Beneficial effect of clarithromycin in patients with acute coronary syndrome and complement C4 deficiencies.
OBJECTIVE
We sought to examine the role of complement component C4 deficiencies on the effect of antibiotic treatment in patients with acute coronary syndrome (ACS).


METHODS
Patients with ACS (n=144) were randomly divided to receive a three-month treatment of clarithromycin or placebo and followed for major adverse coronary and cerebrovascular events (MACCEs) for 404.5 median days (range 138-924 days). The primary results indicated that clarithromycin prevented recurrent cardiovascular attacks. For the present study we performed serum C4 allotyping of C4A and C4B. The clarithromycin response was reanalyzed taking into account the deficiencies in the C4 allotypes.


RESULTS
The prevalence of C4A deficiency, C4B deficiency or these combined were 29.2% (42/144), 39.6% (57/144) and 66.0% (95/144), respectively. In patients with C4 deficiencies clarithromycin treatment resulted in a reduced number of MACCEs and the best cumulative survival as compared with the placebo group (MACCE 18.8% versus 39.1%, respectively; Log rank test, p=0.015).


CONCLUSIONS
Only patients with ACS and C4 deficiencies seem to benefit from antibiotic treatment. This may explain the controversial results of secondary prevention trials of coronary artery disease and possibly serve as a pharmacogenomic marker for clarithromycin treatment.
Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Riitta
R
Paakkanen
Anil
A
Palikhe
Mikko
M
Seppänen
Markku S
MS
Nieminen
Hanna
H
Vauhkonen
Pekka
P
Saikku
Marja-Liisa
ML
Lokki
Juha
J
Sinisalo
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification; D017291:Clarithromycin / Q000627:therapeutic use*; D003181:Complement C4 / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000900:Anti-Bacterial Agents; D003181:Complement C4; D017291:Clarithromycin