Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study

Anne Gjesing; Gunnar H Gislason; Stefan B Christensen; Mads E Jørgensen; Charlotte Mérie; Mette Lykke Norgaard; Henrik Enghusen Poulsen; Finn Gustafsson; Lars Køber; Christian Torp-Pedersen; Charlotte Andersson

doi:10.1002/pds.3746

Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study

Anne Gjesing, Gunnar H Gislason, Stefan B Christensen, Mads E Jørgensen, Charlotte Mérie, Mette Lykke Norgaard, Henrik Enghusen Poulsen, Finn Gustafsson, Lars Køber, Christian Torp-Pedersen, Charlotte Andersson

Department of Clinical Medicine

5 Citations (Scopus)

Abstract

Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure. Methods: Through individual-level-linkage of Danish national registries, we identified patients discharged from first-time hospitalization for heart failure in 1997-2010. We estimated the risk of mortality associated with quinine treatment by time-dependent Poisson regression models. Results: A total of 135529 patients were included, with 14510 patients (11%) using quinine at some point. During a median time of follow-up of 989days (interquartile range 350-2004) 88878 patients (66%) died. Patients receiving quinine had slightly increased mortality risk, adjusted incidence rate ratio (IRR) 1.04 (95% confidence interval [CI] 1.01 to 1.07). The risks differed according to concomitant β-blocker treatment. For patients treated with both quinine and β-blockers IRR was 1.15 (95% CI 1.09 to 1.21) vs. 0.99 (95% CI 0.96 to 1.03) for patients treated with quinine but not β-blockers. The risks were highest shortly after initiation of therapy: for the first 14days of treatment IRR was 2.12 (95% CI 1.54 to 2.93) for patients in treatment with β-blockers and 1.17 (95% CI 0.86 to 1.59) for patients not treated with β-blockers. Conclusions: Use of quinine was common and associated with increased mortality in heart failure, especially if administered together with β-blockers and shortly after treatment initiation. Mechanisms underlying the findings remain to be established.

Original language	English
Journal	Pharmacoepidemiology and Drug Safety
Volume	24
Issue number	3
Pages (from-to)	310-8
Number of pages	9
ISSN	1053-8569
DOIs	https://doi.org/10.1002/pds.3746
Publication status	Published - 1 Mar 2015

Keywords

Aged
Aged, 80 and over
Denmark
Female
Follow-Up Studies
Heart Failure
Hospitalization
Humans
Male
Middle Aged
Mortality
Muscle Relaxants, Central
Quinine
Registries
Risk Factors

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Gjesing, A., Gislason, G. H., Christensen, S. B., Jørgensen, M. E., Mérie, C., Norgaard, M. L., Poulsen, H. E., Gustafsson, F., Køber, L., Torp-Pedersen, C., & Andersson, C. (2015). Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study. Pharmacoepidemiology and Drug Safety, 24(3), 310-8. https://doi.org/10.1002/pds.3746

@article{43eda93910c24a3686abe16f9734e1ac,

title = "Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study",

abstract = "Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure. Methods: Through individual-level-linkage of Danish national registries, we identified patients discharged from first-time hospitalization for heart failure in 1997-2010. We estimated the risk of mortality associated with quinine treatment by time-dependent Poisson regression models. Results: A total of 135529 patients were included, with 14510 patients (11%) using quinine at some point. During a median time of follow-up of 989days (interquartile range 350-2004) 88878 patients (66%) died. Patients receiving quinine had slightly increased mortality risk, adjusted incidence rate ratio (IRR) 1.04 (95% confidence interval [CI] 1.01 to 1.07). The risks differed according to concomitant β-blocker treatment. For patients treated with both quinine and β-blockers IRR was 1.15 (95% CI 1.09 to 1.21) vs. 0.99 (95% CI 0.96 to 1.03) for patients treated with quinine but not β-blockers. The risks were highest shortly after initiation of therapy: for the first 14days of treatment IRR was 2.12 (95% CI 1.54 to 2.93) for patients in treatment with β-blockers and 1.17 (95% CI 0.86 to 1.59) for patients not treated with β-blockers. Conclusions: Use of quinine was common and associated with increased mortality in heart failure, especially if administered together with β-blockers and shortly after treatment initiation. Mechanisms underlying the findings remain to be established.",

