- Email: [email protected]
Effect of fluvastatin on plasma fibrinogen levels
Thursday, 27 May 1999 Poster session: Lipid lowering drugs
37
CERIVASTATIN-INDUCED REDUCTION IN PLASMA TRIGLYCERIDES IS DIRECTLY RELATED TO BASELINE LEVELS
EFFECT OF FLUVASTATIN ON PLASMA FIBRINOGEN LEVELS
E. Stein, U. Schopen 1, M. Catagay 1, R. Ziegler 1. Medical Research Laboratories. Kentuc~: USA," /Bayer AG, Germam,
/ Biochemistr3, Laboratory. Medical School, University of loannina. Ioannina, Greece
Objective: To investigate the effects ofcerivastatin (an HMG-CoA reductase inhibitor) on plasma triglyceride (TG) levels in a large patient population with primary hypercholesterolaemia. Methods: A pooled analysis was performed using data from 6 randomised, double-blind, parallel studies. In these studies, cerivastatin (0.1 to 0.4 rag/day) or placebo was administered to 3374 patients with primary hypercholesterolaemia for a period of 8 to 24 weeks. Treatment was preceded by a 10-week diet-controlled run-in period. Patients were evaluated at weeks 8, 16 and 24. Fasting TG levels at endpoint were evaluated in relation to the corresponding baseline TG levels Results: The results from an intention-to-treat analysis showed that in general, for cerivastatin doses at 8, 16 and 24 weeks, higher baseline TG levels were associated with greater reductions in plasma TGs. The maximum decrease in TG levels was observed in patients with baseline TG > 300 mg/dl. Mean TG reductions at week 8 are presented in the table; however it is important to note that, following treatment with cerivastatin, very high reductions in plasma TG levels (up to -80%) were recorded in individual patients.
There are conflicting data concerning the influence of statins on fibrinogen levels. It has been reported that atorvastatin can significantly increase plasma fibrinogen levels, though these results have been questioned, since they may be related to differences in patients' selection, to the assays used, or to other confounding factors, such as smoking status or seasonal variation of plasma fibrinogen levels. To the best of our knowledge there are no data regarding the influence of fluvastatin on flbrinogen levels. We have measured (Clauss method) plasma fibrinogen levels in 65 hypercholesterolemic non smoking patients with normal triglycerides (<2.25 mmol/L) before and 6 weeks after fluvastatin 40 mg daily. A significant decrease by 8% in plasma fibrinogen levels was observed from a median of 3.62 g/L (range, 2.27-5.60 g/L) to a median of 3.33 g/L (range, 2.09-5.60 g/L), p < 0.02 by a two-tailed Wilcoxon signed-rank test. No correlation was found between the changes in plasma lipid parameters and those in plasma fibrinogen. Additionally, there was no correlation between the baseline plasma flbrinogen levels and the observed changes in fibrinogen levels after fluvastatin administration. Our results reinforce the importance of further controlled studies, including clinical events and mortality data, to assess the long-term influence of different statins on fibrinogen levels, the underlying mechanisms, as well as the putative importance of this effect.
Table l: Mean decrease in plasma T G levels following 8 weeks cerlvastatin ireatment Cerlvastatln Mean change in plasma trlglycerlde (TG} dote 200-300 mg/dl base-, (mg/dayl ~200 mg/dl baseline T G Ilne T G %
t'~ l
263
-7.9
Iol
- t 1.8
64
-18.7
ft2
3q'3
-I08
199
-21.1
61
-13.5
03
377
- 1 1.3
221
- 19,2
64
-27.5
114
666
Placebo
456
n
l 1.2 +5.9
%
>300 mg/dl baseline T G
n
n
E. Liberopoulos, V. Tsimihodimos, E. Bairaktari I , Ch. Tzallas 1, E. Rizos, A. Katsaraki, G. Miltiadous, M. Elisaf. Department oflnternal Medicine;
HOW ACHIEVABLE IS THE DESIRABLE REDUCTION OF LDL CHOLESTEROL IN CORONARY PATIENTS: EXPERIENCE FROM A DISTRICT GREEK HOSPITAL
%
189
-175
34
-286
185
-0.5
41
+75
Conclusion: This pooled data analysis demonstrates that cerivastatin is effective in the reduction of plasma TG levels. Furthermore, the magnitude of reduction in plasma TG following daily treatment with 0.1 to 0.4 mg cerivastatin is, in general, related to baseline TG levels.
