Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial

TY - JOUR

T1 - Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial

AU - Winkel, Per

AU - Hilden, Jørgen

AU - Hansen, Jørgen Fischer

AU - Kastrup, Jens

AU - Kolmos, Hans Jørn

AU - Kjøller, Erik

AU - Boje Jensen, Gorm

AU - Skoog, Maria

AU - Lindschou, Jane

AU - Gluud, Christian

AU - CLARICOR Trial Group

N1 - Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Background The CLARICOR trial reported that clarithromycin compared with placebo increased all-cause mortality in patients with stable coronary heart disease. This study investigates the effects of clarithromycin versus placebo during 10 years follow up. Methods The CLARICOR trial is a randomised, placebo-controlled trial including 4373 patients with stable coronary heart disease. The interventions were 2 weeks of clarithromycin 500 mg a day versus placebo. 10 year follow up was performed through Danish public registers and analysed with Cox regression. Results Clarithromycin increased all-cause mortality (hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.00-1.21) and cerebrovascular disease during 10 years (HR: 1.19, 95% CI: 1.02-1.38). The increased mortality and morbidity were restricted to patients not on statin at entry (HR: 1.16, 95% CI: 1.04-1.31, and HR: 1.25, 95% CI: 1.03-1.50). The assumption of constant HR during the 10 years was violated for cardiovascular death (P = 0.01) and cardiovascular death outside hospital (P < 0.0005). Analyses of the effects over time showed that clarithromycin increased cardiovascular mortality during the first three years (HR: 1.42, 95% CI: 1.09-1.84) due to increased cardiovascular mortality outside hospital in patients not on statin (HR: 2.36, 95% CI: 1.60-3.50). During the last 4 years, cardiovascular death outside hospital was lower in the clarithromycin group (HR: 0.64, 95% CI: 0.46-0.88). Conclusion Clarithromycin increased mortality due to cardiovascular death outside hospital and cerebrovascular morbidity in patients with stable coronary heart disease who were not on statin. The increased cardiovascular mortality was years later compensated, likely through frailty attrition.

AB - Background The CLARICOR trial reported that clarithromycin compared with placebo increased all-cause mortality in patients with stable coronary heart disease. This study investigates the effects of clarithromycin versus placebo during 10 years follow up. Methods The CLARICOR trial is a randomised, placebo-controlled trial including 4373 patients with stable coronary heart disease. The interventions were 2 weeks of clarithromycin 500 mg a day versus placebo. 10 year follow up was performed through Danish public registers and analysed with Cox regression. Results Clarithromycin increased all-cause mortality (hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.00-1.21) and cerebrovascular disease during 10 years (HR: 1.19, 95% CI: 1.02-1.38). The increased mortality and morbidity were restricted to patients not on statin at entry (HR: 1.16, 95% CI: 1.04-1.31, and HR: 1.25, 95% CI: 1.03-1.50). The assumption of constant HR during the 10 years was violated for cardiovascular death (P = 0.01) and cardiovascular death outside hospital (P < 0.0005). Analyses of the effects over time showed that clarithromycin increased cardiovascular mortality during the first three years (HR: 1.42, 95% CI: 1.09-1.84) due to increased cardiovascular mortality outside hospital in patients not on statin (HR: 2.36, 95% CI: 1.60-3.50). During the last 4 years, cardiovascular death outside hospital was lower in the clarithromycin group (HR: 0.64, 95% CI: 0.46-0.88). Conclusion Clarithromycin increased mortality due to cardiovascular death outside hospital and cerebrovascular morbidity in patients with stable coronary heart disease who were not on statin. The increased cardiovascular mortality was years later compensated, likely through frailty attrition.

KW - Aged

KW - Anti-Bacterial Agents

KW - Cause of Death

KW - Clarithromycin

KW - Coronary Artery Disease

KW - Denmark

KW - Female

KW - Follow-Up Studies

KW - Forecasting

KW - Humans

KW - Male

KW - Morbidity

KW - Retrospective Studies

KW - Single-Blind Method

KW - Stroke

U2 - 10.1016/j.ijcard.2015.01.020

DO - 10.1016/j.ijcard.2015.01.020

M3 - Journal article

C2 - 25602299

SN - 0167-5273

VL - 182

SP - 459

EP - 465

JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -