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PubMed2002

Comparison of the efficacy and safety of pravastatin and simvastatin in heart transplantation.

AIMS: Data on the safety and efficacy of HMG CoA reductase inhibitors in managing dyslipidemia in heart transplant recipients is inadequate. We undertook this study to evaluate the comparative safety and efficacy of simvastatin and pravastatin in lowering lipids in heart transplant recipients. METHODOLOGY: Forty eight patients (38 males) who received heart transplantation between 1995 and 1997, and who had no contraindications to statin therapy or history of myopathy were randomized to receive either pravastatin (n=24) or simvastatin (n=24) for six months. Detailed fasting lipid profiles, hepatic function tests, and serum creatinine phosphokinase were obtained regularly. Baseline and six month characteristics were compared using the unpaired student t test for continuous variables and Chi-square analysis or Fisher's exact test, as appropriate. RESULTS: Baseline total cholesterol levels, LDL cholesterol levels, HDL cholesterol levels, and triglyceride levels were similar in the two groups. At six months, the total cholesterol, LDL cholesterol, and triglyceride levels were greatly reduced in both groups, with greater reductions in the simvastatin group than in the pravastatin group. Only modest increases were noted in HDL cholesterol levels in the two groups. No significant adverse effects were noted, and no complications with drug withdrawals occurred. Patient compliance exceeded 97%. CONCLUSION: Simvastatin and pravastatin are safe and very effective in total cholesterol and LDL cholesterol lowering in heart transplant recipients, with simvastatin being more efficacious than pravastatin in lipid lowering in this group of patients.

Adult↗
PubMed2002

[Simvastatin and extrinsic coagulation pathway in peritoneally dialyzed patients].

Peritoneally dialyzed subjects (CAPD) are prone to dyslipidemia and have a high risk of cardiovascular death. Statins (hydroxy-methylglutaryloCoA reductase inhibitors) show beneficial effects on serum lipids and hemostasis in kidney diseases. The purpose of this study was to assess platelet functions, some hemostatic parameters-extrinsic coagulation pathway-total, truncated, free TFPI (tissue factor pathway inhibitor), TF (tissue factor), TFPI/Xa and TF/VIIa complexes, as well as a marker of endothelial cell injury--von Willebrand factor--vWF and serum lipids in 10 hyperlipidemic CAPD patients treated with simvastatin (Zocor, MSD, at a dose of 10 mg at bedtime) for 3 months. Cholesterol and LDL fell significantly as early as after 1 month and remained lowered during further months of the therapy. No significant changes in von Willebrand factor, free TFPI, TF, TFPI/Xa and TF/VIIa complexes were found during therapy with simvastatin. Truncated TFPI decreased significantly as early as after 1 month and total TFPI decreased after 3 months of the therapy with simvastatin. Simvastatin is an effective hypolipemic agent. It seems that simvastatin have no or only little effect on endothelial function and extrinsic coagulation pathway in peritoneally dialyzed patients.

Adult↗
PubMed2003

[Simvastatin-induced lichen planus pemphigoides].

INTRODUCTION: Simvastatin is a competitive inhibitor of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase which is effective in the treatment of various hyperlipidemia. We report a case of lichen planus pemphigoides induced by simvastatin treatment. CASE REPORT: A 63-year-old man was treated for two months with simvastatin for hypercholesterolemia. One month later he developed a pruriginous and bullous lichenoid eruption. Histological and direct immunofluorescent features were consistent with the diagnosis of lichen planus pemphigoides. The Western blot analysis revealed antibodies directed against BP 180 kDa antigens. All the lesions progressively disappeared after treatment was discontinued. DISCUSSION: Lichen planus pemphigoides may be due to the intake of drugs such as cinnarizine, captopril, ramipril and furosemide. Simvastatin may induce various drug eruptions such as pruritus, eczematous rash, cheilitis, angio-oedema and urticaria, porphyria cutanea tarda, lupus-like syndrome, dermatomyositis and lichenoid eruption. With the increasing use of HMG-CoA reductase inhibitors, an association between simvastatin and lichen planus pemphigoides should be kept in mind.

Blotting, Western↗
PubMed2003

Simvastatin reduces infarct size in a model of acute myocardial ischemia and reperfusion in the rat.

