Low-dose Simvastatin Research Articles

The Change of Cholesterol Level and IL-6, CRP in Unstable Angina Patients with Hypercholesterolemia after Low Dose Simvastatin Therapy

Background and Objectives：Cardiovascular mortality in patients with atherosclerosis can be reduced by treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors. This proven effect is probably due, not only to the cholesterol lowering effect, but also to the non-lipid-lowering mechanisms elicited by the action of statins. These results, however, were achieved with high or usual doses of statin therapy, whereas similar results with low dose statins are rare. The aims of this study wereas to investigate the changes ofin cholesterol level and the inflammatory markers, Interleukin-6 (IL-6, and C-Reactive protein (CRP, in unstable angina patients with hypercholesterolemia, using low dose simvastatin therapy. Subjects and Methods：Eighteen unstable angina patients (55±6 years, M：F＝10：8, Baunwald class IIIb with hypercholesterolemia (a LDL-cholesterol level over 100 mg/dLwere evaluated. A Llow dose of simvastatin (5 mg was administrated for 4 weeks. The changes of total cholesterol, LDL-cholesterol, triglyceride, HDL-cholesterol and the inflammatory markers, IL-6, and CRP, were all elevated from the baseline following 4 weeks of treatment. Results：The baseline mean values of total cholesterol, LDL-cholesterol, triglyceride, and HDL-cholesterol were 237.1±56.9 mg/dL, 131.9±39.0 mg/dL, 168.3±20.4 mg/dL, and 50.0±3.8 mg/dL, respectively. The baseline mean values of IL-6 and hs CRP were 6.842±6.661 pg/mL, and 0.866±1.083 mg/dL, respectively. Following the 4 weeks of simvastatin treatment, the levels of total cholesterol, LDL- cholesterol, triglyceride, and HDL-cholesterol were 200.8±47.5 mg/dL, 101.6±35.4 mg/dlL, 155.8±18.6 mg/dL, and 47.0±2.3 mg/dL, respectively, giving percentage changes of -17.6% (p 0.05, and -2.1% (p>0.05, respectively. Following the 4 weeks of treatment, the levels of IL-6 and hs CRP were 6.955±5.555 pg/mL, and 0.753±0.571 mg/dL, respectively, giving percentage changes of 51.8 (p>0.05, and 36.5% (p>0.05, respectively. There was no significant correlation between the level of LDL-cholesterol and the levels of IL-6, or hs CRP at the baseline, or post-treatment. There was also no significant correlation between the change of LDL-cholesterol and the changes of IL-6 or hs CRP levels during the simvastatin therapy. There was no significant correlation between the levels of IL-6 and hs CRP at the baseline or ost-treatment. Conclusion：Our data showed that in patients with unstable

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively.

Effect of statins on bone mineral density and bone histomorphometry in rodents.

Statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1, 5, 10, and 20 mg. kg(-1). d(-1)), atorvastatin (2.5 mg. kg(-1). d(-1)), and pravastatin (10 mg. kg(-1). d(-1)) administered orally for 12 weeks to intact female Sprague-Dawley rats and the effect of 20 mg. kg(-1). d(-1) simvastatin in sham-operated and ovariectomized rats on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH) and compared them with controls. BMD was decreased by 1 mg. kg(-1). d(-1) simvastatin (P=0.042), atorvastatin (P=0.0002), and pravastatin (P=0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA, P=0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by 20 mg. kg(-1). d(-1) simvastatin in 2 separate groups of intact rats and were reflected by a relatively unchanged BMD. At lower doses, 1 mg. kg(-1). d(-1) simvastatin decreased bone formation while increasing bone resorption, as reflected by a marked decrease in BMD. Ovariectomized animals receiving 20 mg. kg(-1). d(-1) simvastatin showed no change in BMD relative to the untreated, ovariectomized controls; their increase in bone formation was smaller than in sham-operated rats receiving simvastatin, and there was no change in bone resorption. Dose-response curves of simvastatin for bone formation and resorption differed. These studies indicate that (1) statins decrease BMD in rodents, (2) high-dose simvastatin increases bone formation and resorption, (3) low-dose simvastatin decreases bone formation and increases bone resorption, (4) the effects of simvastatin on QBH differ at different dosages, (5) the effects of simvastatin seen in intact rats are not observed in ovariectomized rats, and (6) simvastatin is unable to prevent bone loss caused by ovariectomy.

