coenzyme-A Reductase Inhibitors Research Articles

Routine statin treatment after acute coronary syndromes?

Am Heart J 2002;143:940-2.

A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme a-reductase inhibitors simvastatin and atorvastatin

Background: Neural networks have been used in diagnosing and treating many diseases, including the diagnosis of myocardial infarction and insulin dosing in diabetes mellitus. Objective: The goal of this study was to develop a preliminary pharmacodynamic model for dosing of the hydroxymethylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors simvastatin and atorvastatin using neural network analysis. Methods: Using NeuralSIM neural network software (NeuralWare, Carnegie, Pa), lipid panels from patients at a hospital lipid clinic were entered as inputs for the model, and the doses of simvastatin or atorvastatin that achieved those lipid results were used as outputs. The network was trained using 2 different data sets and was run using a subset of the data as inputs. The results of the neural network run (predictions) were compared with the actual doses used as directed by the hospital pharmacist in accordance with the lipid clinic protocol. Results: Complete data sets were available for 17 patients (11 men, 6 women). The mean age of these patients was 56.7 years (range, 40–67 years). The neural network model based on data set 1 predicted a dose that was within 95% of the actual dose 7 of 12 times and predicted use of the drug actually used 13 of 19 (68.4%) times. The neural network based on data set 2 predicted use of the drug actually used 10 of 17 (58.8%) times, but the predicted doses never approximated the actual doses by ≥90%. Conclusions: A neural network model for the dosing of the HMG-CoA-reductase inhibitors simvastatin and atorvastatin demonstrated an ability to predict appropriate dosing, but inclusion of other factors (eg, age, body weight, sex) and a larger sample size may be necessary for development of a more accurate model.

Effects of simvastatin (40 and 80 mg) on highly sensitive C-reactive protein in patients with combined hyperlipidemia

C-reactive protein (CRP), a member of the pentraxin family, is a prototypic marker of inflammation. The interest in CRP with regards to cardiovascular risk assessment has been ushered in with the ultrasensitive or highly sensitive assays. Numerous prospective studies have now confirmed that highly sensitive CRP (hsCRP) in normal volunteers predicts cardiovascular events. 1‐5 Also, hsCRP appears to be additive to an elevated total cholesterol/high-density lipoprotein (HDL) cholesterol ratio in men and women. 3,4 Hydroxymethylglutaryl coenzyme-A reductase inhibitors (statins) possess anti-in flammatory properties and reduce CRP levels. 6 ‐8 However, these studies indicate that the reduction in CRP levels by statins may be independent of their low-density (LDL) lowering effects. 6 ‐8 Despite these findings, there have been few data evaluating whether the reduction in CRP levels with statins is dose dependent. 9 Thus, we undertook the present study to determine if there was a dose-response effect of simvastatin on CRP levels. ••• This was a placebo-controlled, dose-response

Strategies for minimizing hyperlipidemia after cardiac transplantation.

Allograft coronary artery disease represents a major limitation to long-term survival after cardiac transplantation. Hyperlipidemias have been linked to the development of native coronary atherosclerosis, and hyperlipidemic states have correlated with the severity of allograft coronary artery disease. Heart transplant recipients typically manifest increases in plasma levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months following transplantation. Factors known to promote post-transplant hyperlipidemia include the use of corticosteroids, cyclosporine (interference with clearance and increased oxidizability of LDL), sirolimus (hypertriglyceridemia), and patient-specific causes of hyperlipidemia which contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors are the foundation of antilipid therapy following cardiac transplantation. Pravastatin is effective in lowering plasma cholesterol levels and is associated with a decreased incidence and progression of allograft coronary artery disease. All HMG-CoA reductase inhibitors except pravastatin are metabolized by the hepatic cytochrome P450 system which metabolizes cyclosporine, increasing the risk of myostitis when they are used in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin have been studied in heart transplant recipients. Gemfibrozil has proved effective in transplant recipients when there is isolated marked elevation of plasma triglyceride levels. When hyperlipidemia persists despite therapy, some benefit may result with conversion from cyclosporine to tacrolimus. Although a definitive link between hyperlipidemia and allograft coronary disease has yet to be proven, available evidence points to abnormal lipid metabolism as part of the complex etiologic machinery driving the process of 'chronic rejection'. Consensus exists within the transplant community that a HMG-CoA reductase inhibitor such as pravastatin, should be part of the routine post-transplant drug regimen, and persistent hyperlipidemia should be aggressively treated.

