Atherosclerosis 151 (2000) 591 – 592
Letter to the Editor
www.elsevier.com/locate/atherosclerosis
More on atorvastatin and fibrinogen
It is an ongoing discussion whether atorvastatin may
increase fibrinogen concentrations in patients with
hy-perlipidemia. In their letter to the editor Wierzbicki and
collegues presumed that atorvastatin increases
fibrino-gen concentration in specific patient populations [1].
We think that this conclusion is not justified regarding
the data published so far.
It is remarkable that increases in fibrinogen levels
were observed especially in uncontrolled trials, whereas
contradicting results were obtained from controlled
in-vestigations. In Table 1 we have summarized the
stud-ies, in which fibrinogen concentration was measured
after atorvastatin, and we have indicated which studies
had a controlled design. Since fibrinogen concentration
is difficult to measure and an international standard is
not generally available so far, controlled studies are
required to investigate the effect of a drug on fibrinogen
concentration in order to avoid possible systematical
errors, such as assay drifts.
With the exception of the study of Wierzbicki and
collegues published last year [2], controlled trials did
not show a significant increase in fibrinogen
concentra-tion after atorvastatin. Therefore, controlled,
prospec-tive and randomized trials are needed with fibrinogen
concentration as a primary end point. We think that
until now, an increase in fibrinogen concentration after
atorvastatin therapy has not been proven.
References
[1] Wierzbicki AS, Crook MA, Nair DR, Mikhailidis DP, Winder AF. More on the effect of atorvastatin on plasma fibrinogen levels in primary hypercholesterolemia. Atherosclerosis 2000; 148: 204.
[2] Wierzbicki AS, Lumb PJ, Sernra Y, et al. Atorvastati compared with simvastatin-based therapies in the management of severe familial hyperlipidaemias. QJM 1999; 92: 387 – 394.
[3] Marais AD, Firth JC, Bateman ME, et al. Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 1997; 17: 1527 – 1531.
[4] Wierzbicki AS, Lumb PJ, Semra YK, Crook MA. Effect of atorvastatin on plasma fibrinogen. Lancet 1998; 351: 569 – 570.
[5] Nair DR, Papadakis JA, Jagroop IA, Mikhailidis DP, Winder AF. Statins and fibrinogen. Lancet 1998; 351: 1430.
[6] Bertolotto A, Bandinelli S, Ruocco L, et al. More on the effect of atorvastatin on plasma fibrinogen levels in primary hyper-cholesterolemia. Atherosclerosis 1999; 143: 455 – 457.
[7] Davidson M, McKenney J, Stein E, et al. For the Atorvastatin Study Group 1. Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Am J Cardiol 1997; 79: 1475 – 1481.
[8] Jones P, Kafonek S, Laurora I, Hunninghake D. For the CURVES Investigators. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES Study). Am J Cardiol 1998; 81: 582 – 587.
[9] Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Athy-rou VV, Kontopoulos AG. Effect of atorvastatin versus simva-statin on lipid profile and plasma fibrinogen in patients with hypercholesterolaemia. A pilot, randomized, double-blind, dose-titrating study. Clin Drug Invest 1998; 16: 219 – 227.
Table 1
Studies which investigated the effect of atorvastatin on fibrinogen levels
Change in fibrinogen level
Author Number of patients Controlled design
No
Bertolotto [6] +26% No
730
Otto [10] 9 No change Yes
56 No change
Bakker [11] Yes
201
Wierzbicki [2] +12–20% Yes
Letter to the Editor 592
[10] Otto C, Geiss HC, Donner MG, Parhofer KG, Schwandt P. Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hyper-cholesterolemia treated with regular immunoadsorption apheresis. Ther Apheresis 2151 (in press).
[11] Bakker-Arkema RG, Davidson MH, Goldstein RJ, et al., Effi-cacy and safety of a new HMG-CoA reductase inhibitor, ator-vastatin in patients with hypertriglyceridemia. JAMA 1996; 275: 128 – 133.
