Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial).
BACKGROUND
Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS.


METHODS
The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy.


RESULTS
We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037).


CONCLUSIONS
This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.


BACKGROUND
NCT00171275.
Ostadal
Petr
P
Heart Center, Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic. ostadal@yahoo.com
Alan
David
D
Vejvoda
Jiri
J
Kukacka
Jiri
J
Macek
Milan
M
Hajek
Petr
P
Mates
Martin
M
Kvapil
Milan
M
Kettner
Jiri
J
Wiendl
Martin
M
Aschermann
Ondrej
O
Slaby
Josef
J
Holm
Frantisek
F
Telekes
Peter
P
Horak
David
D
Blasko
Peter
P
Zemanek
David
D
Veselka
Josef
J
Cepova
Jana
J
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D018153:Czech Republic; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010343:Patient Admission; D018579:Patient Selection; D015990:Placebo Effect; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011446:Prospective Studies; D018570:Risk Assessment; D018401:Sample Size; D055502:Secondary Prevention / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508600:IL6 protein, human; D007211:Indoles; D018836:Inflammation Mediators; D015850:Interleukin-6; D000077340:Fluvastatin; D002097:C-Reactive Protein; D011266:Pregnancy-Associated Plasma Protein-A