Statin treatment prevents increased cardiovascular and all-cause mortality associated with clarithromycin in patients with stable coronary heart disease.
In the CLARICOR trial, significantly increased cardiovascular (CV) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin. We report on the impact of statin treatment at entry on the CV and all-cause mortality. The multicenter CLARICOR trial randomized patients to oral clarithromycin (500 mg daily; n = 2172) versus matching placebo (daily; n = 2201) for 2 weeks. Patients were followed through public databases. In the 41% patients on statin treatment at entry, no significant effect of clarithromycin was observed on CV (hazard ratio [HR], 0.68, 95% confidence interval [CI], 0.38-1.22; P = 0.20) or all-cause mortality (HR, 1.08; 95% CI, 0.71-1.65; P = 0.72) at 2.6-year follow up. In the patients not on statin treatment at entry, clarithromycin was associated with a significant increase in CV (HR, 1.90; 95% CI, 1.34-2.67; P = 0.0003; statin-clarithromycin interaction P = 0.0029) and all-cause mortality (HR, 1.33; 95% CI, 1.05-1.67; P = 0.016; statin-clarithromycin interaction P = 0.41). Multivariate analysis and 6-year follow up confirmed these results. Concomitant statin treatment in stable patients with coronary heart disease abrogated the observed increased CV mortality associated with 2 weeks of clarithromycin.
Jensen
Gorm B
GB
Department of Cardiology, Hvidovre Hospital, Copenhagen University Hospital, Denmark.
Hilden
Jørgen
J
Als-Nielsen
Bodil
B
Damgaard
Morten
M
Hansen
Jørgen Fischer
JF
Hansen
Stig
S
Helø
Olav H
OH
Hildebrandt
Per
P
Kastrup
Jens
J
Kolmos
Hans Jørn
HJ
Kjøller
Erik
E
Lind
Inga
I
Nielsen
Henrik
H
Petersen
Lars
L
Jespersen
Christian M
CM
Gluud
Christian
C
D000368:Aged; D017291:Clarithromycin / Q000009:adverse effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017291:Clarithromycin