Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease

Christel Renoux, Sophie Dell'Aniello, Paul Khairy, Connie Marras, Shawn Bugden, Tanvir Chowdhury Turin, Lucie Blais, Hala Tamim, Charity Evans, Russell Steele, Colin Dormuth, Pierre Ernst, Samy Suissa, Colin R. Dormuth, Brenda R. Hemmelgarn, Gary F. Teare, Patricia Caetano, J. Michael Paterson, Jacques LeLorier, Adrian R. Levy & 4 others Pierre Ernst, Robert W. Platt, Ingrid S. Sketris, Canadian Network of Observational Drug Effect Studies (CNODES)

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13 Citations (Scopus)

Abstract

Aim: Domperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown. Methods: We conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case–control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly-diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta-analytic methods were used to estimate overall effects across sites. Results: Among 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person-years of follow-up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non-statistically significant 22% increased risk of VT/SCD (RR 1.22; 95% CI 0.99–1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95% CI 1.07–1.78), but not in those without (RR 1.21; 95% CI 0.81–1.81). Dose and duration of use did not affect the magnitude of the risk. Conclusion: Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.

Original languageEnglish
Pages (from-to)461-472
Number of pages12
JournalBritish Journal of Clinical Pharmacology
Volume82
Issue number2
DOIs
Publication statusPublished - 1 Aug 2016
Externally publishedYes

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Domperidone
Sudden Cardiac Death
Tachycardia
Parkinson Disease
Cardiovascular Diseases
Vital Statistics
Antiemetics
Medical Records
Cohort Studies
Retrospective Studies
Databases
Mortality
Incidence
Research

Cite this

Renoux, C., Dell'Aniello, S., Khairy, P., Marras, C., Bugden, S., Turin, T. C., ... Canadian Network of Observational Drug Effect Studies (CNODES) (2016). Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease. British Journal of Clinical Pharmacology, 82(2), 461-472. https://doi.org/10.1111/bcp.12964
Renoux, Christel ; Dell'Aniello, Sophie ; Khairy, Paul ; Marras, Connie ; Bugden, Shawn ; Turin, Tanvir Chowdhury ; Blais, Lucie ; Tamim, Hala ; Evans, Charity ; Steele, Russell ; Dormuth, Colin ; Ernst, Pierre ; Suissa, Samy ; Dormuth, Colin R. ; Hemmelgarn, Brenda R. ; Teare, Gary F. ; Caetano, Patricia ; Michael Paterson, J. ; LeLorier, Jacques ; Levy, Adrian R. ; Ernst, Pierre ; Platt, Robert W. ; Sketris, Ingrid S. ; Canadian Network of Observational Drug Effect Studies (CNODES). / Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease. In: British Journal of Clinical Pharmacology. 2016 ; Vol. 82, No. 2. pp. 461-472.
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title = "Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease",
abstract = "Aim: Domperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown. Methods: We conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case–control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly-diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta-analytic methods were used to estimate overall effects across sites. Results: Among 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person-years of follow-up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non-statistically significant 22{\%} increased risk of VT/SCD (RR 1.22; 95{\%} CI 0.99–1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95{\%} CI 1.07–1.78), but not in those without (RR 1.21; 95{\%} CI 0.81–1.81). Dose and duration of use did not affect the magnitude of the risk. Conclusion: Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.",
author = "Christel Renoux and Sophie Dell'Aniello and Paul Khairy and Connie Marras and Shawn Bugden and Turin, {Tanvir Chowdhury} and Lucie Blais and Hala Tamim and Charity Evans and Russell Steele and Colin Dormuth and Pierre Ernst and Samy Suissa and Dormuth, {Colin R.} and Hemmelgarn, {Brenda R.} and Teare, {Gary F.} and Patricia Caetano and {Michael Paterson}, J. and Jacques LeLorier and Levy, {Adrian R.} and Pierre Ernst and Platt, {Robert W.} and Sketris, {Ingrid S.} and {Canadian Network of Observational Drug Effect Studies (CNODES)}",
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Renoux, C, Dell'Aniello, S, Khairy, P, Marras, C, Bugden, S, Turin, TC, Blais, L, Tamim, H, Evans, C, Steele, R, Dormuth, C, Ernst, P, Suissa, S, Dormuth, CR, Hemmelgarn, BR, Teare, GF, Caetano, P, Michael Paterson, J, LeLorier, J, Levy, AR, Ernst, P, Platt, RW, Sketris, IS & Canadian Network of Observational Drug Effect Studies (CNODES) 2016, 'Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease' British Journal of Clinical Pharmacology, vol. 82, no. 2, pp. 461-472. https://doi.org/10.1111/bcp.12964

Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease. / Renoux, Christel; Dell'Aniello, Sophie; Khairy, Paul; Marras, Connie; Bugden, Shawn; Turin, Tanvir Chowdhury; Blais, Lucie; Tamim, Hala; Evans, Charity; Steele, Russell; Dormuth, Colin; Ernst, Pierre; Suissa, Samy; Dormuth, Colin R.; Hemmelgarn, Brenda R.; Teare, Gary F.; Caetano, Patricia; Michael Paterson, J.; LeLorier, Jacques; Levy, Adrian R.; Ernst, Pierre; Platt, Robert W.; Sketris, Ingrid S.; Canadian Network of Observational Drug Effect Studies (CNODES).

In: British Journal of Clinical Pharmacology, Vol. 82, No. 2, 01.08.2016, p. 461-472.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease

AU - Renoux, Christel

AU - Dell'Aniello, Sophie

AU - Khairy, Paul

AU - Marras, Connie

AU - Bugden, Shawn

AU - Turin, Tanvir Chowdhury

AU - Blais, Lucie

AU - Tamim, Hala

AU - Evans, Charity

AU - Steele, Russell

AU - Dormuth, Colin

AU - Ernst, Pierre

AU - Suissa, Samy

AU - Dormuth, Colin R.

AU - Hemmelgarn, Brenda R.

AU - Teare, Gary F.

AU - Caetano, Patricia

AU - Michael Paterson, J.

AU - LeLorier, Jacques

AU - Levy, Adrian R.

AU - Ernst, Pierre

AU - Platt, Robert W.

AU - Sketris, Ingrid S.

AU - Canadian Network of Observational Drug Effect Studies (CNODES)

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Aim: Domperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown. Methods: We conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case–control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly-diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta-analytic methods were used to estimate overall effects across sites. Results: Among 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person-years of follow-up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non-statistically significant 22% increased risk of VT/SCD (RR 1.22; 95% CI 0.99–1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95% CI 1.07–1.78), but not in those without (RR 1.21; 95% CI 0.81–1.81). Dose and duration of use did not affect the magnitude of the risk. Conclusion: Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.

AB - Aim: Domperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown. Methods: We conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case–control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly-diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta-analytic methods were used to estimate overall effects across sites. Results: Among 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person-years of follow-up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non-statistically significant 22% increased risk of VT/SCD (RR 1.22; 95% CI 0.99–1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95% CI 1.07–1.78), but not in those without (RR 1.21; 95% CI 0.81–1.81). Dose and duration of use did not affect the magnitude of the risk. Conclusion: Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.

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U2 - 10.1111/bcp.12964

DO - 10.1111/bcp.12964

M3 - Article

VL - 82

SP - 461

EP - 472

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

SN - 0306-5251

IS - 2

ER -