Embolism from the Aorta: Atheroemboli and Thromboemboli.

To date, there are no evidence-based data to support specific drug therapy for a patient with atheroembolism. It makes sense to use HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (statins) in any patient with atherosclerosis, as these drugs have been shown to reduce the risk of myocardial infarction and stroke, and have a theoretical benefit on plaque stabilization. Surgical treatment should be considered for patients with abdominal aortic or popliteal artery aneurysms and downstream atheroembolism. There are case reports of atheroemboli in patients worsening after given warfarin or heparin. For this reason, some institutions are reluctant to prescribe these drugs for patients with atheroemboli or thromboemboli from aortic plaque. However, the incidence of this complication is quite low. Anticoagulation probably should be stopped if a patient develops atheroembolism. Similarly, the current state of knowledge does not allow for selecting specific pharmacologic intervention in patients with thromboemboli from aortic plaque. Statin therapy does make sense, as these drugs theoretically stabilize plaques and prevent plaque hemorrhage, thrombosis, and subsequent embolization. Unstable aortic plaques may develop superimposed thrombi (red thrombi on pathologic examination), easily seen as mobile elements on transesophageal echocardiography. Therefore, it is possible that anticoagulation with warfarin might prevent embolic events in these patients. For this reason, we are often in the position of recommending warfarin therapy for patients with emboli and severe atheromas seen on transesophageal echocardiography, especially when superimposed mobile thrombi are seen. There are small series in the literature that indicate the potential benefit of warfarin. However, until a large multicenter randomized clinical trial is done, the use of warfarin can not be definitively recommended. Antiplatelet agents, although safer than warfarin (less risk of hemorrhage), have not been proven beneficial in patients with thromboembolism from the aorta. Surgery (endarterectomy) of the aortic arch is a very risky procedure that should not be performed routinely, but may be used in highly selected patients.

Cholesterol-lowering therapy for smokers and non-smokers: a life-table analysis

The advent of 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) has revolutionised treatment of high blood-plasma cholesterol concentrations. But, because of the high prevalence of hypercholesterolaemia and the high costs of statins, their indiscriminate use in primary prevention poses financial difficulties. 1 The Sheffield risk tables, intended to guide risk management of hypercholesterolaemia in healthy people by absolute risks for coronary disease, are determined by age, sex, and risk-factor status. 2,3 These and similar calculations of absolute risk are based on the Framingham Heart Study (FHS) functions, 4 and their use has been increasingly advocated to target lipidlowering therapy. 3,5–8

The role of fibric acid derivatives in the secondary prevention of coronary heart disease.

Fibric acid derivatives effectively lower triglycerides and raise high-density lipoprotein (HDL) cholesterol, but their effect on low-density lipoprotein (LDL) cholesterol is weakly beneficial (small decreases) to adverse (small increases) and varies according to the triglyceride level. Early primary prevention studies of atherosclerosis using the fibric acid derivative clofibrate showed only modest effects on atherosclerosis and an alarming increase in mortality in the intervention group. Although the Helsinki Heart Study later demonstrated that gemfibrozil decreased cardiac endpoints in primary prevention without increasing total mortality, the efficacy of fibric acid derivatives in both primary and secondary prevention of atherosclerosis has remained widely in doubt. Nevertheless, many patients with atherosclerosis have normal or even low LDL cholesterol, but elevated triglyceride, and low HDL cholesterol; furthermore, even aggressive LDL cholesterol lowering with HMG Co-A (3-hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) fails to prevent the majority of atherosclerotic events. These findings have kindled increased interest in the use of fibric acid derivatives in atherosclerosis prevention, especially through treatment of non-LDL dyslipidemias. Recent studies with angiographic and clinical end-points have now provided evidence for a beneficial effect of at least some drugs in this class in the secondary prevention of atherosclerosis.

Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae.

