OBJECTIVE: Statins reduce risk of cardiovascular disease through lowering of LDL-C (Low Density Lipoprotein cholesterol). We analyzed cost-effectiveness of statins in the reduction of serum LDL-C level among Korean population at high cardiovascular risk. METHODS: Rosuvastatin (5, 10, and 20 mg), atorvastatin (10, 20, 40, and 80 mg) and simvastatin (20, 40, and 80 mg) were included for the analysis, because those statins and doses were mostly prescribed in Korea. We determined effectiveness as % reduction of LDL cholesterol (LDL-C) levels per mg dose and % population reached to the ideal LDL-C level (<100 mg/dL), which is the target goal of LDL-C level for the high cardiovascular risk group as recommended by NCEP-ATP III guideline. The annual cost, which included overall cost for the drug price and management during follow up, was calculated. Average cost-effectiveness ratio (ACER) was calculated and used as the parameter representing cost-effectiveness of each statins. RESULTS: The lowest dose of each statins showed that achieving LDL-C target level was not high even in subjects showing relatively low basal LDL-C levels (<160 mg/dL). Also in case basal LDL-C level was over 160 mg/dL, the majority of statins were not sufficient to control LDL-C levels except atorvastatin 80 mg. In case of basal LDL-C level was lower than 160 mg/dl, atorvastatin 20 mg was the most cost-effective statin for LDL-C reduction regardless of considering basal LDL-C level. Simvastatin 40 mg was also cost-effective if basal LDL-C levels were between 100-129 mg/dL. CONCLUSIONS: For the reduction of LDL-C level in high risk subjects showing moderately elevated basal LDL-C level, atorvastatin 20 mg is the most cost-effective statin treatment strategy and then simvastatin 40 mg or rosuvastatin 10 mg was the second best option.
Cardiovascular Diseases ; Cholesterol, LDL ; Fluorobenzenes ; Follow-Up Studies ; Heptanoic Acids ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Lipoproteins ; Pyrimidines ; Pyrroles ; Simvastatin ; Sulfonamides ; Atorvastatin Calcium ; Rosuvastatin Calcium

BACKGROUND AND OBJECTIVES: Vasospastic angina is correlated with endothelial dysfunction. We compared endothelial function using flow-mediated vasodilatation (FMD) and circulating endothelial progenitor cells (EPCs) between patients with vasospasm and those without vasospasm and studied the effect of statin therapy on the changes of FMD and EPCs in vasospastic angina patients. SUBJECTS AND METHODS: In 133 patients who underwent an ergonovine provocation test, endothelial function was compared based on the presence or absence of spasm. The patients with coronary artery spasm (74 patients) were randomly assigned to either the 10 mg rosuvastatin group or the placebo group. We compared changes in the FMD and EPCs level for 6 months from the time of enrollment between the two groups. RESULTS: The incidence of cigarette smokers was higher in vasospastic angina patients than in those without spasm (p<0.001). The number of EPCs (68.6+/-36.1 vs. 103.7+/-39.3/200 microliter, p<0.001) and the FMD (7.1+/-4.5 vs. 8.6+/-3.6%, p=0.044) were significantly lower in patients with coronary artery spasm than in those without spasm. After 6 months of rosuvastatin treatment, the number of CD45(low)CD34(+) vascular endothelial growth factor receptor 2 (VEGFR2)(+) cells, which was defined as EPCs, increased significantly from 73.1+/-37.8/200 microliter to 99.1+/-37.8/200 microliter (p=0.002). The FMD was significantly ameliorated from 7.3+/-4.1 to 9.3+/-3.4% after 6 months of treatment (p<0.001). The FMD was correlated with the EPCs count before treatment (r=0.229, p=0.049) and after 6 months of treatment (r=0.268, p=0.020). CONCLUSION: The number of circulating EPCs and the FMD were reduced in vasospastic angina, and statin treatment increased the number of EPCs and the FMD. The EPCs level was correlated with the FMD.
Coronary Vasospasm ; Coronary Vessels ; Endothelium ; Ergonovine ; Fluorobenzenes ; Humans ; Incidence ; Prognosis ; Pyrimidines ; Spasm ; Stem Cells ; Sulfonamides ; Tobacco Products ; Vascular Endothelial Growth Factor Receptor-2 ; Vasodilation ; Rosuvastatin Calcium

