Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study

INTRODUCTION: The serotonin 5-HT(4) receptor agonist prucalopride is approved in the European Union for the treatment of chronic constipation. This offered the unique opportunity to include real-world observational data on cardiovascular safety in the new drug application for approval of prucaloprid...

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Autores principales: Gilsenan, Alicia, Fortuny, Joan, Cainzos-Achirica, Miguel, Cantero, Oscar F., Flynn, Robert W. V., Garcia-Rodriguez, Luis, Harding, Abenah, Kollhorst, Bianca, Karlsson, Pär, Linnér, Love, MacDonald, Thomas M., Odsbu, Ingvild, Plana, Estel, Ruigómez, Ana, Schink, Tania, Ziemiecki, Ryan, Andrews, Elizabeth B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739451/
https://www.ncbi.nlm.nih.gov/pubmed/31134512
http://dx.doi.org/10.1007/s40264-019-00835-0
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author Gilsenan, Alicia
Fortuny, Joan
Cainzos-Achirica, Miguel
Cantero, Oscar F.
Flynn, Robert W. V.
Garcia-Rodriguez, Luis
Harding, Abenah
Kollhorst, Bianca
Karlsson, Pär
Linnér, Love
MacDonald, Thomas M.
Odsbu, Ingvild
Plana, Estel
Ruigómez, Ana
Schink, Tania
Ziemiecki, Ryan
Andrews, Elizabeth B.
author_facet Gilsenan, Alicia
Fortuny, Joan
Cainzos-Achirica, Miguel
Cantero, Oscar F.
Flynn, Robert W. V.
Garcia-Rodriguez, Luis
Harding, Abenah
Kollhorst, Bianca
Karlsson, Pär
Linnér, Love
MacDonald, Thomas M.
Odsbu, Ingvild
Plana, Estel
Ruigómez, Ana
Schink, Tania
Ziemiecki, Ryan
Andrews, Elizabeth B.
author_sort Gilsenan, Alicia
collection PubMed
description INTRODUCTION: The serotonin 5-HT(4) receptor agonist prucalopride is approved in the European Union for the treatment of chronic constipation. This offered the unique opportunity to include real-world observational data on cardiovascular safety in the new drug application for approval of prucalopride in the USA. METHODS: This observational population-based cohort study (EUPAS9200) conducted in five data sources (three in the UK, one in Sweden, and one in Germany [which was subsequently excluded from the pooled analyses]) aimed to estimate the pooled adjusted incidence rate ratio for major adverse cardiovascular events (defined as hospitalization for non-fatal acute myocardial infarction or stroke, and in-hospital cardiovascular death) in adult initiators of prucalopride compared with initiators of polyethylene glycol 3350 (PEG) following a common protocol. Standardized incidence rates and incidence rate ratios of major adverse cardiovascular events were derived using propensity score stratification. Sensitivity analyses explored the impact of exposure definition, outcome categories, interim cancer, and unmeasured confounding. RESULTS: The pooled analyses included 5715 initiators of prucalopride and 29,372 initiators of PEG. Average duration of use was 175 days for prucalopride and 82 days for PEG. The pooled standardized incidence rate per 1000 person-years (95% confidence interval) of major adverse cardiovascular events was 6.57 (3.90–10.39) for patients initiating prucalopride and 10.24 (6.97–14.13) for PEG. The pooled adjusted incidence rate ratio for major adverse cardiovascular events was 0.64 (95% confidence interval 0.36–1.14). Results remained consistent in various sensitivity analyses. CONCLUSIONS: The pooled incidence rate ratio estimate was consistent with no indication of an increased risk above the pre-specified safety threshold of 3.00 for major adverse cardiovascular events in patients with chronic constipation using prucalopride as compared with PEG.
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spelling pubmed-67394512019-09-25 Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study Gilsenan, Alicia Fortuny, Joan Cainzos-Achirica, Miguel Cantero, Oscar F. Flynn, Robert W. V. Garcia-Rodriguez, Luis Harding, Abenah Kollhorst, Bianca Karlsson, Pär Linnér, Love MacDonald, Thomas M. Odsbu, Ingvild Plana, Estel Ruigómez, Ana Schink, Tania Ziemiecki, Ryan Andrews, Elizabeth B. Drug Saf Original Research Article INTRODUCTION: The serotonin 5-HT(4) receptor agonist prucalopride is approved in the European Union for the treatment of chronic constipation. This offered the unique opportunity to include real-world observational data on cardiovascular safety in the new drug application for approval of prucalopride in the USA. METHODS: This observational population-based cohort study (EUPAS9200) conducted in five data sources (three in the UK, one in Sweden, and one in Germany [which was subsequently excluded from the pooled analyses]) aimed to estimate the pooled adjusted incidence rate ratio for major adverse cardiovascular events (defined as hospitalization for non-fatal acute myocardial infarction or stroke, and in-hospital cardiovascular death) in adult initiators of prucalopride compared with initiators of polyethylene glycol 3350 (PEG) following a common protocol. Standardized incidence rates and incidence rate ratios of major adverse cardiovascular events were derived using propensity score stratification. Sensitivity analyses explored the impact of exposure definition, outcome categories, interim cancer, and unmeasured confounding. RESULTS: The pooled analyses included 5715 initiators of prucalopride and 29,372 initiators of PEG. Average duration of use was 175 days for prucalopride and 82 days for PEG. The pooled standardized incidence rate per 1000 person-years (95% confidence interval) of major adverse cardiovascular events was 6.57 (3.90–10.39) for patients initiating prucalopride and 10.24 (6.97–14.13) for PEG. The pooled adjusted incidence rate ratio for major adverse cardiovascular events was 0.64 (95% confidence interval 0.36–1.14). Results remained consistent in various sensitivity analyses. CONCLUSIONS: The pooled incidence rate ratio estimate was consistent with no indication of an increased risk above the pre-specified safety threshold of 3.00 for major adverse cardiovascular events in patients with chronic constipation using prucalopride as compared with PEG. Springer International Publishing 2019-05-27 2019 /pmc/articles/PMC6739451/ /pubmed/31134512 http://dx.doi.org/10.1007/s40264-019-00835-0 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research Article
Gilsenan, Alicia
Fortuny, Joan
Cainzos-Achirica, Miguel
Cantero, Oscar F.
Flynn, Robert W. V.
Garcia-Rodriguez, Luis
Harding, Abenah
Kollhorst, Bianca
Karlsson, Pär
Linnér, Love
MacDonald, Thomas M.
Odsbu, Ingvild
Plana, Estel
Ruigómez, Ana
Schink, Tania
Ziemiecki, Ryan
Andrews, Elizabeth B.
Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study
title Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study
title_full Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study
title_fullStr Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study
title_full_unstemmed Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study
title_short Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation: A Multinational Population-Based Cohort Study
title_sort cardiovascular safety of prucalopride in patients with chronic constipation: a multinational population-based cohort study
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739451/
https://www.ncbi.nlm.nih.gov/pubmed/31134512
http://dx.doi.org/10.1007/s40264-019-00835-0
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