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

Per Winkel, Jørgen Hilden, Jørgen Fischer Hansen, Jens Kastrup, Hans Jørn Kolmos, Erik Kjøller, Gorm Boje Jensen, Maria Skoog, Jane Lindschou, Christian Gluud, CLARICOR Trial Group

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 10years follow up.

METHODS: The CLARICOR trial is a randomised, placebo-controlled trial including 4373 patients with stable coronary heart disease. The interventions were 2weeks of clarithromycin 500mg a day versus placebo. 10year 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 10years (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 10years 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 4years, 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.

OriginalsprogEngelsk
TidsskriftInternational Journal of Cardiology
Vol/bind182
Sider (fra-til)459-465
ISSN0167-5273
DOI
StatusUdgivet - 2015

Fingeraftryk

Clarithromycin
Randomized Controlled Trials
Confidence Intervals
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Placebos
Hospital Mortality

Citer dette

Winkel, Per ; Hilden, Jørgen ; Hansen, Jørgen Fischer ; Kastrup, Jens ; Kolmos, Hans Jørn ; Kjøller, Erik ; Jensen, Gorm Boje ; Skoog, Maria ; Lindschou, Jane ; Gluud, Christian ; CLARICOR Trial Group. / Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial. I: International Journal of Cardiology. 2015 ; Bind 182. s. 459-465.
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title = "Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial",
abstract = "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 10years follow up.METHODS: The CLARICOR trial is a randomised, placebo-controlled trial including 4373 patients with stable coronary heart disease. The interventions were 2weeks of clarithromycin 500mg a day versus placebo. 10year 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 10years (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 10years 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 4years, 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.",
author = "Per Winkel and J{\o}rgen Hilden and Hansen, {J{\o}rgen Fischer} and Jens Kastrup and Kolmos, {Hans J{\o}rn} and Erik Kj{\o}ller and Jensen, {Gorm Boje} and Maria Skoog and Jane Lindschou and Christian Gluud and {CLARICOR Trial Group}",
note = "Copyright {\circledC} 2015 Elsevier Ireland Ltd. All rights reserved.",
year = "2015",
doi = "10.1016/j.ijcard.2015.01.020",
language = "English",
volume = "182",
pages = "459--465",
journal = "International Journal of Cardiology",
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Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial. / Winkel, Per; Hilden, Jørgen; Hansen, Jørgen Fischer; Kastrup, Jens; Kolmos, Hans Jørn; Kjøller, Erik; Jensen, Gorm Boje ; Skoog, Maria; Lindschou, Jane; Gluud, Christian; CLARICOR Trial Group.

I: International Journal of Cardiology, Bind 182, 2015, s. 459-465.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Jensen, Gorm Boje

AU - Skoog, Maria

AU - Lindschou, Jane

AU - Gluud, Christian

AU - CLARICOR Trial Group

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

PY - 2015

Y1 - 2015

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 10years follow up.METHODS: The CLARICOR trial is a randomised, placebo-controlled trial including 4373 patients with stable coronary heart disease. The interventions were 2weeks of clarithromycin 500mg a day versus placebo. 10year 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 10years (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 10years 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 4years, 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 10years follow up.METHODS: The CLARICOR trial is a randomised, placebo-controlled trial including 4373 patients with stable coronary heart disease. The interventions were 2weeks of clarithromycin 500mg a day versus placebo. 10year 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 10years (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 10years 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 4years, 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.

U2 - 10.1016/j.ijcard.2015.01.020

DO - 10.1016/j.ijcard.2015.01.020

M3 - Journal article

C2 - 25602299

VL - 182

SP - 459

EP - 465

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -