BMJ  2006;332:22-27 (7 January), doi:10.1136/bmj.38666.653600.55 (published 8 December 2005)

Research

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

¹ Bispebjerg Hospital, Copenhagen University Hospital, Department of Cardiology Y, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark, ² Amager Hospital, Copenhagen University Hospital, Department of Cardiology, DK-2300 Copenhagen, ³ Hvidovre Hospital, Copenhagen University Hospital, Department of Cardiology, DK-2650 Hvidovre, Denmark, ⁴ Rigshospitalet, Copenhagen University Hospital, The Heart Centre, Department of Medicine B, DK-2100 Copenhagen, ⁵ Frederiksberg Hospital, Copenhagen University Hospital, Department of Cardiology E, DK-2000 Frederiksberg, Denmark, ⁶ Department of Biostatistics, Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, ⁷ Department of Clinical Microbiology, Odense University Hospital, DK-5000 Odense, Denmark, ⁸ Statens Serum Institut, DK-2300 Copenhagen, ⁹ Herlev Hospital, Copenhagen University Hospital, Department of Cardiology S, DK-2730 Herlev, Denmark, ¹⁰ The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Institute of Preventive Medicine and Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen

Abstract

Objective To determine if the macrolide clarithromycin affects mortality and cardiovascular morbidity in patients with stable coronary heart disease.

Design Centrally randomised multicentre trial. All parties at all stages were blinded. Analyses were by intention to treat.

Setting Five Copenhagen University cardiology departments and a coordinating centre.

Participants 13 702 patients aged 18 to 85 years who had a discharge diagnosis of myocardial infarction or angina pectoris in 1993-9 and alive in August 1999 were invited by letter; 4373 were randomised.

Interventions Two weeks' treatment with clarithromycin 500 mg/day or matching placebo.

Main outcome measures Primary outcome: composite of all cause mortality, myocardial infarction, or unstable angina pectoris during three years' follow-up. Secondary outcome: composite of cardiovascular mortality, myocardial infarction, or unstable angina pectoris. The outcomes were obtained from Danish registers and were blindly assessed by the event committee.

Results 2172 participants were randomised to clarithromycin and 2201 to placebo. We found no significant effects of clarithromycin on the primary outcome (hazard ratio 1.15, 95% confidence interval 0.99 to 1.34) or secondary outcome (1.17, 0.98 to 1.40). Mortality was significantly higher in the clarithromycin arm (1.27, 1.03 to 1.54; P = 0.03) as a result of significantly higher cardiovascular mortality (1.45, 1.09 to 1.92; P = 0.01).

Conclusions Short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality. The long term safety of clarithromycin in patients with stable ischaemic heart disease should be examined.

Trial registration ClinicalTrials.gov NCT00121550 [ClinicalTrials.gov] .

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