. Clearfield, J. Amerena, J. P. Bassand et al., “Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia—prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR),” Trials, vol. 7, article 35, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. B. G. Brown, X. Q. Zhao, and M. C. Cheung, “Should both HDL-C and LDL-C be targets for lipid therapy? A review of current evidence,” Journal of Clinical Lipidology, vol. 1, no. 1, pp. 88–94, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Tiwari, V. Bansal, A. Chugh, and K. Mookhtiar, “Statins and myotoxicity: a therapeutic limitation,” Expert Opinion on Drug Safety, vol. 5, no. 5, pp. 651–666, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. E. Björnsson, E. I. Jacobsen, and E. Kalaitzakis, “Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing,” Journal of Hepatology, vol. 56, no. 2, pp. 374–380, 2012. View at Publisher · View at Google Scholar
  30. K. Douglas, P. G. O'Malley, and J. L. Jackson, “Meta-analysis: the effect of statins on albuminuria,” Annals of Internal Medicine, vol. 145, no. 2, pp. 117–124, 2006. View at Google Scholar · View at Scopus
  31. J. Atthobari, A. H. Brantsma, R. T. Gansevoort et al., “The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study,” Nephrology Dialysis Transplantation, vol. 21, no. 11, pp. 3106–3114, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. J. M. McKenney, “Defining the pharmacological profile of rosuvastatin: a look at statin therapy for dyslipidemia,” France foundation web site poster: advances in managing hyperlipidemia online continuing medical education activity, 2005, http://www.francefoundation.com/cme/posttest/pages/amh_posters.pdf.