COMPARISON OF THE EFFICACY OF ATORVASTATIN AND MICRONISED FENOFIBRATE IN THE TREATMENT OF MIXED HYPERLIPIDEMIA G. Miltiadous, E. Bairaktari 1, C. Tzallas 1, V. Tsimihodimos, E. Liberopoulos, H. Milionis, E. Rizos, M. Elisaf. Department of Internal
Medicine: t BiochemistD, Laborator3,. Medical School. UniversiO' of Ioannina, loannina, Greece We undertook the present study to evaluate and compare the influence of micronized fenofibrate vs atorvastatin on serum lipid profile, including Lp(a) levels, and on fibrinogen levels in a large group of patients with primary mixed hyperlipidemia (serum total and LDL cholesterol levels > 240 and 160 mg/dI, respectively and serum triglycerides > 200 mg/dl). It was a 16 week randomised, open-label, parallel design study conducted in our lipid clinic. A 6 week dietary baseline phase was followed by a treatment phase, in which patients received atorvastatin 10 mg/day (n = 45) or micronised fenofibrate 200 mg/day (n = 46) for 16 weeks. Patients were randomly assigned to one of the drugs in sequence orders. Serum lipid profile, including Lp(a), fibrinogen levels, as well as muscle and liver enzymes were measured at screening, at weeks -4, -2, 0 (randomisation) and at 8 and 16 weeks during the treatment period. Atorvastatin was more effective than micronised fenofibrate at lowering total and LDL cholesterol levels, while fenofibrate was more effective at lowering triglycerides and raising HDL cholesterol and ApoAl levels. However, micronised fenofibrate could significantly decrease plasma fibrinogen levels, while atorvastatin evoked a small increase. We conclude that both atorvastatin in small doses and micronised fenofibrate are effective in the improvement of serum lipid profile in patients with mixed hyperlipidemia. However, there are considerable differences between the two drugs concerning their influence on plasma fibrinogen levels.
L. Rallidis, M. Zolindakis 1 . T. Andoniadis, K. Thomaidis, E. Denezos 1, E. Papasteriadis, G. Tsitouris 2. j 1st Department of Cardiology and
Biochemistry Laboratory," General Hospital of Nikea. Piraeus: 22nd Department of CardioloKv; Eoangelismos Hospital. Athens. Greece Introduction: despite the documented benefit of aggressive lipid lowering treatment in secondary prevention of coronary artery disease, several studies have suggested suboptimal lipid management. We aimed to assess how achievable are the targets of lipid lowering treatment in coronary patients in relation to the European (LDL cholesterol < 115 mg/dl) and US (LDL cholesterol < 100 mg/dl) guidelines. Methods: we measured fasting lipids in 2 [6 consecutive patients who attended our outpatient cardiology department. All these patients had suffered a myocardial infarction. Patients with a recent myocardial infarction (<4 months) were excluded. Results: the mean levels of lipids were as follows: total cholesterol = 230 +47 mg/dl, triglycerides = 164+80 mg/dl, LDL cholesterol = 157+35 mg/dl and HDL cholesterol = 38.7±9 mg/dl. Forty-eight (,22.2%) patients were taking a regular hypolipidaemic treatment (30 on statins and the remaining on fibrates or combination of fibrates and statins). In addition, 20 patients had taken only occasionally hypolipidaemic treatment in the past. The table indicates the number of patients with LDL cholesterol < 100 mg/dl, <115 mg/dl and _>130 mg/dl in relation to the regular administration of lipid lowering treatment: Lipid towering treatment
n
Yes No
LDL cholesterol <100 mg/d|
LDL cholesterol
LDL choleslerot >_130 mg/dl
48
I (2A%)
6 (12.5%)
37 {77A%)
168
7 (4.2%)
17 ( 10. 1%)
134 (79.8%)
NS
NS
NS
p
Conclusions: a) a small number of coronary patients requiting lipid lowering treatment is receiving regular hypolipidaemic treatment and b) even those who are treated rarely achieve the lipid goals set by the committees and this underlines the need for more aggressive hypolipidaemic policy.