BACKGROUND: This study was designed to investigate the effects of simvastatin in a rat model of acute myocardial infarction. MATERIAL/METHODS: Male Wistar rats were anesthetized (thiopentone sodium 120 mg/kg). After a thoracotomy, the left-anterior-descending coronary artery (LAD) was occluded (for 25 min) and reperfused (for 120 min). Area at risk (AR) was determined with Evans Blue dye and infarct size after staining of the area at risk with nitroblue tetrazolium. RESULTS: In rats, which received the vehicle for simvastatin (10% DMSO, 1 ml/kg i.v. at 1 h prior to the occlusion of the LAD), occlusion of the LAD for 25 min followed by reperfusion for 2 hours resulted in an infarct size of 54 +/- 4% (n=7) of the AR. When compared with vehicle, administration of simvastatin (1 mg/kg i.v. bolus administration at 1 h prior to the onset of myocardial ischemia) caused a significant reduction in myocardial infarct size of 39%. LAD-occlusion and reperfusion caused a progressive fall in mean arterial blood pressure (when compared with sham-operated animals). Simvastatin had no significant effect on blood pressure. CONCLUSIONS: The result indicates that simvastatin, an inhibitor of HMG-CoA reductase and a ligand of PPAR-a and PPAR-g, reduces the tissue necrosis associated with acute myocardial infarction. We propose that statins may be useful in conditions associated with ischemia-reperfusion of the heart and other organs.

Animals↗
PubMed2003

Lipid-lowering efficacy and safety of varying doses of Simvastatin in patients with early stage acute coronary syndromes: one-year follow-up study.

OBJECTIVE: To investigate whether patients, who are at risk of major acute coronary events, are safe to undergo and benefit from early intervention after using simvastatin. METHODS: The study was a randomized, open, two-dosage-controlled trial to evaluate the safety and benefits of simvastatin administered to 197 patients (10 mg group, n = 98 and 20 mg group, n = 99), within 48 hours of hospitalization for a diagnosis of unstable angina or acute myocardial infarction (MI), with total cholesterol (TC) >/= 180 mg/dL or low-density lipoprotein cholesterol (LDL-C) >/= 100 mg/dL. Lipid levels were measured immediately, followed by the 3rd, 6th and 12th month after admission and all adverse events were recorded during follow-up. RESULTS: TC levels fell by 10.15% and 14.52% in the 10 mg and 20 mg groups (P < 0.05), and LDL-C levels fell 13.87% and 19.38% in the 10 mg and 20 mg groups, respectively (P < 0.01), 12 months after using simvastatin. The rates of achieving target TC reached 26.3% and 36.5% in the 10 mg and 20 mg groups (P < 0.01), and that of LDL-C reached 28.2% and 40.3% in the 10 mg and 20 mg groups, respectively (P < 0.01). There were higher rates of MI and re-hospitalization resulting from angina pectoris and revascularization in the 10 mg group compared with the 20 mg group. CONCLUSIONS: The results suggest that early intervention with the HMG-CoA reductase inhibitor, simvastatin, in acute coronary syndromes is possible and safe. It also indicates that the clinical dosage of simvastatin are relatively smaller than that for satisfactory lipid control in patients with acute coronary syndromes.

Acute Disease↗
PubMed1992

[Mid-term clinical study of the effectiveness of and tolerability to simvastatin ++ in dyslipidemic patients].

The HGM-CoA reductase inhibitors, blaking up intracellular synthesis of cholesterol, support the receptorial captation of cholesterol with a reduction in plasma levels. The simvastatin efficacy was evaluated in 12 patients, mean age 59 +/- 10 years with a primary hypercholesterolemia. All the patients were on a pharmacologic wash out for at least 6 weeks and dietetic treatment (according to their weight and daily needs) for a week. Total cholesterol, HDL-cholesterol and triglycerides plasma levels were taken at time 0. Then a treatment with simvastatin 10 mg/die was begin for 4 weeks and than increased to 20 mg in patients with plasma cholesterol > 200 mg/100 ml at the end of fourth week. In some patients the dose was increased up to 40 mg for the elevated levels of plasma cholesterol at the end of the second month. All the parameters above were controlled monthly for three months. A control was performed at the end of sixth month of treatment. After 4 weeks treatment, simvastatin induced reduction in cholesterol plasma levels (p < 0.005), that continued during the whole time treatment (228 mg/dl at 24 week, p < 0.005 vs basal). The mean dosage of the simvastatin at fourth month was of 25 mg/die. During the treatment an increase of HDL plasma levels was noted, but this increment wasn't statistical significant (40 +/- 7 vs 45 +/- 9 mg/100 ml). No significant impairment of principal metabolic and laboratory parameters were observed during the treatment. These data indicate that simvastatin in small dose induce a reduction in cholesterol plasma levels with a significant increase in HDL without side effects.

