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Beneficial effect of clarithromycin in patients with acute coronary syndrome and complement C4 deficiencies

Riitta Paakkanen1, Anil Palikhe, Mikko Seppänen

  • 1Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.

Scandinavian Cardiovascular Journal : SCJ
|April 15, 2009
PubMed

Insights

Complement component C4 deficiencies in acute coronary syndrome (ACS) patients indicate benefit from clarithromycin antibiotic treatment. This finding may explain varied trial outcomes and serve as a pharmacogenomic marker.

Area of Science:

  • Cardiology
  • Immunology
  • Pharmacogenomics

Background:

  • Acute coronary syndrome (ACS) treatment outcomes can be variable.
  • The role of complement component C4 deficiencies in cardiovascular disease is not fully understood.
  • Antibiotic treatments have shown controversial results in secondary prevention trials for coronary artery disease.

Purpose of the Study:

  • To investigate the influence of complement component C4 deficiencies on the efficacy of antibiotic treatment in ACS patients.
  • To determine if C4 allotypes can predict response to clarithromycin therapy in ACS.

Main Methods:

  • 144 ACS patients were randomized to receive clarithromycin or placebo for three months.
  • Serum C4 allotyping (C4A and C4B) was performed.
  • Treatment response was reanalyzed based on the presence or absence of C4 deficiencies.

Main Results:

  • The prevalence of C4A and C4B deficiencies was significant in the study population (29.2% and 39.6%, respectively).
  • In patients with C4 deficiencies, clarithromycin treatment significantly reduced major adverse coronary and cerebrovascular events (MACCEs) compared to placebo (18.8% vs. 39.1%).
  • Clarithromycin treatment in C4-deficient patients led to better cumulative survival.

Conclusions:

  • Only ACS patients with complement component C4 deficiencies appear to benefit from clarithromycin treatment.
  • C4 deficiencies may explain inconsistent results in secondary prevention trials for coronary artery disease.
  • C4 allotyping could serve as a pharmacogenomic marker for predicting clarithromycin efficacy in ACS patients.
Abstract

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