71st EAS Congress and Satellite Symposia
m
2 C
6 C
37
CERIVASTATIN-INDUCED REDUCTION IN PLASMA TRIGLYCERIDES IS DIRECTLY RELATED TO BASELINE LEVELS
EFFECT OF FLUVASTATIN ON PLASMA FIBRINOGEN LEVELS
E. Stein, U. Schopen 1, M. Catagay 1, R. Ziegler 1. Medical Research Laboratories. Kentuc~: USA," /Bayer AG, Germam,
/ Biochemistr3, Laboratory. Medical School, University of loannina. Ioannina, Greece
Objective: To investigate the effects ofcerivastatin (an HMG-CoA reductase inhibitor) on plasma triglyceride (TG) levels in a large patient population with primary hypercholesterolaemia. Methods: A pooled analysis was performed using data from 6 randomised, double-blind, parallel studies. In these studies, cerivastatin (0.1 to 0.4 rag/day) or placebo was administered to 3374 patients with primary hypercholesterolaemia for a period of 8 to 24 weeks. Treatment was preceded by a 10-week diet-controlled run-in period. Patients were evaluated at weeks 8, 16 and 24. Fasting TG levels at endpoint were evaluated in relation to the corresponding baseline TG levels Results: The results from an intention-to-treat analysis showed that in general, for cerivastatin doses at 8, 16 and 24 weeks, higher baseline TG levels were associated with greater reductions in plasma TGs. The maximum decrease in TG levels was observed in patients with baseline TG > 300 mg/dl. Mean TG reductions at week 8 are presented in the table; however it is important to note that, following treatment with cerivastatin, very high reductions in plasma TG levels (up to -80%) were recorded in individual patients.
There are conflicting data concerning the influence of statins on fibrinogen levels. It has been reported that atorvastatin can significantly increase plasma fibrinogen levels, though these results have been questioned, since they may be related to differences in patients' selection, to the assays used, or to other confounding factors, such as smoking status or seasonal variation of plasma fibrinogen levels. To the best of our knowledge there are no data regarding the influence of fluvastatin on flbrinogen levels. We have measured (Clauss method) plasma fibrinogen levels in 65 hypercholesterolemic non smoking patients with normal triglycerides (<2.25 mmol/L) before and 6 weeks after fluvastatin 40 mg daily. A significant decrease by 8% in plasma fibrinogen levels was observed from a median of 3.62 g/L (range, 2.27-5.60 g/L) to a median of 3.33 g/L (range, 2.09-5.60 g/L), p < 0.02 by a two-tailed Wilcoxon signed-rank test. No correlation was found between the changes in plasma lipid parameters and those in plasma fibrinogen. Additionally, there was no correlation between the baseline plasma flbrinogen levels and the observed changes in fibrinogen levels after fluvastatin administration. Our results reinforce the importance of further controlled studies, including clinical events and mortality data, to assess the long-term influence of different statins on fibrinogen levels, the underlying mechanisms, as well as the putative importance of this effect.
Table l: Mean decrease in plasma T G levels following 8 weeks cerlvastatin ireatment Cerlvastatln Mean change in plasma trlglycerlde (TG} dote 200-300 mg/dl base-, (mg/dayl ~200 mg/dl baseline T G Ilne T G %
t'~ l
263
-7.9
Iol
- t 1.8
64
-18.7
ft2
3q'3
-I08
199
-21.1
61
-13.5
03
377
- 1 1.3
221
- 19,2
64
-27.5
114
666
Placebo
456
n
l 1.2 +5.9
%
>300 mg/dl baseline T G
n
n
E. Liberopoulos, V. Tsimihodimos, E. Bairaktari I , Ch. Tzallas 1, E. Rizos, A. Katsaraki, G. Miltiadous, M. Elisaf. Department oflnternal Medicine;
HOW ACHIEVABLE IS THE DESIRABLE REDUCTION OF LDL CHOLESTEROL IN CORONARY PATIENTS: EXPERIENCE FROM A DISTRICT GREEK HOSPITAL
%
189
-175
34
-286
185
-0.5
41
+75
Conclusion: This pooled data analysis demonstrates that cerivastatin is effective in the reduction of plasma TG levels. Furthermore, the magnitude of reduction in plasma TG following daily treatment with 0.1 to 0.4 mg cerivastatin is, in general, related to baseline TG levels.