In patients with atherosclerosis, hepatic hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitors may reduce the activation of inflammation. Because Chlamydia pneumoniae infection has been linked to coronary artery disease through the induction of plaque inflammation, we investigated whether cerivastatin affects the infection rate of human macrophages and endothelial cells (ECs) and their proinflammatory activation after chlamydial infection. Macrophages were collected from the alveolar compartment of 6 volunteers and 10 patients with chronic bronchitis. ECs were obtained from 10 umbilical cords. The C. pneumoniae strain CWL was incubated with macrophages or ECs in the presence and absence of the CSE inhibitor cerivastatin. The infection rate was determined by immunofluorescence microscopy. The release of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor (TNF)-alpha was quantified by ELISA. The release of oxygen radicals was determined by ferricytochrome assay. Infection rates were tendentially lower after the preincubation of macrophages with CSE inhibitors (17.2% versus 9. 3% and 18.2% versus 10.4%, respectively; P=NS). The secretion of MCP-1, IL-8, and TNF-alpha by infected macrophages from volunteers increased. Coincubation with cerivastatin resulted in significantly lower MCP-1 and IL-8 production, whereas the release of TNF-alpha remained unaffected. Similar effects regarding chemokine release were observed in ECs. CSE inhibitors modify the inflammatory response of human immune cells to C. pneumoniae. This finding could be relevant for the therapeutic potential of CSE statins in patients with atherosclerosis and C. pneumoniae infection.

Lovastatin Inhibits α-Farnesene Synthesis without Affecting Ethylene Production during Fruit Ripening in `Golden Supreme' Apples

Lovastatin is a specific hydroxymethylglutaryl coenzyme-A reductase inhibitor in animals and as such, is a potent cholesterol lowering pharmaceutical for human use. Because it has also been shown to inhibit α-farnesene in certain plants, we investigated its effects on ethylene and α-farnesene biosynthesis, volatile production, and fruit color during ripening in `Golden Supreme' apples [Malus sylvestris (L.) Mill. var. domestica (Borkh.) Mansf.]. Immediately after harvest, fruit were dipped in Lovastatin solution for 2 min, allowed to dry, and stored in the dark at 20 °C for 30 days. Internal ethylene at harvest was low (< 0.1 mL·L-1) and α-farnesene was undetectable. Both internal ethylene and α-farnesene increased in nontreated fruit during 30 days storage. Prestorage Lovastatin treatment did not affect ethylene synthesis, but at 1.25 or 2.5 mmol·L-1 nearly eliminated α-farnesene production. At 0.25 mmol·L-1, Lovastatin delayed the increase in α-farnesene production about 12 days and reduced total α-farnesene production by the end of storage compared with controls. When applied to nontreated preclimacteric fruit, ethephon at 1.4 mmol·L-1 increased both internal ethylene concentration and α-farnesene production. In Lovastatin-treated preclimacteric fruit, however, ethephon increased internal ethylene concentration without promoting α-farnesene synthesis. In another trial, after 30 days storage at 0 °C, fruit were treated with 1.25 mmol·L-1 Lovastatin and stored at 20 °C with air circulation for 20 days. These fruit accumulated similar amounts of ethylene as nontreated controls, but α-farnesene production decreased rapidly and was not detectable after 5 days. Treating with ethephon at 1.4 mmol·L-1 increased α-farnesene production in control fruit but not in Lovastatin-treated fruit. Lovastatin treatment did not affect the change in fruit color. Chemical names used: [1S-[1α (R °), 3α, 7β, 8β (2S °, 4S °), 8ab]]-1,2,3,7,8,8α-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthaienyl 2-methylbutanoate (Lovastatin); 2-chloroethylphosphonic acid (ethephon).

Which statin is most efficient for the treatment of hypercholesterolemia? a cost-effectiveness analysis

