Copyright © 1997 by the European Society of Cardiology.
© 1997 The European Society of Cardiology
Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids
*MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, The Medical College of St. Bartholomew's Hospital London, U.K.
MRC/BHF/ICRF Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, Radcliffe Infirmary Oxford, U.K.
revised 19 February 1996; accepted 26 July 1996.
Correspondence: Dr K. A. Mitropoulos, MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, The Medical College of St. Bartholomew's Hospital, Charterhouse Square, London EC1M 6BQ, U.K.
Abstract
The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously.
At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo.
Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12·10%±6·08 of standard; 2P<0·05) and non-significantly lower factor VII coagulant activity (8·24%±4·99 of standard) and fibrinogen concentrations (0·10±0·08 g.l–1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2·62±1·03 IU; 2P<0·01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1·2, factor XII and C$$$ inhibitor). Total free fatty acid concentration was marginally significantly reduced (2P=0·02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1·74±0·15 mmol.1–1; 2P<0·0001) but also in VLDL cholesterol (0·28±0·08 mmol.1–1; 2P<0·001) and IDL cholesterol (0·17±0·03 mmol.1–1; 2P<0·0001). There were also lower triglyceride levels associated with LDL (0·07±0·01 mmol.1–1; 2P<0·0001), IDL (0·03±0·01 mmol.1–1; 2P<0·01) and VLDL (0·27±0·14; 2P=0·05).
The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA re1ductase inhibitors (and of the newer fibrates, which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.
Key Words: Haemostatic variables • fatty acids • simvastatin • randomized trial
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. W. Rabkin and P. Lodha Stearic acid-induced cardiac lipotoxicity is independent of cellular lipid and is mitigated by the fatty acids oleic and capric acid but not by the PPAR agonist troglitazone Exp Physiol, August 1, 2009; 94(8): 877 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Nogueira and M. Weir The Unique Character of Cardiovascular Disease in Chronic Kidney Disease and Its Implications for Treatment with Lipid-Lowering Drugs Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(4): 766 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Golomb, M. H. Criqui, H. White, and J. E. Dimsdale Conceptual Foundations of the UCSD Statin Study: A Randomized Controlled Trial Assessing the Impact of Statins on Cognition, Behavior, and Biochemistry Arch Intern Med, January 26, 2004; 164(2): 153 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Balk, J. Lau, L. C. Goudas, H. S. Jordan, B. Kupelnick, L. U. Kim, and R. H. Karas Effects of Statins on Nonlipid Serum Markers Associated with Cardiovascular Disease: A Systematic Review Ann Intern Med, October 21, 2003; 139(8): 670 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kadikoylu, V. Yukselen, I. Yavasoglu, and Z. Bolaman Hemostatic Effects of Atorvastatin Versus Simvastatin Ann. Pharmacother., April 1, 2003; 37(4): 478 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-M. Mu, T. Yanase, Y. Nishi, A. Tanaka, M. Saito, C.-H. Jin, C. Mukasa, T. Okabe, M. Nomura, K. Goto, et al. Saturated FFAs, Palmitic Acid and Stearic Acid, Induce Apoptosis in Human Granulosa Cells Endocrinology, August 1, 2001; 142(8): 3590 - 3597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Park and J. B. Galper 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors up-regulate transforming growth factor-beta signaling in cultured heart cells via inhibition of geranylgeranylation of RhoA GTPase PNAS, September 28, 1999; 96(20): 11525 - 11530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Gotto Jr and S. M. Grundy Lowering LDL Cholesterol : Questions From Recent Meta-Analyses and Subset Analyses of Clinical Trial DataIssues From the Interdisciplinary Council on Reducing the Risk for Coronary Heart Disease, Ninth Council Meeting Circulation, March 2, 1999; 99 (8): e1 - e7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Rosenson and C. C. Tangney Antiatherothrombotic Properties of Statins: Implications for Cardiovascular Event Reduction JAMA, May 27, 1998; 279(20): 1643 - 1650. [Abstract] [Full Text] [PDF]
|
|