Adult↗
PubMed1992

Beneficial effect of simvastatin in patients with drug resistant familial hypercholesterolaemia.

AIMS: To investigate the effects of simvastatin in patients with heterozygous familial hypercholesterolaemia refractory or intolerant to routine drug therapy. METHOD: Eighteen patients were given increasing doses of 10, 20 and 40 mg simvastatin for eight week periods, followed by a control period on their former drug therapy in a prospective, crossover clinical study. RESULTS: Mean total and low density lipoprotein cholesterol (SEM) were significantly lower on 40 mg simvastatin alone than at the end of the control period (7.3 (0.3) mmol/L vs 10.7 (0.4) and 5.1 (0.3) vs 7.8 (0.5) respectively; p less than 0.01). Apo-B was also significantly lower on 40 mg simvastatin (p less than 0.01). CONCLUSION: Simvastatin offers effective cholesterol lowering for patients with drug resistant familial hypercholesterolaemia.

Adult↗
PubMed2004

Effects of an HMG-CoA reductase inhibitor, simvastatin, on human myeloma cells.

To look for new candidates for agents to use in maintenance therapy for myeloma patients, the growth inhibitory effects of a 3-hydroxy-3-mehtylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin), simvastatin, was analyzed using human myeloma cell lines. Several investigations have indicated growth reduction in certain lineages of cancer cells including one report on myeloma, and inhibitory effects of statins on GTPases and involving MAP-kinases. Most (12 out of 13) myeloma lines examined showed growth inhibition when cultured with various concentrations (1-30 microM) of simvastatin in a dose-dependent manner. Simvastatin in combination with other biological response modifiers such as ATRA or DEX had additional effects on growth. In addition, anti-oxides prevented the simvastatin-induced growth inhibition and apoptosis. Furthermore, myeloma cells treated with simvastatin clearly showed inactivation of various MAP-kinase pathways such as ERK1/2, MEK1/2, JNK, and p38. Based on these findings, statins may be suitable for clinical usage in maintenance therapy for myeloma patients.

Antioxidants↗
PubMed2004

Effect of simvastatin on endothelium-dependent vaso-relaxation and endogenous nitric oxide synthase inhibitor.

AIM: To investigate the effect of simvastatin on endothelium-dependent vasorelaxation and endogenous nitric oxide synthesis inhibitor asymmetric dimethylarginine (ADMA) in rats and cultured ECV304 cells. METHODS: Endothelial injury was induced by a single injection of low density lipoprotein (LDL) (4 mg/kg, 48 h) in rats or incubation with LDL (300 mg/L) or oxidative-modified LDL (100 mg/L) in cultured ECV304 cells, and vasodilator responses to acetylcholine (ACh) in the aortic rings and the level of ADMA, nitrite/nitrate (NO) and tumor necrosis factor-alpha (TNF-alpha) in the serum or cultured medium were determined. And the adhesion of the monocytes to endothelial cells and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in the cultured ECV304 cells were measured. RESULTS: A single injection of LDL decreased endothelium-dependent relaxation to ACh, markedly increased the serum level of endogenous ADMA and TNF-alpha, and reduced serum level of NO. Pretreatment with simvastatin (30 or 60 mg/kg) markedly attenuated inhibition of vasodilator responses to ACh, the increased level of TNF-alpha and the decreased level of NO by LDL, but no effect on serum concentration of endogenous ADMA. In cultured ECV304 cells, LDL or ox-LDL markedly increased the level of ADMA and TNF-alpha and potentiated the adhesion of monocytes to endothelial cells, concomitantly with a significantly decrease in the activity of DDAH and serum level of NO. Pretreatment with simvastatin (0.1, 0.5, or 2.5 micromol/L) markedly decreased the level of TNF-alpha and the adhesion of monocytes to endothelial cells, but did not affect the concentration of endogenous ADMA and the activity of DDAH. CONCLUSION: Simvastatin protect the vascular endothelium against the damages induced by LDL or ox-LDL in rats or cultured ECV304 cells, and the beneficial effects of simvastatin may be related to the reduction of inflammatory cytokine TNF-alpha level.

