16-original.pmd

Shimal Khan, et al.
ORIGINAL ARTICLE
EFFICACY AND SAFETY OF ROSUVASTATIN
COMPARED TO SIMVASTSTIN IN CORONARY
ARTERY DISEASE
Shimal Khan, Amjad Abrar, Ahmad Rafique, Abdul Rehman Abid, Tehmina Jan
Department of Pharmacology, , Gomal Medical College D ABSTRACT
Background: Coronary artery disease is the leading cause of morbidity and mortality worldwide. Hyperlipi-
demia is a major risk factor for it. This trial was conducted to compare the efficacy and safety of rosuvastatin
and simvastatin in patients with coronary artery disease.
Material & Methods: This study was conducted at Pharamacology Department, Gomal Medical College,
D.I.Khan from May 1, 2008 to December 31, 2008. Patients with history of coronary artery disease were
randomized to receive Rosuvastatin 5mg or Simvastatin 20mg for six weeks. Primary end point was number
of patients achieving National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) target
LDL-C<100mg/dl, while secondary end points were reduction of LDL-Cholesterol, Total Cholesterol and
increase in HDL-Cholesterol and safety profile of the two drugs.
Results: Eighty patients were randomized into two groups. Rosuvastatin Group consisted of 23(57.5%)
males and 17(42.5%) females while Simvastatin Group 22(55%) males and 18(45%) females. Mean age was
55.35±9.7 and 55.7±8.6 years respectively. Primary end point was achieved in significantly higher number
of patients in Rosuvastatin Group 30(75%) as compared to Simvastatin 17(42.5%), p=0.003. Significantly
greater reduction in LDL-C from baseline occurred in Rosuvastatin group 78.2±6.14 mg/dl (44.3%) as
compared to 66.8±9.9 mg/dl(37.7%) in Simvastatin, p<0.001. Total cholesterol was significantly reduced in
Rosuvastatin group 98.5±8.8mg/dl (38.6%) as compared to 78.4±7.8mg/dl (30.4%) in Simvastatin, p<0.001.
Increase in HDL-C was significantly greater in Rosuvastatin 4.4±0.87 mg/dl(11.5%) as compared to
2.45±0.55mg/dl(6.5%) in Simvastatin, p=0.009. Both treatments were well tolerated with no serious ad-
verse effects.
Conclusion: Rosuvastatin is more efficacious in modifying lipid profile and has comparable safety and
adverse event profile to Simvastatin.
Key words: Rosuvastatin, Coronary Artery Disease, Cholesterol, LDL Cholesterol, HDL Cholesterol.
INTRODUCTION
which is rate limiting enzyme of cholesterol syn-thesis.7 Results of various trails have shown that Coronary artery disease (CAD) is the leading Statins are the most efficacious drugs in primary cause of morbidity and mortality world wide.1 It is and secondary prevention of CAD by reducing LDL- also the leading cause of death of adult popula- C levels but residual morbidity and mortality is tion of Pakistan.2 Hyperlipidemia is a major risk factor for the development of CAD.3 The risk ofCAD increases by 2-4 fold by increase in level of Despite the guidelines and availability of the LDL-C (Low Density Lipoprotein Cholesterol).4 The lipid lowering therapy many patients fail to reach direct relationship between CAD and serum lipids the desired goals, depriving the remaining from has led to the development of strategies aimed in the beneficial effects of statin therapy.9 This treat- reducing LDL-C resulting in significant reduction ment gap has considerable clinical and economi- in morbidity and mortality.5 4S trail showed 42% cal implications in terms of preventing cardiovas- reduction in mortality by reducing LDL-C by 35%.6 cular events and increased costs to health careplans.10 Statins are the diverse class of drugs that lower cholesterol levels in patients with and with- More recent studies have shown that cardio- out at risk of CAD by inhibiting the enzyme 3-hy- vascular end points are further reduced with even droxy-3-methylglutaryl-CoA (HMG-CoA reductase), more lower level of LDL-C suggesting for the de- Gomal Journal of Medical Sciences January-June 2010, Vol. 8, No. 1
Rosuvastatin compared to Simvastatin
velopment of more effective form of lipid lowering of the study was achievement of NCEP ATP III tar- therapy.11 Clinical trails have shown that get LDL-C <100mg/dl in both the groups. Sec- Rosuvastatin provides the greatest LDL-C reduc- ondary end points were the change of LDL-C, HDL- tion as compared to other Statins.12,13 But no such C and TC from baseline between the two groups data is available in our part of country so we con- and the safety of two treatment drugs evaluated ducted this study to compare the efficacy and through clinical assessment of adverse events and safety of Rosuvastatin with Simvastatin in achiev- elevation of ALT >3 times upper limit normal (ULN) ing National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III)11 target LDL-C level All data was analyzed using SPSS 11 for win- dows. Categorical variables were expressed as fre-quencies and percentages while continuous vari- MATERIAL AND METHODS
ables were expressed as Mean ± SD. Compara-tive analysis between the two groups were done This study was conducted at Pharamacology using Chi-Square (x2) and student ‘t’ test where ap- Department, Gomal Medical College, Dera Ismail propriate. A p value of <0.05 was taken as signifi- Khan from 1st May 2008 to 31st December 2008. A total of 80 patients between 18-70 years of agewith history of CAD who had their LDL-C >160 mg/dl were randomized to receive Rosuvastatin5mg and Simvastatin 20 mg for six weeks. Pa- A total of 80 patients were randomized to tients with history of hypersensitivity to Statins, receive Rosuvastatin 5mg and Simvastatin 20mg pregnancy, breast feeding, use of oral contracep- for six weeks. There were 40 patients in each group.
