title: Statin treatment prevents increased cardiovascular and all-cause mortality associated with clarithromycin in patients with stable coronary heart disease.
abstract: 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.
authors.affiliation: Department of Cardiology, Hvidovre Hospital, Copenhagen University Hospital, Denmark.
authors.forename: Gorm B
authors.initials: GB
authors.lastname: Jensen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Hilden
authors.forename: Bodil
authors.initials: B
authors.lastname: Als-Nielsen
authors.forename: Morten
authors.initials: M
authors.lastname: Damgaard
authors.forename: Jørgen Fischer
authors.initials: JF
authors.lastname: Hansen
authors.forename: Stig
authors.initials: S
authors.lastname: Hansen
authors.forename: Olav H
authors.initials: OH
authors.lastname: Helø
authors.forename: Per
authors.initials: P
authors.lastname: Hildebrandt
authors.forename: Jens
authors.initials: J
authors.lastname: Kastrup
authors.forename: Hans Jørn
authors.initials: HJ
authors.lastname: Kolmos
authors.forename: Erik
authors.initials: E
authors.lastname: Kjøller
authors.forename: Inga
authors.initials: I
authors.lastname: Lind
authors.forename: Henrik
authors.initials: H
authors.lastname: Nielsen
authors.forename: Lars
authors.initials: L
authors.lastname: Petersen
authors.forename: Christian M
authors.initials: CM
authors.lastname: Jespersen
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
mesh_terms: 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
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017291:Clarithromycin