Animals↗
PubMed2002

The effect of Simvastatin upon serum pseudocholinesterase and plasmatic factor VII.

UNLABELLED: The statins have a moderate lowering effect upon triglycerides, one hypothesis suggesting an inhibitory effect upon liver VLDL synthesis. Because VLDL synthesis is related to other hepatic protein synthesis we studied the effect of Simvastatin upon serum cholinesterase activity and factor VII activity, which are also synthetized at hepatic level. METHODS: 39 patients with ischaemic heart disease, proved by coronarography and moderate hypercholesterolaemia received for two months 20 mg Simvastatin (Zocor). The value of total Co, LDLCo, HDLCo, triglycerides, serum cholinesterase activity and factor VII activity were determined before and after treatment, by standard methods. RESULTS: Triglycerides were, together with total Co, significantly lowered during the two months treatment with Simvastatin, but the values of serum cholinesterase and factor VII activity were not significantly modified. This suggests that moderate doses of Simvastatin do not depress liver protein synthesis. CONCLUSION: Simvastatin does not lower the triglycerides level through depression of liver protein syntesis, other mechanisms being probably involved.

Adult↗
PubMed2004

Reduction of myocardial ischemia with simvastatin in addition to conventional treatment in patients with chronic coronary artery disease.

BACKGROUND: Coronary artery disease is becoming more prevalent every day. We now know that controlling the risk factors for this pathology is of the utmost importance, not only to prevent the formation of atheromatous plaques (primary prevention), but also to slow its progression, or even promote regression of existing plaques (secondary prevention). There is no longer any doubt that an increase in serum cholesterol is essential for the development and progression of atherosclerosis. Therefore, lowering cholesterol levels is a key factor in controlling this disease. It has been shown that cholesterol reduction with statins is associated with a reduction in cardiovascular morbidity and mortality. It has also been demonstrated that reducing cholesterol restores peripheral and coronary vasodilation even in subjects with no angiographic evidence of the disease. OBJECTIVE: The present study aimed at assessing the effect of simvastatin in reducing myocardial ischemia in patients with chronic atherosclerotic coronary artery disease. PATIENTS AND METHODS: Twenty-five patients with stable angina and dyslipidemia undergoing clinical treatment were studied prospectively. Their lipid profile was analyzed and the diagnosis of effort-induced ischemia was confirmed by means of exercise testing. They were then randomly distributed in two groups: the simvastatin group and the placebo group. After a four- to six-month follow-up period (average of 5.72 months), they underwent new laboratory and exercise tests. RESULTS: A significant reduction in the variation of total cholesterol (p < 0.0002) and LDL-C levels (p < 0.001) was observed in the simvastatin group, compared to the placebo group. The parameters assessed during the exercise test revealed a significant improvement in ST-segment depression during effort (p < 0.046), as well as a decrease in precordial pain in the treated group during exertion, when comparing pre- and post-treatment periods. Patients receiving simvastatin also improved their functional capacity (p < 0.016), subjectively assessed by the angina pectoris classification of the Canadian Cardiovascular Society. CONCLUSIONS: These results suggest that the association of simvastatin and conventional treatment in patients with stable angina reduces effort-induced ischemia, and can be used with this group of patients, particularly those considered ineligible for invasive therapeutic intervention.

Adult↗
PubMed2005

[Efficacy and safety of combination therapy with simvastatin and fenofibrate for combined hyperlipidemia].