A review of the cost-effectiveness literature indicated that the hydroxymethylglutaryl coenzyme A-reductase inhibitor fluvastatin is more cost-effective for achieving minorto-moderate reductions in low-density lipoprotein cholesterol (LDL-C) levels than 3 other statins: lovastatin, pravastatin, and simvastatin. The main goal of this study was to verify the applicability of these conclusions to Spanish health care costs and patterns of resource consumption related to the treatment of hypercholesterolemia. A stochastic simulation model was used to predict both the costs and effects of treating high-risk hypercholesterolemic patients with fluvastatin, lovastatin, pravastatin, or simvastatin. Epidemiologic data were used to find a suitable theoretic probability distribution model for baseline LDL-C values in high-risk hypercholesterolemic patients. The model was then used to generate 10,000 random observations of baseline LDL-C values; the corresponding LDL-C values after a 2-year treatment period were predicted as a function of the baseline value and the percentage reduction expected with a particular statin and dose, according to the results obtained in 2 meta-analyses. The probability of treatment discontinuation was also taken into account using estimates obtained in usual practice. The effects of treatment were expressed as the rate of success in achieving the goal level of LDL-C, as defined in the current Spanish recommendations for the treatment of hypercholesterolemia. The average costs of treatment were computed from both the social and public-financing perspectives, including the cost of lipid-lowering drugs, physician visits, laboratory tests, and days off work, as appropriate. The occurrence of nonscheduled visits and workdays lost because of side effects were taken into account to compute indirect costs relevant to the social perspective. The potential costs of treating side effects were ignored. A costeffectiveness analysis was performed to compare the cost-effectiveness ratios obtained with each of the 4 statins considered in this study. Model-based predictions of the effects, total costs, and cost-effectiveness ratios were made. Cost-effectiveness ratios were interpreted as the cost per patient meeting the goal of therapy, according to current Spanish recommendations. The data showed that fluvastatin had the lowest cost-effectiveness ratios when LDL-C levels required reduction to ≤25% of baseline levels. In this situation, fluvastatin was more cost-effective than lovastatin, pravastatin, or simvastatin from public-financing and social perspectives.

Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation

Increased atherosclerosis risk in hyperlipidemic patients may be a result of the enhanced oxidizability of their plasma lipoproteins. We have previously shown that hypocholesterolemic drug therapy, including the 3-hydroxy-3-methyl-glutaryl CoenzymeA (HMG-CoA) reductase inhibitors, and the hypotriglyceridemic drug bezafibrate, significantly reduced the enhanced susceptibility to oxidation of low density lipoprotein (LDL) isolated from hyperlipidemic patients. Although this antioxidative effect could not be obtained in vitro with all of these drugs, the active drug metabolites, which are formed in vivo, could affect lipoprotein oxidizability. We thus sought to analyze the effect of atorvastatin and gemfibrozil, as well as specific hydroxylated metabolites, on the susceptibility of LDL, very low density lipoprotein (VLDL), and high density lipoprotein (HDL) to oxidation. LDL oxidation induced by either copper ions (10 microM CuSO4), by the free radical generator system 2'-2'-azobis 2-amidino propane hydrochloride (5 mM AAPH), or by the J-774A.1 macrophage-like cell line, was not inhibited by the parent forms of atorvastatin or gemfibrozil, but was substantially inhibited (57-97%), in a concentration-dependent manner, by pharmacological concentrations of the o-hydroxy and the p-hydroxy metabolites of atorvastatin, as well as by the p-hydroxy metabolite (metabolite I) of gemfibrozil. On using the atorvastatin o-hydroxy metabolite and gemfibrozil metabolite I in combination an additive inhibitory effect on LDL oxidizability was found. Similar inhibitory effects (37-96%) of the above metabolites were obtained for the susceptibility of VLDL and HDL to oxidation in the oxidation systems outlined above. The inhibitory effects of these metabolites on LDL, VLDL, and HDL oxidation could be related to their free radical scavenging activity, as well as (mainly for the gemfibrozil metabolite I) to their metal ion chelation capacities. In addition, inhibition of HDL oxidation was associated with the preservation of HDL-associated paraoxonase activity. We conclude that atorvastatin hydroxy metabolites, and gemfibrozil metabolite I possess potent antioxidative potential, and as a result protect LDL, VLDL, and HDL from oxidation. We hypothesize that in addition to their beneficial lipid regulating activity, specific metabolites of both drugs may also reduce the atherogenic potential of lipoproteins through their antioxidant properties.

Endothelial dysfunction in streptozotocin-diabetic rats is not reversed by dietary probucol or simvastatin supplementation.