COMPARISON OF THE EFFICACY OF ATORVASTATIN AND MICRONISED FENOFIBRATE IN THE TREATMENT OF MIXED HYPERLIPIDEMIA G. Miltiadous, E. Bairaktari 1, C. Tzallas 1, V. Tsimihodimos, E. Liberopoulos, H. Milionis, E. Rizos, M. Elisaf. Department of Internal
Medicine: t BiochemistD, Laborator3,. Medical School. UniversiO' of Ioannina, loannina, Greece We undertook the present study to evaluate and compare the influence of micronized fenofibrate vs atorvastatin on serum lipid profile, including Lp(a) levels, and on fibrinogen levels in a large group of patients with primary mixed hyperlipidemia (serum total and LDL cholesterol levels > 240 and 160 mg/dI, respectively and serum triglycerides > 200 mg/dl). It was a 16 week randomised, open-label, parallel design study conducted in our lipid clinic. A 6 week dietary baseline phase was followed by a treatment phase, in which patients received atorvastatin 10 mg/day (n = 45) or micronised fenofibrate 200 mg/day (n = 46) for 16 weeks. Patients were randomly assigned to one of the drugs in sequence orders. Serum lipid profile, including Lp(a), fibrinogen levels, as well as muscle and liver enzymes were measured at screening, at weeks -4, -2, 0 (randomisation) and at 8 and 16 weeks during the treatment period. Atorvastatin was more effective than micronised fenofibrate at lowering total and LDL cholesterol levels, while fenofibrate was more effective at lowering triglycerides and raising HDL cholesterol and ApoAl levels. However, micronised fenofibrate could significantly decrease plasma fibrinogen levels, while atorvastatin evoked a small increase. We conclude that both atorvastatin in small doses and micronised fenofibrate are effective in the improvement of serum lipid profile in patients with mixed hyperlipidemia. However, there are considerable differences between the two drugs concerning their influence on plasma fibrinogen levels.
L. Rallidis, M. Zolindakis 1 . T. Andoniadis, K. Thomaidis, E. Denezos 1, E. Papasteriadis, G. Tsitouris 2. j 1st Department of Cardiology and
Biochemistry Laboratory," General Hospital of Nikea. Piraeus: 22nd Department of CardioloKv; Eoangelismos Hospital. Athens. Greece Introduction: despite the documented benefit of aggressive lipid lowering treatment in secondary prevention of coronary artery disease, several studies have suggested suboptimal lipid management. We aimed to assess how achievable are the targets of lipid lowering treatment in coronary patients in relation to the European (LDL cholesterol < 115 mg/dl) and US (LDL cholesterol < 100 mg/dl) guidelines. Methods: we measured fasting lipids in 2 [6 consecutive patients who attended our outpatient cardiology department. All these patients had suffered a myocardial infarction. Patients with a recent myocardial infarction (<4 months) were excluded. Results: the mean levels of lipids were as follows: total cholesterol = 230 +47 mg/dl, triglycerides = 164+80 mg/dl, LDL cholesterol = 157+35 mg/dl and HDL cholesterol = 38.7±9 mg/dl. Forty-eight (,22.2%) patients were taking a regular hypolipidaemic treatment (30 on statins and the remaining on fibrates or combination of fibrates and statins). In addition, 20 patients had taken only occasionally hypolipidaemic treatment in the past. The table indicates the number of patients with LDL cholesterol < 100 mg/dl, <115 mg/dl and _>130 mg/dl in relation to the regular administration of lipid lowering treatment: Lipid towering treatment
n
Yes No
LDL cholesterol <100 mg/d|
LDL cholesterol
LDL choleslerot >_130 mg/dl
48
I (2A%)
6 (12.5%)
37 {77A%)
168
7 (4.2%)
17 ( 10. 1%)
134 (79.8%)
NS
NS
NS
p
Conclusions: a) a small number of coronary patients requiting lipid lowering treatment is receiving regular hypolipidaemic treatment and b) even those who are treated rarely achieve the lipid goals set by the committees and this underlines the need for more aggressive hypolipidaemic policy.
71st EAS Congress and Satellite Symposia
m
2 C
6 C