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of combination therapy with simvastatin and fenofibrate in patients with combined hyperlipidemia. METHODS: A total of 221 patients with combined hyperlipidemia were randomly assigned to receive 10 mg simvastatin (n = 72) or 200 mg fenofibrate (n = 68), or a combination of 10 mg simvastatin + 200 mg fenofibrate (n = 81) for 6 months. Lipid profiles, physical and laboratory investigations for adverse effects were assessed. RESULTS: (1) Combination treatment were more effective in normalizing lipid profile than any monotherapy. Serum TC, LDL-C, and TG were reduced by 30%, 37% and 56% respectively, whilst HDL-C significantly increased by 24% (all P < 0.01). The improvement in TG and HDL-C achieved by combination treatment was superior to fenofibrate or simvastatin alone. (2) The success rate of TC, LDL-C and TG control in the combination therapy group were 51%, 55% and 61% respectively, with an overall success rate (all three together) of 45%, which was superior to either drug given as monotherapy. (3) All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy. CONCLUSION: The results of this study demonstrated that combination therapy with fenofibrate (200 mg/day) and low-dose simvastatin (10 mg/day) is more effective than monotherapy in patients with combined hyperlipidemia, and is generally safe and well tolerated.

Drug Therapy, Combination↗
PubMed2005

[Effect of simvastatin on cardiac fibrosis in patients with essential hypertension].

OBJECTIVE: To explore the effect of simvastatin on myocardiac fibrosis in patients with essential hypertension (EH). METHODS: Sixty EH patients were randomly assigned into 2 groups: Benazepril (10 mg/d) group (n = 28) and simvastatin (20 mg/d) + benazepril (10 mg/d) group. Procollagen type III aminoterminal peptide (PIIIP), and procollagen type IV aminoterminal peptide (PIVP) levels in serum as well as transforming growth factor beta 1 (TGFbeta1) level in plasma were measured by radioimmunoassay (RIA) before and 6 months after the treatment. Doppler ultrasound recordings were obtained from all patients before and 6 months after the treatment to determine several parameters related to the left ventricular anatomy and function. RESULTS: After 6 month of treatment, the mean blood pressure (MBP), PIIIP, PIVP, TGFbeta1, left ventricular mass index (LVMI), interventricular spectum dimension (IVSD), and left ventricular posterio wall dimension (LPWD) in the 2 groups were significantly lower than those before the treatment. TGFbeta1 decreased in the simvastatin and benazepril group compared with the benazepril group (P < 0.01). The ratio of early diastolic blood flow velocity of mitral valve (VE) and blood flow velocity of atrium systolic period (VA) in the 2 groups significantly increased after 6 months of treatment, and the ratio in the simvastatin and benazepril group was significantly higher than that in the enazepril group (P < 0.05). CONCLUSION: Angiotension converting enzyme inhibitor combined with simvastatin is helpful to reduce the myocardial fibrosis and to improve the left ventricular hypertrophy and diastolic function in EH patients.

Adult↗
PubMed2005

[Effects of aggressive therapy with simvastatin in patients with acute coronary syndrome and initially normal level of LDLP cholesterol on cardiovascular outcomes (LAOKOON). Pilot randomized trial].

AIM: To examine anti-inflammatory effect of statins on outcomes of acute coronary syndrome (ACS). MATERIAL AND METHODS: The trial included 211 ACS patients without ST elevation at ECG. The patients were followed up for 180 days. The anti-inflammatory action was studied for 30 days. The patients were divided into two groups by the treatment: simvastatin 10 mg + aspirin 325 mg (104 patients, group 1) and simvastatin 40 mg + aspirin 325 mg (107 patients, group 2) for 30 days. RESULTS: Simvastatin in maximal dose lowed LDLP cholesterol from 101 +/- 9.8 to 72 +/- 3.3 mg/dl, in a minimal dose--from 104 +/- 11.3 to 81 +/- 2.1 mg/dl (p < 0.05). Only maximal dose simvastatin produced a significant reduction of C-reactive protein (CRP) to the disease day 14. The integral index including all cases of cardiovascular death +acute myocardial infarction+progressive angina+rehospitalization was 70 scores for group 1 and 137 for group 2 (p = 0.047). CONCLUSION: Use of simvastatin in ACS patients, initially normal level of LDLP cholesterol and elevated level of CRP produced a dose-dependent effect, alleviated inflammation and improved the disease course.

Acute Disease↗
PubMed1992

Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N,N'-bis(2-chloroethyl)-N-nitrosourea and beta-interferon on human glioma cells.

The effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on human glioma cell growth was investigated. When incubated with simvastatin, cell proliferation decreased in a concentration-dependent fashion, as measured by cell number and [3H]-thymidine incorporation into DNA (concentration producing 50% inhibition, 60 nM). The effect was detectable 12 h after cells were exposed to the drug and persisted for 2 days. Addition of mevalonate to cells exposed effect of simvastatin in combination with beta-interferon and N,N'-bis(2-chloroethyl)-N-nitrosourea, both antitumoral drugs, was also evaluated by cell growth inhibition assay. The concentration producing 50% inhibition for each of these drugs was 650 units/ml and 50 nM, respectively. Subliminal concentrations of beta-interferon or N,N'-bis(2-chloroethyl)-N-nitrosourea were incubated together with 1 nM simvastatin. The data were analyzed with the aid of an isobologram using the concept of an envelope of additivity. Simultaneous cell exposure to simvastatin with either N,N'-bis(2-chloroethyl)-N-nitrosourea or beta-interferon produced a strong synergistic inhibitory effect on cell proliferation. These data provide in vitro support for the possibility that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, utilized as plasma cholesterol-lowering agents, could potentiate the effect of antiblastic drugs on tumor growth.

Anticholesteremic Agents↗
PubMed1991

Simvastatin and side effects.

OBJECT: to investigate the symptomatic and biochemical side effect profile of simvastatin (a new cholesterol lowering drug) following routine use in a specialist hospital outpatient clinic. METHODS: all patients (n = 110) newly commenced on simvastatin at the lipid disorders clinic at the Princess Margaret Hospital in the first ten months of prescription availability were asked to complete a side effects questionnaire and biochemical evaluation at six months of therapy. RESULTS: 76.4% of patients reported experiencing no side effects with 8% of patients spontaneously reporting feeling better since commencing therapy. Nineteen point one percent of patients reported experiencing symptoms they attributed to simvastatin but had continued therapy, while a further 4.5% of patients had withdrawn from therapy because of side effects. The most frequently reported side effects were muscle ache (13.6%), and gastrointestinal symptoms (4.5%). No abnormalities in biochemical safety tests occurred. CONCLUSIONS: the rate of side effects reported with prescription use exceeds that previously encountered in clinical trials. Since simvastatin is considered effective and well tolerated it is likely to receive wide acceptance in the management of high risk hypercholesterolaemic patients. However, this study indicates the need for continued physician awareness of the main symptoms and their frequency amongst those treated with simvastatin.

Adult↗
PubMed1991

Acute cholestatic hepatitis during simvastatin administration.

Simvastatin, recently introduced in clinical practice for pharmacological treatment of hypercholesterolemia, has been found to cause minor and reversible elevations of serum transaminases. We report a case of acute cholestatic hepatitis during simvastatin therapy. Clinical, biochemical, immunological, and histological findings were consistent with a simvastatin-induced liver damage through an immunological-mediated mechanism. This case suggests a careful monitoring of liver function tests during simvastatin therapy, and caution in continuing simvastatin administration when elevations of serum transaminases take place.

Acute Disease↗
PubMed1991

[Effects and side effects of a 1-year treatment of primary hypercholesterolemia with simvastatin].

The HMG-CoA-reductase inhibitors lovastatin, pravastatin and simvastatin (statins) represent a new group of drugs for the treatment of hypercholesterolemia. The present study was performed with simvastatin, the first statin introduced in Switzerland, and involved 46 patients with primary hypercholesterolemia during one year. The dose of simvastatin was adjusted according to the serum cholesterol level; during treatment with 10, 20 and 40 mg, total cholesterol was lowered by 18, 26 and 27% respectively and LDL cholesterol by 27, 38 and 35% respectively, after one year. A combination of 40 mg simvastatin with a bile acid sequestrant or a nicotinic acid derivative resulted in a cholesterol lowering of 38% and an LDL lowering of 48% respectively. The serum triglycerides decreased only at a dose of 10 mg. The changes in LDL and HDL cholesterol were accompanied by parallel alterations in apoprotein B and A1 concentrations. Although none of the patients showed a significant increase (greater than 3 x UNL) in serum ASAT, ALAT or CK, all these values increased slightly but significantly. Tolerance of the drug was otherwise excellent; gastrointestinal side effects were only rarely reported. Therefore, simvastatin is an effective and well tolerated cholesterol-lowering drug. Whether prevention of coronary heart disease is possible, however, is not yet proven.

Anticholesteremic Agents↗