tive pills (OCP’s), impaired renal and liver func- Mean age of patients was 55.35 ± 9.7years in tions, uncontrolled diabetes, uncontrolled hyper- Rosuvastatin group and 55.7 ± 8.6years in tension and unstable angina were excluded from Simvastatin group. There were 23 (57.5%) males the study. Demographic variables of the study and 17(42.5%) females in Rosuvastatin group, while population were recorded on preformed proforma.
Simvastatin group consisted of 22(55%) males and All the patients were advised to continue lipid low- ering diet during the course of study. LDL-C, Hypertension was present in 30(75%) patients TC(Total Cholestrol), HDL-C (High Density Lipo- in Rosuvastatin group patients and 29(72.5%) pa- protein Cholesterol), Creatine kinase (CK), Alanine tients in Simvastatin group. There were 17(42.4%) aminotransferase (ALT) ,Urea, Creatinine were car- patients suffering from Angina Pectoris in ried out in all the patients at week 0 and then at Rosuvastatin group and 20(50%) patients in the end of study at week 6. The primary endpoint Table 1: Demographic variables of the patients.
Variable
Rosuvastatin Group
Simvastatin Group
Age (years) Mean
Diabetes
Hypertension
Angina pectoris
Abbreviations:
Myocardial Infarction = MI; Coronary Artery Bypass Grafting = CABG;Percutaneous Coronary Intervention = PCI.
Gomal Journal of Medical Sciences January-June 2010, Vol. 8, No. 1
Shimal Khan, et al.
Table 2: Change from baseline in LDL-C and Total Cholesterol after six weeks of treatment.
Rosuvastatin Group
Simvastatin Group
Mean change
Mean change
from base
from base
Base line
Base line
176.35±11.2 98.2±8.95 78.18±6.14 177.2±11.2 110.4±15.7 66.8±9.9 < 0.0001 Abbreviations:
Low Density Lipoprotein Cholesterol = LDL-C, Total Cholesterol = TC,High Density Lipoprotein Cholesterol = HDL-C.
* For percentage change from baseline with Rosuvastatin Group versus Simvastatin Group at 6 weeks
Table 3: Number of patients with Side effects.
Variable
Rosuvastatin
Simvastatin
Group n=40
Group n=40
Abdominal pain
Abbreviations: Alanine aminotransferase = ALT, Creatine kinase = CK
Rosuvastatin group had significantly greater similar in two groups. Myalgia was the most fre- quent reported adverse event in both the groups.
176.35±11.2 mg/dl to 98.2±8.95 mg/dl) as com- There was only 1(2.5%) patient from both the groups with ALT within 1-2 times ULN; while CK 177.2±11.2 mg/dl to 110.4 ±15.7 mg/dl), was raised to 1- 2 times ULN in 2(5%) patients in Rosuvastatin group and 1(2.5%) patient inSimvastatin group, Table 3, with no patients hav- ing ALT >3 times ULN or CK > 10 times ULN. No achieved NCEP ATP III target goal of LDL-C after serious side effects were reported in both the six weeks of therapy in Rosuvastatin group 30 (75%) as compared to Simvastatin group17(42.5%) ,P = 0.003, Figure 1.
