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. 1991 Mar;31(3):340–343. doi: 10.1111/j.1365-2125.1991.tb05539.x

Simvastatin in severe hypercholesterolaemia: a placebo controlled trial.

I F McDowell 1, M Smye 1, T Trinick 1, J A Shortt 1, M P Archibald 1, E R Trimble 1, D P Nicholls 1
PMCID: PMC1368362  PMID: 2054273

Abstract

The effect of simvastatin in 27 patients with severe primary hypercholesterolaemia was assessed by a double-blind placebo controlled parallel group trial. Total serum cholesterol, LDL-cholesterol and apoprotein B (ApoB) were significantly reduced by simvastatin 40 mg daily. Reductions in triglyceride and VLDL-cholesterol and an increase in HDL-cholesterol levels were only significant when calculated as a percentage of baseline, because of wide inter-individual variability. No changes in apoprotein A1, lipoprotein (a), fibrinogen, viscosity or blood pressure were observed. Leucocyte HMG-CoA reductase activity was unchanged after 4 weeks of active treatment but increased by 87% after 3 months (n = 21, P less than 0.05). No severe adverse effects or changes in CK or AST levels were noted. We conclude that simvastatin is effective in the treatment of severe and resistant hypercholesterolaemia, and well tolerated in the short term.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avellone G., Di Garbo V., Panno A. V., Cordova R., Lepore R., Strano A. Changes induced by gemfibrozil on lipidic, coagulative and fibrinolytic pattern in patients with type IV hyperlipoproteinemia. Int Angiol. 1988 Jul-Sep;7(3):270–277. [PubMed] [Google Scholar]
  2. Beg Z. H., Brewer H. B., Jr Modulation of rat liver 3-hydroxy-3-methylglutaryl-CoA reductase activity by reversible phosphorylation. Fed Proc. 1982 Aug;41(10):2634–2638. [PubMed] [Google Scholar]
  3. Berg K., Leren T. P. Unchanged serum lipoprotein (a) concentrations with lovastatin. Lancet. 1989 Sep 30;2(8666):812–812. doi: 10.1016/s0140-6736(89)90884-2. [DOI] [PubMed] [Google Scholar]
  4. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  5. CLAUSS A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol. 1957 Apr;17(4):237–246. doi: 10.1159/000205234. [DOI] [PubMed] [Google Scholar]
  6. Ferrier C., Weidmann P., Hollmann R., Dietler R., Shaw S. Impaired response of atrial natriuretic factor to high salt intake in persons prone to hypertension. N Engl J Med. 1988 Nov 3;319(18):1223–1224. doi: 10.1056/NEJM198811033191812. [DOI] [PubMed] [Google Scholar]
  7. Goldstein J. L., Brown M. S. Regulation of the mevalonate pathway. Nature. 1990 Feb 1;343(6257):425–430. doi: 10.1038/343425a0. [DOI] [PubMed] [Google Scholar]
  8. Grundy S. M. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med. 1988 Jul 7;319(1):24–33. doi: 10.1056/NEJM198807073190105. [DOI] [PubMed] [Google Scholar]
  9. HARKNESS J. A new instrument for the measurement of plasma-viscosity. Lancet. 1963 Aug 10;2(7302):280–281. doi: 10.1016/s0140-6736(63)90177-6. [DOI] [PubMed] [Google Scholar]
  10. Hagemenas F. C., Pappu A. S., Illingworth D. R. The effects of simvastatin on plasma lipoproteins and cholesterol homeostasis in patients with heterozygous familial hypercholesterolaemia. Eur J Clin Invest. 1990 Apr;20(2):150–157. doi: 10.1111/j.1365-2362.1990.tb02262.x. [DOI] [PubMed] [Google Scholar]
  11. Harwood H. J., Jr, Schneider M., Stacpoole P. W. Measurement of human leukocyte microsomal HMG-CoA reductase activity. J Lipid Res. 1984 Sep;25(9):967–978. [PubMed] [Google Scholar]
  12. Houlston R., Friedl W. Biochemistry and clinical significance of lipoprotein (a). Ann Clin Biochem. 1988 Sep;25(Pt 5):499–503. doi: 10.1177/000456328802500504. [DOI] [PubMed] [Google Scholar]
  13. Jürgens G., Ashy A., Zenker G. Raised serum lipoprotein during treatment with lovastatin. Lancet. 1989 Apr 22;1(8643):911–912. doi: 10.1016/s0140-6736(89)92921-8. [DOI] [PubMed] [Google Scholar]
  14. Leclercq V., Harvengt C. Simvastatin (MK 733) in heterozygous familial hypercholesterolemia: a two-year trial. Int J Clin Pharmacol Ther Toxicol. 1989 Feb;27(2):76–81. [PubMed] [Google Scholar]
  15. Meade T. W., Mellows S., Brozovic M., Miller G. J., Chakrabarti R. R., North W. R., Haines A. P., Stirling Y., Imeson J. D., Thompson S. G. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet. 1986 Sep 6;2(8506):533–537. doi: 10.1016/s0140-6736(86)90111-x. [DOI] [PubMed] [Google Scholar]
  16. Mol M. J., Erkelens D. W., Gevers Leuven J. A., Schouten J. A., Stalenhoef A. F. Simvastatin (MK-733): a potent cholesterol synthesis inhibitor in heterozygous familial hypercholesterolaemia. Atherosclerosis. 1988 Feb;69(2-3):131–137. doi: 10.1016/0021-9150(88)90006-8. [DOI] [PubMed] [Google Scholar]
  17. Mol M. J., Erkelens D. W., Leuven J. A., Schouten J. A., Stalenhoef A. F. Effects of synvinolin (MK-733) on plasma lipids in familial hypercholesterolaemia. Lancet. 1986 Oct 25;2(8513):936–939. doi: 10.1016/s0140-6736(86)90598-2. [DOI] [PubMed] [Google Scholar]
  18. Mölgaard J., von Schenck H., Olsson A. G. Effects of simvastatin on plasma lipid, lipoprotein and apolipoprotein concentrations in hypercholesterolaemia. Eur Heart J. 1988 May;9(5):541–551. doi: 10.1093/oxfordjournals.eurheartj.a062541. [DOI] [PubMed] [Google Scholar]
  19. Niort G., Bulgarelli A., Cassader M., Pagano G. Effect of short-term treatment with bezafibrate on plasma fibrinogen, fibrinopeptide A, platelet activation and blood filterability in atherosclerotic hyperfibrinogenemic patients. Atherosclerosis. 1988 Jun;71(2-3):113–119. doi: 10.1016/0021-9150(88)90135-9. [DOI] [PubMed] [Google Scholar]
  20. Stewart J. M., Packard C. J., Lorimer A. R., Boag D. E., Shepherd J. Effects of bezafibrate on receptor-mediated and receptor-independent low density lipoprotein catabolism in type II hyperlipoproteinaemic subjects. Atherosclerosis. 1982 Sep;44(3):355–365. doi: 10.1016/0021-9150(82)90010-7. [DOI] [PubMed] [Google Scholar]
  21. Wiklund O., Angelin B., Olofsson S. O., Eriksson M., Fager G., Berglund L., Bondjers G. Apolipoprotein(a) and ischaemic heart disease in familial hypercholesterolaemia. Lancet. 1990 Jun 9;335(8702):1360–1363. doi: 10.1016/0140-6736(90)91242-3. [DOI] [PubMed] [Google Scholar]

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