Influence of low dose aspirin and simvastatin on blood pressure, flow-dependent vasodilatation, tonus and elasticity of brachial artery in hypertensive nonhyperlipidemic subjects

Influence of low dose aspirin and simvastatin on blood pressure, flow-dependent vasodilatation, tonus and elasticity of brachial artery in hypertensive nonhyperlipidemic subjects

Simvastatin attenuates vascular hypercoagulability in cardiac transplant recipients.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to reduce cardiac allograft failure and to lower the incidence of transplant coronary artery disease. These effects result from as yet unknown mechanisms not clearly attributable to lipid lowering. We here report that low-dose simvastatin treatment inhibits excessive expression of monocyte tissue factor (TF) and reduces the persistent hypercoagulability state seen in cardiac transplant recipients. Fifteen consecutive heart transplant recipients receiving standard oral immunosuppression were newly assigned to a 10 mg daily simvastatin therapy. Levels of TF activity in both unstimulated and lipopolysaccharide-stimulated peripheral blood mononuclear cells drawn from transplant recipients before and under simvastatin therapy were evaluated by one-stage clotting assay. Monocyte TF activity was found to be significantly increased in cardiac transplant recipients when compared with healthy controls. Excessive monocyte procoagulant activity was reduced in cardiac transplant recipients during simvastatin treatment. This effect occurred independently of the reduction of serum low-density lipoprotein cholesterol. As demonstrated by reverse transcriptase-polymerase chain reaction, monocyte TF reduction by simvastatin, observed in 13 of the 15 transplant recipients investigated, could be ascribed to an inhibition of monocyte TF gene transcription. The reduction of monocyte TF activity during treatment with simvastatin paralleled with the normalization of elevated levels of thrombin-antithrombin complex, prothrombin fragment F1+2, and D-dimer, which are markers of thrombin and fibrin formation indicating coagulation activation after cardiac transplantation. Inhibition of monocyte TF expression and attenuation of the persistent hypercoagulable state observed in cardiac transplant recipients during treatment with simvastatin may represent an important mechanism by which HMG-CoA reductase inhibitors protect against the development of transplant coronary artery disease.

Micronized fenofibrate: a new fibric acid hypolipidemic agent.

