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Statins and fibrinogen

1998; Elsevier BV; Volume: 351; Issue: 9113 Linguagem: Inglês

10.1016/s0140-6736(98)26019-3

1474-547X

DR Nair, John A. Papadakis, IA Jagroop, D.P. Mikhailidis, AF Winder,

Antiplatelet Therapy and Cardiovascular Diseases

We have measured (Clauss method) fibrinogen levels in 23 patients before and 2 months after atorvastatin 10 mg daily. 17 patients had established vascular disease. The plasma fibrinogen rose (19·3%) from a median of 3·37 (range 2·02–4·93) to 4·02 (1·93–7·18) g/L (p=0·005; two-tailed Wilcoxon test).We also measured serum lipoprotein(a), another predictor of vascular events, in 21 patients. We selected baseline values of 0·30 g/L or more because assay reproducibility is poor at lower values. Lipoprotein(a) concentrations rose (20·6%) from 0·63 (0·30–1·08) to 0·76 (0·36–1·40), g/L (p=0·01).Statins exert variable effects on fibrinogen, and other workers1Wierzbicki AS Lumb PJ Semra YK Crook MA Effect of atorvastatin on plasma fibrinogen.Lancet. 1998; 351: 569-570Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 2Bakker-Arkema RG Davidson MH Goldstein RJ et al.Efficacy and safety of a new HMG-CoA reductace inhibitor, atorvastatin, in patients with hypertriglyceridemia.JAMA. 1996; 275: 128-133Crossref PubMed Google Scholar have reported that atorvastatin does not raise plasma fibrinogen, with data up to 1 year. The effect of statins on lipoprotein(a) has been less extensively studied. A correlation between fibrinogen and lipoprotein(a) concentrations has been reported,3Heinrich J Sandkamp M Kokott R Schulte H Assmann G Relationship of lipoprotein (a) to variables of coagulation and fibrinolysis in a healthy population.Clin Chem. 1991; 37: 1950-1954PubMed Google Scholar so it is interesting that concentration of both rise after atorvastatin. Our observations, together with those of Anthony Wierzbicki et al (Feb 21, p 351),1Wierzbicki AS Lumb PJ Semra YK Crook MA Effect of atorvastatin on plasma fibrinogen.Lancet. 1998; 351: 569-570Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar may be clinically relevant because fibrinogen and lipoprotein(a) predict vascular events.1Wierzbicki AS Lumb PJ Semra YK Crook MA Effect of atorvastatin on plasma fibrinogen.Lancet. 1998; 351: 569-570Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 2Bakker-Arkema RG Davidson MH Goldstein RJ et al.Efficacy and safety of a new HMG-CoA reductace inhibitor, atorvastatin, in patients with hypertriglyceridemia.JAMA. 1996; 275: 128-133Crossref PubMed Google Scholar, 3Heinrich J Sandkamp M Kokott R Schulte H Assmann G Relationship of lipoprotein (a) to variables of coagulation and fibrinolysis in a healthy population.Clin Chem. 1991; 37: 1950-1954PubMed Google Scholar, 4Thompson SG Kienast J Pyke SD Haverkate F van der Loo JC Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.N Engl J Med. 1995; 332: 635-641Crossref PubMed Scopus (1590) Google Scholar, 5Maher VM Brown BG Marcovina SM Hilger LA Zhao XQ Albers JJ Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a).JAMA. 1995; 274: 1771-1774Crossref PubMed Scopus (281) Google Scholar Furthermore, low-density lipoprotein (LDL) and fibrinogen act synergistically, in terms of cardiovascular risk prediction, in healthy individuals and patients with ischaemic heart disease.4Thompson SG Kienast J Pyke SD Haverkate F van der Loo JC Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.N Engl J Med. 1995; 332: 635-641Crossref PubMed Scopus (1590) Google Scholar Lipoprotein(a) seems to act synergistically with LDL.5Maher VM Brown BG Marcovina SM Hilger LA Zhao XQ Albers JJ Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a).JAMA. 1995; 274: 1771-1774Crossref PubMed Scopus (281) Google ScholarThere is a need for properly designed trials to define the effect of statins on all predictive haemostatic variables. We have measured (Clauss method) fibrinogen levels in 23 patients before and 2 months after atorvastatin 10 mg daily. 