The Risk of Ischaemic Stroke during the Fluvastatine and Fenofibrate Treatment

Czech version

Authors: D. Školoudík ¹; M. Bar ¹; D. Václavík ²; O. Škoda ³; J. Korsa ⁴; P. Hradílek ¹; K. Šimíčková ¹; V. Kosek ⁵; V. Ploticová ⁶; K. Urbancová ⁷; R. Herzig ⁸; P. Kaňovský ⁸
Authors‘ workplace: Neurologická klinika ¹; Neurologické oddělení ²; Neurologické oddělení, Nemocnice Pelhřimov ³; Neurologická klinika, FN Královské Vinohrady, Praha ⁴; Oddělení informatiky ⁵; Lipologická ambulance, FNsP Ostrava-Poruba, Ostrava ⁶; Lipologická ambulance, Vítkovická nemocnice, Ostrava ⁷; Neurologická klinika, FN a LF, Olomouc ⁸
Published in: Cesk Slov Neurol N 2007; 70/103(2): 163-167
Category: Original Paper

Overview

Introduction:
A neurological ultrasound study is an open, randomized multicentric trial realized in 4 neurosonological centres in the Czech Republic. A secondary aim of the study was to find out differences in the number of vascular accidents occurring in the course of therapy with fluvastatine and phenofibrate.

Methods:
Totally 376 patients with neurological symptoms, atherosclerotic plate in the carotid bifurcation over 2.0 mm (mean 3.05 mm) and the total level of cholesterol over 5.0 mmol*l^-1 (mean 6.54 mmol*l^-1) were randomized into two therapeutical branches – fluvastatine 40 mg and phenofibrate 200 mg. The patients were followed up ultrasonographically and clinically every 3 months for 2 years.

Results:
The number of vascular accidents was statistically insignificantly lower in a group of phenofibrate – 29 accidents in 24 patients vs 36 accidents in 31 patients in a fluvastatine group. The risk of vascular accidents was significantly higher in patients after a transitory ischemic attack or cerebrovascular accident, in patients with an initially wider atherosclerotic plate, lower level of HDL-cholesterol or its smaller increase in the course of studying, higher level of triglycerides or smaller reduction of their levels during follow-up, and higher ratio of LDL/HDL cholesterol.

Conclusion:
Although the results of NUS study have confirmed better effects of fluvastatine if compared with phenofibrate on slowing down the progression of an atherosclerotic plate in the carotid bifurcation, there was demonstrated no difference in the total numnber of vascular accidents during the first two years of treatment.

Key words:
fluvastatine, phenofibrate, vascular accident, cholesterol

Sources

1. The 4S study group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-9.

2. Kjekshus J, Pedersen TR. Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 1995; 76: C64-8.

3. Goldberg RB, Mellies MJ, Sacks FM, Moye LA, Howard BV, Davis BR et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analysis in the Cholesterol and Recurrent Event (CARE) Trial. Circulation 1998; 98: 2513-9.

4. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001-9.

5. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615-2.

6. Češka R (Ed). Cholesterol a ateroskleróza. Praha: Maxdorf 1999: 9-23.

7. Widimský J (Ed). Léčba dyslipidemií a ICHS. Praha: Triton 1998: 11-202.

8. The long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349-57.

9. Rizos E, Mikhailidis DP. Are high-density lipoprotein and triglyceride levels important in secondary prevention: impressions from the BIP and VA-HIT trials. Int J Cardiol 2002; 82: 199-207.

10. Robins SJ, Collins D, Witters JT, Papademetriou V, Deedwania PC, Schaefer EJ et al. Relation of gemfibrosil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001; 285: 1585-91.

11. Bloomfield Rubins H, Davenport J, Babikian V, Brass LM, Collins D, Wexler L et al. Reduction in stroke with gemfibrosil in men with coronary heart disease and low HDL cholesterol. The Veterans Affair HDL Intervention Trial (VA-HIT). Circulation 2001; 285: 1585-91.

12. Ericsson CG, Nilsson J, Grip L, Svane B, Hamsten A. Effect of bezafibrate treatment over five years on coronary plaques causing 20% to 50% diameter narrowing. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT). Am J Cardiol 1997; 80: 1125-9.

13. The BIP Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. The Bezafibrate Infarction Prevention (BIP) Study. Circulation 2000; 102: 21-7.

14. A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Report from the Committee of Principal Investigators. Br Heart J 1978; 40: 1069-118.

15. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB et al. Gemfibrosil for the secondary prevention of coronary heart disease in men with low levels of high density lipoprotein cholesterol. N Engl J Med 1999; 341: 410-8.

16. Robins JS. Cardiovascular disease in patients with diabetes or metabolic syndrome: statins or fibrates? Cur Op Lipid 2003; 14: 575-83.

17. Školoudík D, Bar M, Václavík D, Škoda O, Korsa J, Hradílek P et al. Neurologická ultrazvuková studie - design studie. Neuro3 2004; 03: A01. Available from: URL: www.neuro3.cz

18. Školoudík D, Bar M, Václavík D, Škoda O, Korsa J, Hradílek P et al. Ovlivnění progrese pokročilé aterosklerózy v karotické bifurkaci a rizika vaskulárních příhod léčbou fluvastatinem a fenofibrátem – výsledky Neurologické ultrazvukové studie (NUS). Cor et Vasa 2005; 47: 147-55.

19. Knopp RH, Brown WV, Dujovne CA, Farquhar JW, Feldman EB, Goldberg AC et al. Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia. Am J Med 1987; 83: 50-9.

20. Stejskal D. Ateroskleróza – etiopatogeneze, diagnostika a léčba. Praha: BMS 1999: 21-203.

21. Heart Protection Study Collaborative Group. MRC/BHFHeart Protection Study of cholesterol lowering with simvastatin in men and 20536 high-risk individuals: a randomized placebo controlled trial. Lancet 2002; 360: 7-22.

22. ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care. The Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002; 288: 2998-3007.

23. Kalvach P (Ed). Mozkové ischémie a hemoragie. 2. ed. Praha: Grada 2000.

24. Thompson GR, Wilson PW (Eds). Coronary risk factors and their assessment. London: Science Press 1992.

25. Steinberg D, Witzum JL. Lipoproteins and atherosclerosis. Current concepts. JAMA 1990; 264: 3047-52.