To review the efficacy and safety of fenofibrate in the management of hyperlipidemias. A MEDLINE search (1974-October 1998), Current Contents search, additional references from article bibliographies, and the package insert from the manufacturer were used to identify data for evaluation. Studies evaluating fenofibrate (peer-reviewed publications, package insert data) were considered for inclusion. Abstracts and data on file with the manufacturer were not considered for inclusion. English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, clinical use, and tolerability of fenofibrate. Data from animals and in vitro systems were included only when necessary to explain the drug's pharmacology. Micronized fenofibrate is a fibric acid derivative approved by the Food and Drug Administration (FDA) in February 1998 for the treatment of types IV and V hyperlipidemia. Data from the peer-reviewed literature also support the use of fenofibrate in types IIa, IIb, and III hyperlipidemias. Micronized fenofibrate 67-201 mg/d is useful as monotherapy or as an adjunct to other hypolipidemics and dietary therapy. In placebo-controlled clinical trials, regular formulation fenofibrate 300-400 mg/d lowered serum triglyceride (TG) concentrations by 24-55%, total cholesterol by 9-25%, low-density lipoprotein cholesterol (LDL-C) concentrations by 6-35%, and raised high-density lipoprotein cholesterol (HDL-C) concentrations by 8-38%. Few comparative data exist regarding fenofibrate versus clofibrate and gemfibrozil. In noncomparative and comparative clinical trials, fenofibrate appeared to be well tolerated. The most common causally related adverse events were digestive, musculoskeletal, and dermatologic in nature. Concurrent use of fenofibrate and a hydroxymethylglutaryl-coenzyme A inhibitor may increase the risk of myopathy and/or rhabdomyolysis, although recent data suggest that concurrent use of fenofibrate with low-dose simvastatin or pravastatin is safe. Fenofibrate may enhance the effect of oral anticoagulants. Fenofibrate reduces serum TG, total cholesterol, and LDL-C, and raises HDL-C to clinically relevant degrees. Its spectrum of activity appears to exceed that recommended for types IV and V hyperlipidemia to encompass types IIa, IIb, and III hyperlipidemias as well. To this extent, it may be considered a broader-spectrum fibrate than is indicated by its FDA approval. Adverse effects of fenofibrate appear to be similar to those of other fibrates and require routine monitoring (clinical, liver function). Long-term safety data are readily available from drug registries in many countries where the product has been available for nearly two decades. Cost-effectiveness studies comparing fenofibrate with other hypolipidemics demonstrate benefits of fenofibrate over simvastatin in types IIa and IIb hyperlipidemia. The need for dosage titration of the micronized preparation from 67 mg/d upward to a final dose of 200 mg/d is also not supported by peer-reviewed literature (except in the case of renal impairment). Although preliminary data on plaque regression are encouraging, published clinical studies evaluating the impact of fenofibrate on cardiovascular morbidity and mortality are awaited. Micronized fenofibrate is worthy of formulary inclusion.

F033 Is low dose simvastatin effective to lower cholesterol in coronary patients?

F033 Is low dose simvastatin effective to lower cholesterol in coronary patients?

Long-Term Efficacy and Safety of Fenofibrate and a Statin in the Treatment of Combined Hyperlipidemia

To assess the long-term efficacy and use of fenofibrate together with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (“statin”) in the treatment of elevated levels of triglycerides and low-density lipoprotein (LDL) cholesterol, we conducted a study that compared a before- and after-case series. The study involved 80 patients with a diagnosis of combined hyperlipidemia and existing coronary artery disease (81% of patients) or outpatients with ≥3 risk factors for coronary artery disease who had been receiving treatment at a tertiary care center. Fasting biochemical measures were obtained at baseline during monotherapy with a statin consisting of pravastatin 20 mg once daily or simvastatin 10 mg once daily (39 patients) or fenofibrate 300 mg once daily (41 patients), and during a 2-year period of combination therapy. This combination therapy comprised fenofibrate 300 mg once daily or micronized fenofibrate 200 mg once daily taken together with pravastatin 20 mg once daily (63 patients) or simvastatin 10 mg once daily (17 patients). The main outcome measures were: (1) absolute and percent change in total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol; (2) percentage of patients with alanine aminotransferase ≥2× the upper limits of normal on any occasion; (3) percentage of patients with creatinine kinase ≥3 times the upper limits of normal on any occasion; (4) absolute changes in alanine aminotransferase and creatinine phosphokinase; and (5) months on combination therapy. Patients receiving combination therapy had a mean total cholesterol (± standard error of the mean [SEM]) that was significantly decreased by 26 ± 1%, triglycerides by 41 ± 3%, and LDL cholesterol by 28 ± 2%, and mean HDL cholesterol that was significantly increased by 22 ± 6%. These changes correspond to mean absolute changes of total cholesterol: −75 ± 5 mg/dL; triglycerides: −94 ± 13 mg/dL; LDL cholesterol: −52 ± 5 mg/dL; and HDL cholesterol: 5 ± 1 mg/dL. During combination treatment, alanine aminotransferase increased by 2 ± 2 U/liter (not significant) and creatinine phosphokinase decreased by 4 ± 13 U/liter (not significant). During treatment, 8 patients (10%) had transitory isolated elevations in alanine aminotransferase levels ≥2 times the upper limits of normal and 2 patients (2.5%) had an isolated and transitory elevation of creatinine kinase (≥3× but <6× upper limits of normal) without associated muscle symptoms. Patient-years on combination therapy equaled 220.6 (average 2.06 years per patient). The results demonstrated that combination treatment with fenofibrate and low-dose simvastatin or pravastatin is generally safe and effective for the treatment of combined hyperlipidemia in patients with normal hepatic and renal function.