DISCUSSION
Total Cholesterol was reduced significantly Elevated LDL-C is important contributing fac- in Rosuvastatin group, 38.6% (from 254.8 ±20.6 tor for development of atherosclerosis and is rec- mg/dl to 156.4 ±14.6 mg/dl) as compared to ognized as the major risk factor for CAD, as a re- Simvastatin group, 30.4% (from 258.5±19.4 mg/ sult LDL-C is the key therapeutic target for the pre- dl to 180±17.4 mg/dl), p<0.0001, Table 2.
vention of CAD, with Statin as the first line treat- Increase in HDL-C was significantly greater in Rosuvastatin group, 11.5% (from 38.25±4.6 mg/dl to 42.65±4.65.19mg/dl) as compared to In this randomized trial comparing the effi- Simvastatin group, 6.5%(from 37.45±4.4 mg/dl to cacy and safety of Rosuvastatin with Simvastatin showed that Rosuvastatin has greater efficacy inachieving NCEP ATP III LDL-C level as compared Both treatments were well tolerated and the to Simvastatin over six weeks of treatment in pa- overall frequency and type of adverse events were Gomal Journal of Medical Sciences January-June 2010, Vol. 8, No. 1
Rosuvastatin compared to Simvastatin
Fig. 1: Percentage of patients achieving ATP III LDL Cholesterol after six weeks of treatment.
In our study, at six weeks, mean LDL-C de- in high risk patients unable to achieve lipid goals creased by 44.3% in Rosuvastatin group as com- pared to 37.7% in Simvastatin group. Brown etal12 reported 39.1% decrease in LDL-C in Rosuvastatin group as compared to 34.6% in improvement in other components of lipid profile Simvastatin group. Meta-analysis by Law and col- may be beneficial in reducing risk in patients with leagues14 showed 38% reduction in LDL-C in In our study, Rosuvastatin showed a statisti- Simvastatin group which is similar to our results.
cally significant decrease in TC, 38.6% as com- DISCOVERY-Beta15 study reported a decrease of pared to 30.4% in Simvastatin. This decrease in 38.79% in LDL-C in Rosuvastatin group as com- TC is similar to reported by other studies. In MER- pared to 32.03% in Simvastatin group.
CURY II trial16, 37% decrease in TC is reportedwith Rosuvastatin as compared to 24.1% with Achievement of LDL-C targets in high risk Simvastatin. Edwards and Moore 18 in their Meta- patients have been a challenging objective in clini- cal practice.15 The significantly greater decrease in LDL-C with Rosuvastatin as compared to Simvastatin group. Brown et al12 reported 28% Simvastatin in our study enabled more patients in decrease in TC in Rosuvastatin as compared to the Rosuvastatin group to achieve NCEP ATP III target LDL-C, 30 (75%) in Rosuvastatin group vs17(42.5%) in Simvastatin group, p=0.003.Our re- After 6 weeks of treatment HDL-C increased sults are similar with other trials. In MERCURY II16 by 11.5% in Rosuvastatin group as compared to trial target LDL-C was achieved in 82% patients the Simvastatin group 6.5%.This increase is simi- with Rosuvastatin as compared to 33% with lar to reported by other studies. Edwards and Simvastatin. MERCURY I17 trial reported 80% pa- Moore18 in their Meta analysis reported 9% increase tients in Rosuvastatin group achieving target LDL- in HDL with Rosuvastatin as compared to 8% with C as compared to 54% in Simvastatin group.
Simvastatin. McTaggart and Jones19 in their review Achieving the target LDL-C has been associated reported 8.5% rise in HDL-C in Rosuvastatin as with improved cardiovascular outcomes.5 In this compared to 6.4% in Simvastatin group. A very regard Rosuvastatin therapy may prove valuable modest rise in HDL-C is reported in DISCOVERY- Gomal Journal of Medical Sciences January-June 2010, Vol. 8, No. 1
Shimal Khan, et al.
Beta18 study both with Rosuvastatin (0.66%) and the Interdisciplinary Council on Reducing the Simvastatin (2.26%). This modest rise in HDL-C in Risk for Coronary Heart Disease, ninth Council DISCOVERY trial can be due to higher levels of meeting. Circulation 1999; 99: E1–E7.
HDL-C at baseline in these patients.
Pearson TA, Laurora I, Chu H, et al. The lipid In our study, Rosuvastatin was well tolerated treatment assessment project (L-TAP): a multi-centre survey to evaluate the percentages of with safety profile similar to Simvastatin, with no dyslipidemic subjects receiving lipid-lowering occurrence of serious adverse side effects. These therapy and achieving low-density lipoprotein findings are similar to those reported by other stud- goals. Arch Intern Med 2000; 160: 459–67.
Durrington P. The human and economic costs of under treatment with statins. Int J Clin Pract.
greater lipid modifying efficacy and goal attain- ment with a safety profile similar to that of Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Executive summary of the Third Report of the CONCLUSION
(NCEP) Expert Panel on Detection, Evaluation, statin is more efficacious in modifying lipid profile and Treatment of High Blood Cholesterol inAdults (Adult Treatment Panel III). JAMA 2001; and has comparable safety and adverse event pro- Brown WV, Bays HE, Hassman DR, et al. Efûcacy REFERENCES
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