Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial

Jespersen and colleagues (1) examined the effect of Clarithromycin
treatment in patients with stable coronary heart disease (CHD).
Clarithromycin was associated with increased cardiovascular mortality.
There appeared to be no beneficial effects of antibiotic therapy in CHD
patients infected with Chlamydia pneumoniae.

Although not entirely explicit, the authors’ postulated pre-hoc, any
improvement in cardiovascular mortality may be secondary to eradication or
suppression of C pneumoniae infection. However, evidence of infection was
not necessary for patient inclusion. Accordingly, the frequency of
infection in treatment and placebo arms was unknown.

Post-hoc, C pneumoniae IgG antibodies were found in approximately 60%
of each group and IgA antibodies in 20%. Antibody measurements were not
effected by treatment but this is not surprising because elevated single
specimen IgG titres usually represent past exposure to C pneumoniae. IgA
antibodies may be a better surrogate marker of chronic infection but this
is not certain (2). In general, serological measurements are not
recommended for the diagnosis of chronic C pneumoniae infection (2).

Several large double-blinded placebo controlled antibiotic trials
have attempted to clarify the role of C pneumoniae in CHD with conflicting
results (3). Only a few trials have used evidence of C pneumoniae
infection as inclusion criteria (and these were dependent on antibody
measurements). If the actual percentage of infected patients is small, any
treatment effect will be obscured by the CHD population examined, at
large.

Like Jespersen et al (1), most of these trials and subsequent meta-
analyses, determined that antibiotic treatment of all CHD patients is not
beneficial and in the main, not harmful (3). Now it is necessary to
determine whether CHD patients with C pneumoniae infection may benefit, as
a sub-cohort, from antibiotic treatment. Serum antigen specific methods to
detect C pneumoniae infection are available (4) and should be used to
screen future populations for inclusion in placebo controlled trials.

1. Jespersen CM, Als-Nielsen B, Damgaard M, Hansen JF, Hansen S, Helo
OH, et al. Randomised placebo controlled multicentre trial to assess short
term clarithromycin for patients with stable coronary heart disease:
CLARICOR trial. BMJ 2006;332:22-7.

2. Dowell SF, Peeling RW, Boman J, Carlone GM, Fields BS, Guarner J
et al. Standardizing Chlamydia pneumoniae Assays: Recommendations from the
Centers for Disease Control and Prevention (USA) and the Laboratory Center
for Disease Control (Canada). Clin Infect Dis 2001;33:492-503.

3. Andraws R, Berger JS, Brown DL. Effect of Antibiotic Therapy on
Outcomes of Patients With Coronary Artery Disease. A Meta-analysis of
Randomized Controlled Trials. JAMA 2005; 293:2641-2647.

4. Tavendale R, Parratt D, Pringle SD, A'brook R, Tunstall-Pedoe
H.Serological markers of Chlamydia pneumoniae infection in men and women
and subsequent coronary events; the Scottish
Heart Health Study. Eur Heart J. 2002 Feb;23(4):301-7.

Competing interests:
None declared