Low-Dose Simvastatin in the Treatment of Mild to Moderate Hypercholesterolaemia

HMG CoA reductase inhibitors have been shown to be effective agents in lowering cholesterol in patients with primary hypercholesterolaemia. The aim of this study was to determine whether simvastatin at a low dose of 5mg given once in the evening was also effective in lowering cholesterol. In a multicentre, randomised, placebo-controlled study, 86 subjects (64 males, 22 females) with a mean age of 61 ± 13.1 years and serum total cholesterol concentrations of 5.2 to 7.0 mmol/L were investigated. After an initial 10 weeks of a standard lipid-lowering diet, the last 4 weeks on placebo, participants were randomised to receive either simvastatin 5mg or matching placebo to be taken in the evening. After 6 weeks, study participants not achieving a target cholesterol of ≤ 5.2 mmol/L were titrated to simvastatin 10mg or matching placebo for a further 6 weeks. At 6 weeks, 77% of the simvastatin-treated group had achieved a cholesterol level of ≤ 5.2 mmol/L compared with only 5% of the placebo-treated group (p < 0.01). Simvastatin 5mg decreased total cholesterol by 17.7%, low-density lipoprotein cholesterol by 25.4% and triglyceride by 5.8%; high-density lipoprotein cholesterol rose by 8.7%. Increasing simvastatin to 10mg in 23% of subjects did not significantly alter the lipid levels. Clinical and biochemical adverse experiences were few and were similar in the simvastatin and placebo groups. This study demonstrated that simvastatin at a low dose of 5mg is a well tolerated and effective lipid-lowering agent in subjects with mild to moderate hypercholesterolaemia.

Effects of low-dose simvastatin therapy on serum lipid levels in patients with moderate hypercholesterolemia: a 12-month study

The aim of this study was to investigate the safety and long-term effects on serum lipid levels of low-dose simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in Japanese patients with moderate primary hypercholesterolemia. We assigned 201 patients (68 men and 133 women; mean ± SD age, 61.3 ± 10.2 years) with serum total cholesterol levels ≥220 mg/dL to receive simvastatin 5 mg each evening; the treatment period was 1 year. Serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol levels decreased significantly in response to simvastatin therapy, and the changes were maintained throughout the treatment period. Mean total cholesterol decreased from 269.9 ± 35.4 mg/dL to 215.2 ± 34.5 mg/dL (20.3%), triglycerides decreased from 183.0 ± 110.2 mg/dL to 155.5 ± 88.5 mg/dL (15.0%), and LDL cholesterol decreased from 180.0 ± 33.1 mg/dL to 130.1 ± 35.1 mg/dL (27.7%). Total cholesterol, triglycerides, and LDL cholesterol tended to decline when the pretreatment values were higher; the critical values and the bidirectional changes of the serum lipid levels were 188.1, 109.5, and 91.6 mg/dL, respectively. Although the serum level of high-density lipoprotein cholesterol did not change significantly, it tended to increase more when the pretreatment values were lower; the “critical value” was 70 mg/dL. Nine patients experienced mild adverse events, but none discontinued simvastatin during the 12-month treatment period. We found that low-dose simvastatin therapy is effective in achieving long-term decreases in serum lipid levels and is well tolerated by patients with moderate hypercholesterolemia. Simvastatin therapy may result in normalization of serum lipid levels.

Simvastatin further enhances the hypocholesterolemic effect of soy protein in rabbits.