BACKGROUND: Periprocedural treatment with high-dose statins is known to have cardioprotective and pleiotropic effects, such as anti-thrombotic and anti-inflammatory actions. We aimed to assess the efficacy of high-dose rosuvastatin loading in patients with stable angina undergoing off-pump coronary artery bypass grafting (OPCAB). MATERIALS AND METHODS: A total of 142 patients with stable angina who were scheduled to undergo surgical myocardial revascularization were randomized to receive either pre-treatment with 60-mg rosuvastatin (rosuvastatin group, n=71) or no pre-treatment (control group, n=71) before OPCAB. The primary endpoint was the 30-day incidence of major adverse cardiac events (MACEs). The secondary endpoint was the change in the degree of myocardial ischemia as evaluated with creatine kinase-myocardial band (CK-MB) and troponin T (TnT). RESULTS: There were no significant intergroup differences in preoperative risk factors or operative strategy. MACEs within 30 days after OPCAB occurred in one patient (1.4%) in the rosuvastatin group and four patients (5.6%) in the control group, respectively (p=0.37). Preoperative CK-MB and TnT were not different between the groups. After OPCAB, the mean maximum CK-MB was significantly higher in the control group (rosuvastatin group 10.7+/-9.75 ng/mL, control group 14.6+/-12.9 ng/mL, p=0.04). Furthermore, the mean levels of maximum TnT were significantly higher in the control group (rosuvastatin group 0.18+/-0.16 ng/mL, control group 0.39+/-0.70 ng/mL, p=0.02). CONCLUSION: Our findings suggest that high-dose rosuvastatin loading before OPCAB surgery did not result in a significant reduction of 30-day MACEs. However, high-dose rosuvastatin reduced myocardial ischemia after OPCAB.
Angina, Stable ; Coronary Artery Bypass ; Coronary Artery Bypass, Off-Pump ; Creatine ; Fluorobenzenes ; Humans ; Incidence ; Myocardial Ischemia ; Myocardial Revascularization ; Pyrimidines ; Risk Factors ; Sulfonamides ; Transplants ; Trinitrotoluene ; Troponin T ; Rosuvastatin Calcium

There is a tremendous amount of evidence about the beneficial roles of statins, as related to primary and secondary prevention, for patients with ischemic heart disease. Many cardiologists are prescribing these drugs to their patients regardless of the left ventricular systolic function, and especially for patients with old myocardial infarction. After the report on the post-hoc analysis of the Scandinavian Simvastatin Survival Study, there have been many reports about the roles of statins for the patients with heart failure from ischemic or non-ischemic etiologies. But most of these reports were non-randomized, observational, post-hoc subgroup analyses and small prospective short term studies, and the power of the evidence was too weak to set a guideline for statin therapy in patients with heart failure. The conclusions of the previous reports were that two large prospective randomized trials might shed light on choosing to administer statins. Last November, the COntrolled ROsuvastatin multiNAtional trial in heart failure (CORONA) study was presented and many cardiologists believed that this study did not resolve the lack of evidence for the current practice of administering statins to heart failure patients with ischemic heart disease, but it proved the safety of administering 10 mg of rosuvastatin. So, we review the potential benefits of statins, beyond the cholesterol lowering effects in patients with heart failure, and we will reexamine the use of statins in patients with heart failure after the CORONA study.
Cholesterol ; Fluorobenzenes ; Heart ; Heart Failure ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Light ; Myocardial Infarction ; Myocardial Ischemia ; Pyrimidines ; Secondary Prevention ; Simvastatin ; Sulfonamides ; Rosuvastatin Calcium

BACKGROUND AND OBJECTIVES: The mobilization of circulating endothelial progenitor cells (EPCs) might represent a useful strategy for the clinical therapy of ischemic heart disease. We examined the effect of early statin therapy before reperfusion therapy on the circulating EPCs during the acute phase in patients with acute myocardial infarction (AMI). SUBJECTS AND METHODS: A total of 84 consecutive AMI patients undergoing primary percutaneous coronary intervention (PCI) within 24 hours of pain onset were included in this study. We randomly divided the patients into 3 groups according to rosuvastatin therapy before PCI: the control group (n:27, 19 males and 8 females, 58+/-2 years of age), the rosuvastatin 10 mg group (n: 28, 21 males and 7 females, 58+/-3 years of age) and the 40 mg group (n: 29, 23 males and 6 females, 59+/-2 years of age). The circulating EPCs and high sensitivity C-reactive protein (hs-CRP) levels were analyzed on admission and at 1, 3, 5, 7 and 30 days after PCI. The circulating EPCs were measured by flow cytometry as the CD45(low)CD34+VEGFR2+ cells. RESULTS: The circulating EPCs peaked on day 3 after PCI, whereas the increment of circulating EPCs was significantly suppressed in the rosuvastatin 10 mg and 40 mg groups compared with the control group on day 3 (control vs rosuvastatin 10 mg vs rosuvastatin 40 mg: 0.072% vs 0.067% vs 0.061%, respectively, p=0.002) and day 5 (0.068% vs 0.060% vs 0.058%, respectively, p=0.029). The level of hs-CRP markedly increased from day 1 and this peaked on day 3 after PCI. Early statin therapy significantly suppressed the elevation of hs-CRP compared with the control group on day 1 (24.36 mg/L vs 17.88 mg/L vs 13.08 mg/L, respectively, p=0.035) and on day 3 (30.15 mg/L vs 22.78 mg/L vs 17.16 mg/L, respectively, p=0.034). There was a statistically significant correlation between the circulating EPCs and the hs-CRP (r=0.349, p=0.007). CONCLUSION: In the AMI patients, the early stain therapy before reperfusion therapy didn't increase the mobilization of circulating EPCs, but it suppressed the elevation of hs-CRP. This data suggests that the mobilization of circulating EPCs may be related to systemic inflammation during the acute phase in patients with AMI.
C-Reactive Protein ; Female ; Flow Cytometry ; Fluorobenzenes ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammation ; Male ; Myocardial Infarction ; Myocardial Ischemia ; Percutaneous Coronary Intervention ; Pyrimidines ; Reperfusion ; Stem Cells ; Sulfonamides ; Rosuvastatin Calcium

