Effects of Synvinolin (Mk-733) on Plasma Lipids in Familial Hypercholesterolaemia

Mol, M.J.T.M.; Leuven, J.A. Gevers; Erkelens, D. W.; Schouten, T.A.; Stalenhoef, Anton F. H.

doi:10.1016/s0140-6736(86)90598-2

Cited by 153 publications

(60 citation statements)

References 25 publications

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“…There was a decrease in the triglyceride level and a rise in the HDL-cholesterol level, also comparable to those observed in short-term stud ies [6,7]. In patients who still had an elevated cholesterol level during monotherapy with sim vastatin, in spite of a considerable decrease in terms of percentages, the addition of a bile-acidbinding resin resulted in a further decrease in total cholesterol of 5% of the baseline value, but a less marked decrease in serum triglycerides.…”

Section: Discussionsupporting

confidence: 80%

“…The cholesterol-lowering effects especially concerned the LDL-cholesterol level, which decreased by approximately 45%. These decreases are of equal size compared to decreases observed earlier shortly after initiation of the therapy [6,7]. In spite of this considerable lipid-lowering effect of simvastatin, only 25% of the study population reached a total cholesterol level of less than 6.4 mmol/1, as a result of the very high cholesterol baseline values in these patients with heterozy gous FH.…”

Section: Discussionmentioning

confidence: 72%

“…The diagnosis of FH was based on patient and family history, lipid profile in the patient and first-degree relatives and the presence of tendon xanthomata. This group consisted of well-char acterized F H patients who had participated in earlier short-term studies [6,7]. Lipid-lowering therapy with simvastatin was started initially in all patients.…”

Section: Patientsmentioning

confidence: 99%

“…These drugs inhibit competitively 3-hydroxy-3"methylglutaryl coenzyme A (HMG-CoA) reductase, the key en zyme in the biosynthesis of cholesterol. Short-term clinical studies have shown that the cholesterol level can be reduced by means of these drugs by 30-40% on average, with a maximum reduction of 60% of the baseline value, without serious side-effects [6][7][8][9][10][11][12][13][14]. Furthermore, combination with bile-acid-binding resins can reduce serum cholesterol even further [13].…”

Section: Introductionmentioning

confidence: 99%

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Long-term experience (6 years) with simvastatin in patients with heterozygous familial hypercholesterolaemia

Knops

Mol

Stuyt

et al. 1995

The Netherlands Journal of Medicine

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Objective: To study the long-term efficacy and safety of the cholesterol synthesis inhibitor, simvastatin, in the treatment of familial hypercholesterolaemia.Methods: This is an open long-term follow-up of patients treated for 5 years or more in the Nijmegen University lipid clinic. Forty-four patients with heterozygous familial hypercholesterolaemia (mean baseline serum cholesterol level 11.5 mmol/1) were treated with simvastatin alone (monotherapy group) in doses ranging from 20 to 80 mg/day, or in combination with other lipid-lowering agents (combination-therapy group).Results: Over the intervention period of 6 years the mean overall reduction of the serum cholesterol level was 37.8% for the total group, 37.7% for the monotherapy group and 42.6% for the combination-therapy group. The reduction of the low-density lipoprotein (LDL)-cholesterol in the three groups was 45.0, 44.6 and 50.3%, respec tively. The serum triglyceride concentration was reduced by 14.0, 20.5 and 12.5%, respectively. The increase in the high-density lipoprotein (HDL)-cholesterol level was 14.4, 16.2 and 14.0%, respectively. One patient died from a myocardial infarction and 2 patients had a non-fatal cardiac event. Two patients stopped taking medication due to side-effects (dizziness and insomnia). Biochemical adverse effects were confined to elevations of the alanine aminotransferase level and the creatine phosphokinase level and did not lead to discontinuation of therapy.Conclusions: Simvastatin proves to be a safe and effective lipid-lowering drug during long-term treatment.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 72%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term experience (6 years) with simvastatin in patients with heterozygous familial hypercholesterolaemia

Knops

Mol

Stuyt

et al. 1995

The Netherlands Journal of Medicine

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“…Further purification was achieved by a second ultracentrifugation step. On the LDL-containing fraction 1 ml EDTA-containing (0.1 g I-') saline with density 1.10 g mi-' (133.5 g KBr I -I) was layered, and subsequently centrifuged at 36000 rpm for 18 h at 15°C.…”

Section: Ldl Isolationmentioning

confidence: 99%

Decreased in vitro oxidizability of low‐density lipoprotein in hypercholesterolaemic patients treated with 3‐hydroxy‐3‐methyIgIutaryl‐CoA reductase inhibitors

Kleinveld

Demacker

Haan

et al. 1993

Eur J Clin Investigation

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Abstract. We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simvastatin and pravastatin on the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation. Twenty-three hypercholesterolaemic patients (mean serum cholesterol 9.7 mmol 1-') were treated with increasing doses of either simvastatin or pravastatin for 18 weeks. No significant differences in effect on lipid levels between the two drugs were found. Treatment resulted in lowering of total cholesterol and LDL-cholesterol by maximally 30% and 34%, respectively. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl-ester after treatment. The LDL cholesterol/protein ratio decreased from 1.24 f 0.21 to 0.97 f 0.23 (n = 20). By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidation after drug treatment. Maximal rate of diene production was significantly decreased from 19.7f 3.1 to 18.5 f 3.3 nmol min-l mg-' LDL; total diene production decreased significantly from 420.3k67.6 to 380.5k49.1 nmol mg-l LDL; the lag time was unchanged throughout the study. These studies show that HMG-CoA reductase inhibitors reduce the oxidizability of LDL by altering its composition.

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Pravastatin vs Gemfibrozil in the Treatment of Primary Hypercholesterolemia

Crepaldi

Baggio²,

Arca³

et al. 1991

Arch Intern Med

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Effects of Synvinolin (Mk-733) on Plasma Lipids in Familial Hypercholesterolaemia

Cited by 153 publications

References 25 publications

Long-term experience (6 years) with simvastatin in patients with heterozygous familial hypercholesterolaemia

Long-term experience (6 years) with simvastatin in patients with heterozygous familial hypercholesterolaemia

Decreased in vitro oxidizability of low‐density lipoprotein in hypercholesterolaemic patients treated with 3‐hydroxy‐3‐methyIgIutaryl‐CoA reductase inhibitors

Pravastatin vs Gemfibrozil in the Treatment of Primary Hypercholesterolemia

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