The effects of three dietary proteins (casein, cod, soy) and low dose simvastatin, an inhibitor of hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, on serum lipids were investigated.New Zealand rabbits were fed purified diet (20% protein, 11% fat and 0.06% cholesterol) for 28 days. Animals received either 1.4 mg simvastatin or placebo orally during the last 14 days. A randomized 3 × 2 factorial design was used for the administration of diet and drug treatments.Mean food intake and body weight of the animals in all groups were similar. In placebo groups, soy protein decreased (p = 0.06) total cholesterolemia with significantly (p = 0.009) lower high-density lipoprotein (HDL) cholesterol, and significantly (p = 0.004) higher very low-density lipoprotein (VLDL) triglycerides (TG), compared to animal proteins. Addition of low dose simvastatin to soy protein induced a further decrease of serum total cholesterol, decreased VLDL and low-density lipoprotein (LDL) cholesterol, and LDL (apolipoprotein B), as well as improved VLDL-TG and HDL cholesterol levels. No similar reduction was seen when simvastatin was combined with casein or cod protein.These results show that low dose simvastatin may enhance the hypocholesterolemic effect of soy protein compared to animal proteins in the rabbit.

Efficacy and Tolerability of Low-dose Simvastatin and Niacin, Alone and in Combination, in Patients With Combined Hyperlipidemia: A Prospective Trial

BACKGROUND: Combination lipid-lowering therapy may be desirable in patients with elevated low-density lipoprotein cholesterol, high triglycerides, and low high-density lipoprotein cholesterol. This study was conducted to determine the lipid-lowering efficacy of the combination of low-dose simvastatin and niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol. METHODS AND RESULTS: In this multicenter, prospective, randomized trial, 180 patients with hypercholesterolemia and hypertriglyceridemia and/or low high-density lipoprotein cholesterol were randomized to combination simvastatin (10 mg/day) and niacin (0.75 g/day) or to either drug alone for 9 weeks. The dose of niacin was doubled (from 0.75 g/day to 1.5 g/day) in both the combination and niacin arms for the remaining 8 weeks. The combination of simvastatin, 10 mg/day, and niacin, 1.5 g/day, reduced total, low-density lipoprotein, and very low-density lipoprotein cholesterol and triglycerides by 24%, 29%, 45%, and 31%, respectively, while increasing high-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol-lowering effect of simvastatin; however, the combination was more effective than either monotherapy at raising high-density lipoprotein cholesterol and lowering very low-density lipoprotein cholesterol (P <.05). More patients discontinued treatment because of an adverse event in the niacin (P <.03) and combination groups (P =.06) than the simvastatin group. CONCLUSIONS: Treatment of patients with combined hyperlipidemia and/or low high-density lipoprotein with combination low-dose simvastatin and niacin resulted in large reductions in total, low-density lipoprotein, and very low-density lipoprotein cholesterol and increases in HDL cholesterol. Although the combination was well tolerated in the current trial, its safety needs to be evaluated in larger trials of longer duration.

A Comparison of the Tolerability and Efficacy of Lovastatin 20 mg and Fluvastatin 20 mg in the Treatment of Primary Hypercholesterolemia.

BACKGROUND: To compare the cholesterol-lowering potency of fluvastatin and lovastatin, a randomized, prospective, open-label parallel study was conducted in patients eligible for drug therapy by National Cholesterol Education Program guidelines. The study was conducted at eight centers in the United States. METHODS AND RESULTS: Patients were required to follow a cholesterol-lowering diet and were withdrawn from all lipid-lowering agents for 4 seeks prior to study entry. Patients were randomized to receive lovastatin 20 mg of fluvastatin 20 mg daily for 6 weeks. The two treatment groups were comparable with respect to demographic and clinical characteristics. Baseline lipid levels in the two groups were comparable. Lovastatin was significantly more effective than fluvastatin in lowering total cholesterol (-;19.5% vs -12.8%, P <.001) and low-density lipoprotein cholesterol (-27.6% vs -18.2%, P <.001). Changes in high-density lipoprotein and triglyceride levels were comparable in the two groups. The differences in cholesterol lowering were similar in the three strata of coronary heart disease risk factor status as defined by the second NCEP Adult Treatment Panel. Both treatments were well tolerated. CONCLUSIONS: Across the three chronic heart disease risk strata, lovastatin appears to be significantly more potent than fluvastatin, on a per milligram basis, in lowering cholesterol levels.