Aged ; Female ; Fluorobenzenes ; therapeutic use ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; Polymorphism, Genetic ; genetics ; Pyrimidines ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; therapeutic use

OBJECTIVE: C-reactive protein (CRP), lipoprotein (a)[Lp(a)], and fibrinogen are associated with systemic inflammatory reactions. Statins have anti-inflammatory effects. However, the effect of statins on these parameters is inconsistent. We evaluated the effect of statins on inflammatory markers and variables related to changes in these markers. METHODS: A total of 390 hypercholesterolemic patients were enrolled. Atorvastatin (n=112), lovastatin (n=25), pitavastatin (n=49), rosuvastatin (n=20), and simvastatin (n=184) were administered. Lipids, CRP, Lp(a), and fibrinogen levels were measured before and after 2 months of the therapy. RESULTS: Statins reduced cholesterol, low density lipoprotein (LDL) cholesterol, and triglyceride levels by -28.9+/-9.1% (P=0.000), -41.4+/-12.4% (P=0.000), and -11.6+/-39.4% (P=0.000), respectively and increased high density lipoprotein (HDL) cholesterol level by 2.56+/-13.2% (P=0.014). CRP levels decreased from 1.23+/-1.30 to 1.14+/-1.29 mg/L (P=0.000). Lp(a) levels were not changed (P=0.91) and fibrinogen levels increased from 277.8+/-54.4 to 282.6+/-56.9 mg/dL (P=0.042). Changes in CRP levels were associated with baseline CRP levels (r=-0.56, P=0.000) and changes in HDL cholesterol levels (r=-0.14, P=0.005). Changes in Lp(a) levels were associated with changes in triglyceride (r=-0.24, P=0.000) and baseline aspartate aminotransferase level (r=0.12, P=0.015). Changes in fibrinogen levels were associated with baseline fibrinogen levels (r=-0.40, P=0.000), sex (r=0.18, P=0.001), and changes in HDL cholesterol levels (r=-0.15, P=0.003). CONCLUSION: Inflammatory markers showed different responses to statins and changes in these markers were associated with different parameters. This finding suggests that anti-inflammatory effect of statin is confined to a specific pathway of inflammation.
Aspartate Aminotransferases ; C-Reactive Protein ; Cholesterol ; Cholesterol, HDL ; Fibrinogen ; Fluorobenzenes ; Heptanoic Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammation ; Lipoprotein(a) ; Lipoproteins ; Lovastatin ; Pyrimidines ; Pyrroles ; Quinolines ; Simvastatin ; Sulfonamides ; Atorvastatin Calcium ; Rosuvastatin Calcium

BACKGROUND/AIMS: In a previous study, statin therapy reduced proteinuria and ameliorated the progression of chronic kidney disease. However, in patients with chronic renal failure (CRF), the beneficial effect of statin therapy on the preservation of renal function has not been determined. Thus, we determined the effect of rosuvastatin on CRF. METHODS: Male Sprague-Dawley rats (6 weeks old) were subjected to 5/6 nephrectomy. Six weeks after the procedure, the rats were divided into control and rosuvastatin-treated groups. Body weight and blood/urine biochemical parameters were measured 6 weeks after 5/6 nephrectomy and 8 weeks after the start of rosuvastatin treatment. Remnant kidneys were harvested at 6 (n = 4) and 14 (n = 8) weeks after 5/6 nephrectomy. RESULTS: During rosuvastatin treatment, changes in body weight and serum total and low-density lipoprotein cholesterol did not differ significantly between the control and rosuvastatin-treated groups. Although serum creatinine and proteinuria increased in both groups, the differences were not significant (p = 0.24 and 0.77, respectively). Immunohistochemical staining, enzyme-linked immunosorbent assays, and western blotting showed that the expression of transforming growth factor-beta1 and intracellular adhesion molecule-1 were reduced in the rosuvastatin-treated group. CONCLUSIONS: Long-term statin treatment may attenuate the inflammatory process in the progression of renal failure.
Animals ; Blotting, Western ; Body Weight ; Cholesterol ; Creatinine ; Enzyme-Linked Immunosorbent Assay ; Fluorobenzenes ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Kidney ; Kidney Failure, Chronic ; Lipoproteins ; Male ; Nephrectomy ; Proteinuria ; Pyrimidines ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Sulfonamides ; Rosuvastatin Calcium