17 patients had established vascular disease. The plasma fibrinogen rose (19·3%) from a median of 3·37 (range 2·02–4·93) to 4·02 (1·93–7·18) g/L (p=0·005; two-tailed Wilcoxon test). We also measured serum lipoprotein(a), another predictor of vascular events, in 21 patients. We selected baseline values of 0·30 g/L or more because assay reproducibility is poor at lower values. Lipoprotein(a) concentrations rose (20·6%) from 0·63 (0·30–1·08) to 0·76 (0·36–1·40), g/L (p=0·01). Statins exert variable effects on fibrinogen, and other workers1Wierzbicki AS Lumb PJ Semra YK Crook MA Effect of atorvastatin on plasma fibrinogen.Lancet. 1998; 351: 569-570Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 2Bakker-Arkema RG Davidson MH Goldstein RJ et al.Efficacy and safety of a new HMG-CoA reductace inhibitor, atorvastatin, in patients with hypertriglyceridemia.JAMA. 1996; 275: 128-133Crossref PubMed Google Scholar have reported that atorvastatin does not raise plasma fibrinogen, with data up to 1 year. The effect of statins on lipoprotein(a) has been less extensively studied. A correlation between fibrinogen and lipoprotein(a) concentrations has been reported,3Heinrich J Sandkamp M Kokott R Schulte H Assmann G Relationship of lipoprotein (a) to variables of coagulation and fibrinolysis in a healthy population.Clin Chem. 1991; 37: 1950-1954PubMed Google Scholar so it is interesting that concentration of both rise after atorvastatin. Our observations, together with those of Anthony Wierzbicki et al (Feb 21, p 351),1Wierzbicki AS Lumb PJ Semra YK Crook MA Effect of atorvastatin on plasma fibrinogen.Lancet. 1998; 351: 569-570Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar may be clinically relevant because fibrinogen and lipoprotein(a) predict vascular events.1Wierzbicki AS Lumb PJ Semra YK Crook MA Effect of atorvastatin on plasma fibrinogen.Lancet. 1998; 351: 569-570Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 2Bakker-Arkema RG Davidson MH Goldstein RJ et al.Efficacy and safety of a new HMG-CoA reductace inhibitor, atorvastatin, in patients with hypertriglyceridemia.JAMA. 1996; 275: 128-133Crossref PubMed Google Scholar, 3Heinrich J Sandkamp M Kokott R Schulte H Assmann G Relationship of lipoprotein (a) to variables of coagulation and fibrinolysis in a healthy population.Clin Chem. 1991; 37: 1950-1954PubMed Google Scholar, 4Thompson SG Kienast J Pyke SD Haverkate F van der Loo JC Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.N Engl J Med. 1995; 332: 635-641Crossref PubMed Scopus (1590) Google Scholar, 5Maher VM Brown BG Marcovina SM Hilger LA Zhao XQ Albers JJ Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a).JAMA. 1995; 274: 1771-1774Crossref PubMed Scopus (281) Google Scholar Furthermore, low-density lipoprotein (LDL) and fibrinogen act synergistically, in terms of cardiovascular risk prediction, in healthy individuals and patients with ischaemic heart disease.4Thompson SG Kienast J Pyke SD Haverkate F van der Loo JC Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.N Engl J Med. 1995; 332: 635-641Crossref PubMed Scopus (1590) Google Scholar Lipoprotein(a) seems to act synergistically with LDL.5Maher VM Brown BG Marcovina SM Hilger LA Zhao XQ Albers JJ Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a).JAMA. 1995; 274: 1771-1774Crossref PubMed Scopus (281) Google Scholar There is a need for properly designed trials to define the effect of statins on all predictive haemostatic variables. Statins and fibrinogenAuthors' reply Full-Text PDF