Oxidative stress and dyslipidaemia are key features of diabetes mellitus and may be involved in mediating the vascular endothelial dysfunction associated with this disease. The aim of this study was to examine the effect of dietary lipid-lowering and antioxidant agents on vascular endothelial function and oxidative stress. Diabetic male Sprague-Dawley rats (i.v. streptozotocin, 45 mg/kg) were fed for 4 weeks on a standard diet or on a diet supplemented with either the lipid-lowering antioxidant probucol (1% w/w in diet) or the 3-hydroxy 3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor simvastatin (0.01% w/w in diet). Responses to noradrenaline, acetylcholine, and sodium nitroprusside were assessed in small mesenteric arteries (mean internal diameter 300+/-5 microm, n = 80) mounted on a small vessel myograph. Plasma concentrations of total cholesterol and triglycerides were significantly raised in standard-fed diabetic rats and significantly reduced in probucol and simvastatin-fed diabetic rats 8-epi-prostaglandin (PG)F2alpha, an indicator of oxidative stress, was raised in liver and aorta from diabetic rats compared to controls. Probucol supplementation reduced 8-epi-PGF2alpha in aorta and liver of diabetic rats but increased 8-epi-PGF2alpha content in plasma and aorta from control animals. The abnormal relaxation to acetylcholine in arteries from the diabetic rats (pEC550 diabetic 6.763+/-0.172 vs control 7.541+/-0.175; p < 0.05) was not improved by probucol or simvastatin. These data, therefore, do not support a role for oxidative stress or dyslipidaemia in mediating the impaired ACh-induced endothelium-dependent relaxation of small mesenteric arteries from the streptozotocin-diabetic rat.

Effect of fluvastatin for safely lowering atherogenic lipids in renal transplant patients receiving cyclosporine

The lipophilic 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors have been associated with rhabdomyolysis in cyclosporinetreated patients, indicating an interaction of drugs. We therefore studied the safety and efficacy of the hydrophilic HMG-CoA reductase inhibitor fluvastatin in 14 cyclosporine-treated renal transplant patients. To qualify for inclusion, total cholesterol after dietary stabilization had to be >240 mg/dl. Prior to starting active medication, patients underwent a 4-week placebo period. Fluvastatin was given in a dose of 20 mg once daily for 12 weeks, which was increased to 20 mg twice daily for a further 8 weeks. Fluvastatin reduced total and low density lipoprotein cholesterol in all patients at both dosages whereas no effect on high density lipoprotein cholesterol was observed. Triglyceride levels were lowered at week 20. Incremental dosages of fluvastatin did not affect cyclosporine concentration and no adjustment of cyclosporine dosage was necessary. The higher doses of fluvastatin also had no effect on renal function as judged by serum creatinine levels. Creatine phosphokinase remained unchanged throughout the study. No serious side-effects were observed. In conclusion, the hydrophilic HMG-CoA reductase inhibitor fluvastatin at either 20 or 40 mg /day appears to be both safe and effective in lowering atherogenic lipids in renal transplant patients.

Effect of fluvastatin for safely loweringatherogenic lipids in renal transplant patients receiving cyclosporine

The lipophilic 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors have been associated with rhabdomyolysis in cyclosporinetreated patients, indicating an interaction of drugs. We therefore studied the safety and efficacy of the hydrophilic HMG-CoA reductase inhibitor fluvastatin in 14 cyclosporine-treated renal transplant patients. To qualify for inclusion, total cholesterol after dietary stabilization had to be >240 mg/dl. Prior to starting active medication, patients underwent a 4-week placebo period. Fluvastatin was given in a dose of 20 mg once daily for 12 weeks, which was increased to 20 mg twice daily for a further 8 weeks. Fluvastatin reduced total and low density lipoprotein cholesterol in all patients at both dosages whereas no effect on high density lipoprotein cholesterol was observed. Triglyceride levels were lowered at week 20. Incremental dosages of fluvastatin did not affect cyclosporine concentration and no adjustment of cyclosporine dosage was necessary. The higher doses of fluvastatin also had no effect on renal function as judged by serum creatinine levels. Creatine phosphokinase remained unchanged throughout the study. No serious side-effects were observed. In conclusion, the hydrophilic HMG-CoA reductase inhibitor fluvastatin at either 20 or 40 mg /day appears to be both safe and effective in lowering atherogenic lipids in renal transplant patients.

Clinical perspectives on primary and secondary prevention of coronary atherosclerosis

Several clinical trials have provided compelling evidence in support of the benefits of lipid-lowering therapy for primary and secondary prevention of atherosclerosis. The results of primary prevention trials have demonstrated that coronary morbidity can be reduced and survival improved with effective lipid-lowering regimens. There has been concern, however, regarding harmful effects (e.g., increased rate of suicide and increased risk of gastrointestinal cancer) of cholesterol-lowering therapies in primary prevention trials. These concerns are not well supported by strong evidence, and there has been lack of a dose-response relationship. It is generally believed that for 1% reduction in serum cholesterol, there is a 2% reduction in the risk of coronary events. The results of numerous secondary prevention trials have clearly demonstrated the benefit of lipid-lowering therapies in reducing the risk of future cardiac events and cardiac mortality in patients with preexistent coronary artery disease. Several studies have shown that treatment regimens effective in reducing LDL cholesterol levels lead to regression of atherosclerotic plaques as well as retard the progression of the disease process. Interestingly, some of these studies have also shown that when measured angiographically, the luminal diameter at the site of stenotic lesions might improve only by an average of 2% to 3%; however, this small degree of improvement is associated with a remarkable reduction by 35% to 25% in the risk of future coronary events. These findings further corroborate the hypothesis about the importance of a lipid-rich cap of the vulnerable plaques and suggest that the reduction in lipid levels is associated with the efflux of lipids from the plaque, thus converting it from a vulnerable to a stable state. The most recent data from the 4S trial have unequivocally demonstrated the benefits of treatment with HMG coenzyme-A reductase inhibitors in reducing the risk of future coronary events and improving the overall survival in patients with established CHD. Although there is still ongoing controversy regarding the precise course of action for primary prevention of CHD, the results of a large number of studies provide overwhelming evidence in support of aggressive lipid-lowering therapy for secondary prevention of CHD. Based on the findings of these studies, it seems prudent that clinicians become actively involved in the evaluation and management of lipid abnormalities and other risk factors in patients with CHD.

HMG CoA reductase inhibitors

HMG CoA (β-hydroxy-β-methylglutaryl coenzyme A) reductase inhibitors are very effective in lowering total and low-density lipoprotein cholesterol. The incidence of adverse effects is very low with elevated transaminase levels and myopathy being of greatest concern. Administration of these drugs in c

Efficacy and Safety of Fluvastatin Sodium XL 80mg in Treatment of Hypercholesterolemic Patient with Risk Factor of Cardiovascular Disease

Back ground: Reduction of coronary heart disease (CHD) risk through the modification of risk factors has a strong effect on clinical practice. The introduction of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors (statins) has significantly advanced the treatment of hypercholesterolemia and in reduction of cardiovascular events and total mortality rates. Among the available statins, Fluvastatin is a newer, synthetic, second generation, potent lipid lowering agent and widely accepted in diverse population. However the safety profile and efficacy was not assessed in Bangladeshi population, a population significantly different from Caucasian population where most studies were done. Current study aimed at evaluating the safety and efficacy of fluvastatin in the specified population. Methods: The study is an open-label, multicenter, quasi experimental study conducted among 162 adult patients suffering from hypercholesterolemia. After through baseline evaluation, the patients were given with Fluvastatin 80 mg once daily for 3 months. All the patients were assessed twice, before and after treatment. Data on demography, of relevant medical history and of physical examination were collected in the both the visit along with data on relevant lipid parameters (Total Cholesterol, LDL-C, HDL-C and TG) were collected at final visit. Safety was assessed by evaluating adverse events, as well as laboratory abnormalities, including liver aminotransferases. Results: Serum total cholesterol was found to be significantly reduced and across two assessments the reduction was 51.2 units (P&lt;.001). Average reduction in LDL-cholesterol was around 40 units (P&lt;.001). Most significant reduction (140.0±305.8 units) was seen in serum LDL cholesterol (P&lt;.001). However; no statistically significant reduction was seen in HLD cholesterol. Safety of fluvastatin was assessed by evaluating the adverse events, as well as through laboratory abnormalities, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Comparison of aminotransferase level was done before and after treatment through paired t test, Neither ALT nor the AST showed statistically significant rise after 3 months treatment of fluvastatin (P&gt;.05). Out of 162 study participant 4.3% had their treatment interrupted, of which 1 (0.62%) had to cease treatment due to lack of efficacy, 1 (0.62%) experienced adverse event, 2 (1.24%) didn’t return to follow-up and 3 (1.86%) patients requested their physician to cease the treatment. Conclusion: Three month treatment with Fluvastatin XL 80 mg reduces most of lipid parameter of lipid profile (Total cholesterol, Triglyceride and LDL) significantly. The drug is found to be well tolerated with minimal adverse event during the course of treatment. Key words: Hypercholesterolemia; Dyslipidemia; Lipid lowering agent; Fluvastatin. DOI: 10.3329/cardio.v2i2.6631Cardiovasc. j. 2010; 2(2) : 147-155