BACKGROUND/AIMS: In a previous study, statin therapy reduced proteinuria and ameliorated the progression of chronic kidney disease. However, in patients with chronic renal failure (CRF), the beneficial effect of statin therapy on the preservation of renal function has not been determined. Thus, we determined the effect of rosuvastatin on CRF. METHODS: Male Sprague-Dawley rats (6 weeks old) were subjected to 5/6 nephrectomy. Six weeks after the procedure, the rats were divided into control and rosuvastatin-treated groups. Body weight and blood/urine biochemical parameters were measured 6 weeks after 5/6 nephrectomy and 8 weeks after the start of rosuvastatin treatment. Remnant kidneys were harvested at 6 (n = 4) and 14 (n = 8) weeks after 5/6 nephrectomy. RESULTS: During rosuvastatin treatment, changes in body weight and serum total and low-density lipoprotein cholesterol did not differ significantly between the control and rosuvastatin-treated groups. Although serum creatinine and proteinuria increased in both groups, the differences were not significant (p = 0.24 and 0.77, respectively). Immunohistochemical staining, enzyme-linked immunosorbent assays, and western blotting showed that the expression of transforming growth factor-beta1 and intracellular adhesion molecule-1 were reduced in the rosuvastatin-treated group. CONCLUSIONS: Long-term statin treatment may attenuate the inflammatory process in the progression of renal failure.
Animals ; Blotting, Western ; Body Weight ; Cholesterol ; Creatinine ; Enzyme-Linked Immunosorbent Assay ; Fluorobenzenes ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Kidney ; Kidney Failure, Chronic ; Lipoproteins ; Male ; Nephrectomy ; Proteinuria ; Pyrimidines ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Sulfonamides ; Rosuvastatin Calcium

BACKGROUND: In order to evaluate the factors of compliance with a lipid lowering therapy, a prospective observational study of patients with hypercholesterolemia using rosuvastatin was carried out. METHODS: A total of 2,607 patients who were newly prescribed rosuvastatin were enrolled from 32 family physicians in Korea from March 2009 to December 2009. Of them, 301 patients were excluded due to incomplete data or follow-up compliance data. The patients were regularly observed to ascertain the compliance associated with rosuvastatin at intervals of 12 and 24 weeks. We collected risk factors for the compliance using a structured questionnaire. The criteria for evaluating compliance are to measure clinic attendance, to assess the continuity of therapy, and to calculate the percentage of doses taken. RESULTS: Among a total of 2,306 patients, the degree of compliance was 54.1%. According to logistic regression analysis, the factors for compliance with the lipid lowering drug included old age (odds ratio [OR], 2.68; 95% confidence interval [CI], 2.09 to 3.45), frequent exercise (OR, 1.76; 95% CI, 1.43 to 2.18), previous statin therapy (OR, 4.02; 95% CI, 3.22 to 5.01), hypertension (OR, 1.80; 95% CI, 1.48 to 2.19), diabetes mellitus (OR, 2.20; 95% CI, 1.69 to 2.87), concomitant medication (OR, 2.28; 95% CI, 1.88 to 2.77), and high coronary heart disease (CHD) risk category (OR, 1.82; 95% CI, 1.39 to 2.38). The compliance decreased with high low density lipoprotein cholesterol levels (OR, 0.20; 95% CI, 0.16 to 0.26). CONCLUSION: The compliance of patients using rosuvastatin was 54.1% in primary care. The factors related to higher compliance were old age, regular exercise, previous statin therapy, concomitant medication, presence of hypertension or diabetes, and higher CHD risk level.
Cholesterol ; Cholesterol, LDL ; Compliance ; Coronary Disease ; Diabetes Mellitus ; Fluorobenzenes ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Hypertension ; Korea ; Lipoproteins ; Logistic Models ; Physicians, Family ; Primary Health Care ; Prospective Studies ; Pyrimidines ; Risk Factors ; Sulfonamides ; Rosuvastatin Calcium ; Surveys and Questionnaires