Effect of low-dose simvastatin on cholesterol levels, oxidative susceptibility, and antioxidant levels of low-density lipoproteins in patients with hypercholesterolemia: a pilot study

In this pilot study, 12 patients (6 men, 6 postmenopausal women) with hypercholesterolemia were treated with low-dose (5 mg/d) simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, for 4 weeks. Low-density lipoprotein (LDL) samples were isolated at the beginning (week 0) and at the end (week 4) of the treatment regimen. Simvastatin caused significant decreases of total cholesterol (−18.1%), LDL cholesterol (−27.6%), and apolipoprotein B (−21.8%), and significantly reduced total cholesterol, free cholesterol, cholesterol esters, phospholipids, and protein in LDL without significantly changing the component ratios and fatty acid levels of LDL. However, simvastatin therapy had no major effects on either antioxidant levels in LDL or the oxidative susceptibility of LDL. We conclude that low-dose simvastatin significantly reduces LDL cholesterol levels without increasing the oxidative susceptibility of LDL or decreasing the antioxidant levels of LDL, and thus may reduce the risk of coronary artery disease.

Efficacy of low doses of simvastatin and niacin used concomitantly in patients with combined hyperlipidemia

Efficacy of low doses of simvastatin and niacin used concomitantly in patients with combined hyperlipidemia

Efficacy analysis by age of low-dose simvastatin in 3032 patients with primary hypercholesterolemia: The Belgian General Practitioner's Study

Efficacy analysis by age of low-dose simvastatin in 3032 patients with primary hypercholesterolemia: The Belgian General Practitioner's Study

Sequential fibrate and low-dose simvastatin treatment in 6422 patients with severe hypercholesterolemia: The Belgian General Practitioner's Study

Sequential fibrate and low-dose simvastatin treatment in 6422 patients with severe hypercholesterolemia: The Belgian General Practitioner's Study

SAFETY AND EFFICACY OF LOW DOSE SIMVASTATIN IN CARDIAC TRANSPLANT RECIPIENTS TREATED WITH CYCLOSPORINE

Hyperlipidemia is common in heart transplant patients. Lipid-lowering therapy poses special problems, yet may be important because accelerated graft atherosclerosis is the major factor limiting long-term survival. Simvastatin 5 mg/day was started > 6 months after surgery in 26 consecutive cardiac transplant recipients with a total serum cholesterol level of > 250 mg/dl. The dose of simvastatin was increased in 5-mg increments until total serum cholesterol fell below 220 mg/dl or until side effects developed or up to a maximal dose of 20 mg/day. The final average daily dose was 10 mg. Changes in serum lipid levels after 6 months of therapy were compared with data from a matched and concurrent control group of heart transplant patients not taking simvastatin. Immunosuppression for both groups consisted of CsA, AZA, and corticosteroids. In the simvastatin-treated group, the serum level of total cholesterol decreased by 27% from 315 +/- 53 to 230 +/- 38 mg/dl (P < 0.0001), low density lipoprotein cholesterol decreased by 40% from 205 +/- 30 to 123 +/- 32 mg/dl (P < 0.0001), and triglycerides decreased by 21% from 177 +/- 89 to 140 +/- 49 mg/dl (P < 0.01). There was no significant change in high density lipoprotein cholesterol level. Body weight and CsA blood levels remained stable. Steroid intake decreased during the study period to a similar extent in both the treated and the control groups. In the control group, no significant changes in serum lipid levels were observed. Two patients experienced a mild form of myotoxicity. In one other patient simvastatin treatment was stopped after an acute pancreatitis of uncertain etiology developed. Low dose simvastatin effectively lowers total serum cholesterol, low density lipoprotein cholesterol, and triglycerides in heart transplant patients. With due precautions, the safety profile of the drug in this patient population seems reasonable.