keywords = "Aged, Aged, 80 and over, Denmark, Female, Follow-Up Studies, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Mortality, Muscle Relaxants, Central, Quinine, Registries, Risk Factors",

author = "Anne Gjesing and Gislason, {Gunnar H} and Christensen, {Stefan B} and J{\o}rgensen, {Mads E} and Charlotte M{\'e}rie and Norgaard, {Mette Lykke} and Poulsen, {Henrik Enghusen} and Finn Gustafsson and Lars K{\o}ber and Christian Torp-Pedersen and Charlotte Andersson",

note = "Copyright {\textcopyright} 2015 John Wiley & Sons, Ltd.",

year = "2015",

month = mar,

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doi = "10.1002/pds.3746",

language = "English",

volume = "24",

pages = "310--8",

journal = "Pharmacoepidemiology and Drug Safety",

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publisher = "JohnWiley & Sons Ltd",

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TY - JOUR

T1 - Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study

AU - Gjesing, Anne

AU - Gislason, Gunnar H

AU - Christensen, Stefan B

AU - Jørgensen, Mads E

AU - Mérie, Charlotte

AU - Norgaard, Mette Lykke

AU - Poulsen, Henrik Enghusen

AU - Gustafsson, Finn

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Andersson, Charlotte

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure. Methods: Through individual-level-linkage of Danish national registries, we identified patients discharged from first-time hospitalization for heart failure in 1997-2010. We estimated the risk of mortality associated with quinine treatment by time-dependent Poisson regression models. Results: A total of 135529 patients were included, with 14510 patients (11%) using quinine at some point. During a median time of follow-up of 989days (interquartile range 350-2004) 88878 patients (66%) died. Patients receiving quinine had slightly increased mortality risk, adjusted incidence rate ratio (IRR) 1.04 (95% confidence interval [CI] 1.01 to 1.07). The risks differed according to concomitant β-blocker treatment. For patients treated with both quinine and β-blockers IRR was 1.15 (95% CI 1.09 to 1.21) vs. 0.99 (95% CI 0.96 to 1.03) for patients treated with quinine but not β-blockers. The risks were highest shortly after initiation of therapy: for the first 14days of treatment IRR was 2.12 (95% CI 1.54 to 2.93) for patients in treatment with β-blockers and 1.17 (95% CI 0.86 to 1.59) for patients not treated with β-blockers. Conclusions: Use of quinine was common and associated with increased mortality in heart failure, especially if administered together with β-blockers and shortly after treatment initiation. Mechanisms underlying the findings remain to be established.

AB - Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure. Methods: Through individual-level-linkage of Danish national registries, we identified patients discharged from first-time hospitalization for heart failure in 1997-2010. We estimated the risk of mortality associated with quinine treatment by time-dependent Poisson regression models. Results: A total of 135529 patients were included, with 14510 patients (11%) using quinine at some point. During a median time of follow-up of 989days (interquartile range 350-2004) 88878 patients (66%) died. Patients receiving quinine had slightly increased mortality risk, adjusted incidence rate ratio (IRR) 1.04 (95% confidence interval [CI] 1.01 to 1.07). The risks differed according to concomitant β-blocker treatment. For patients treated with both quinine and β-blockers IRR was 1.15 (95% CI 1.09 to 1.21) vs. 0.99 (95% CI 0.96 to 1.03) for patients treated with quinine but not β-blockers. The risks were highest shortly after initiation of therapy: for the first 14days of treatment IRR was 2.12 (95% CI 1.54 to 2.93) for patients in treatment with β-blockers and 1.17 (95% CI 0.86 to 1.59) for patients not treated with β-blockers. Conclusions: Use of quinine was common and associated with increased mortality in heart failure, especially if administered together with β-blockers and shortly after treatment initiation. Mechanisms underlying the findings remain to be established.

KW - Aged

KW - Aged, 80 and over

KW - Denmark

KW - Female

KW - Follow-Up Studies

KW - Heart Failure

KW - Hospitalization

KW - Humans

KW - Male

KW - Middle Aged

KW - Mortality

KW - Muscle Relaxants, Central

KW - Quinine

KW - Registries

KW - Risk Factors

U2 - 10.1002/pds.3746

DO - 10.1002/pds.3746

M3 - Journal article

C2 - 25656791

SN - 1053-8569

VL - 24

SP - 310

EP - 318

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

IS - 3

ER -

Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study

Abstract

Keywords

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