Low-dose (5 mg) simvastatin versus gemfibrozil in the treatment of primary moderate hypercholesterolemia: Results of a belgian multicenter study

A multicenter Belgian study was conducted to compare the safety, tolerability, and effectiveness of simvastatin 5 mg/day and gemfibrozil 1200 mg/day in patients with primary moderate hypercholesterolemia. Thirty-one investigators in 30 sites participated in this study consisting of a 4-week washout period followed by a 6-week open-label treatment period. One hundred ninety-nine patients (144 with type IIa hyperlipidemia [triglycerides ⩽200 mg/dl] and 55 with type IIb hyperlipidemia [triglycerides >200 mg/dl]) were evaluated. Patients were eligible for inclusion if their total cholesterol was ⩾250 mg/dl and ⩽300 mg/dl after the washout period. The evaluation of efficacy was based on percentage changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, LDL-C/HDL-C ratio, and total triglycerides. Clinical safety was assessed by evaluating the rate of spontaneous adverse experiences and by measuring blood pressure, pulse rate, and body weight. Adverse laboratory values were also evaluated. The mean percent changes from baseline at week 6 were −17.8% in the simvastatin group versus −10.5% in the gemfibrozil group ( P < 0.01) for total cholesterol, −26% in the simvastatin group versus −11.8% in the gemfibrozil group ( P < 0.01) for LDL-C, +10.2% in the simvastatin group versus +16.2% in the gemfibrozil group (not significant [NS]) for HDL-C, and −13.9% in the simvastatin group versus −32% in the gemfibrozil group ( P < 0.01) for total triglycerides. Simvastatin 5 mg reduced TC, LDL-C, the LDL-C/HDL-C ratio, and the TC/HDL-C ratio more than gemfibrozil. The effect of gemfibrozil on total triglycerides and on HDL-C was larger than that of simvastatin 5 mg. No firm conclusions could be drawn from subgroup analyses because of the limited sample size. Both drugs were well tolerated. The treatment groups were similar with respect to the proportion of patients with clinical and laboratory adverse experiences (11 in the simvastatin group versus 17 in the gemfibrozil group—NS). Due to the efficacy and lack of side effects of simvastatin, the use of simvastatin at a starting dose of 5 mg/day can be recommended in a majority of patients with moderate hypercholesterolemia if diet modification has proved to be ineffective.

Low-Dose Simvastatin Is a Well-Tolerated and Efficacious Cholesterol-Lowering Agent in Ciclosporin-Treated Kidney Transplant Recipients: Double-Blind, Randomized, Placebo-Controlled Study in 40 Patients

The high prevalence of hypercholesterolemia in kidney transplant recipients probably contributes to the high cardiovascular mortality in these patients. Except for diet, there is no generally recommended cholesterol-lowering treatment. We conducted a double-blind, randomized, placebo-controlled study with low-dose simvastatin in 40 ciclosporin (CS)-treated kidney transplant recipients during 16 weeks, focusing on side effects and dose finding. In the simvastatin group, the mean serum total and LDL cholesterol concentrations decreased by 23 and 33%, respectively, and the mean serum HDL cholesterol concentration increased by 12%, after 4 weeks of treatment with simvastatin 10 mg daily. Increasing the dose to 20 mg daily in a few patients only resulted in marginal further reductions of the serum cholesterol concentrations at the expense of doubling the plasma simvastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity concentrations. The differences between the changes in the serum cholesterol concentrations in the simvastatin group and the negligible changes in the placebo group were statistically significant. There was no case of proximal myopathy and the serum creatine kinase concentrations did not differ between treatment groups. In conclusion, low-dose simvastatin appears to be a well tolerated and efficacious cholesterol-lowering treatment in CS-treated kidney transplant recipients. Simvastatin 10 mg daily seems to be the most suitable dose for the majority of these patients.