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Systematic review with meta‐analysis: highly selective 5‐HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation
Author(s) -
Shin A.,
Camilleri M.,
Kolar G.,
Erwin P.,
West C. P.,
Murad M. H.
Publication year - 2014
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12571
Subject(s) - medicine , meta analysis , constipation , chronic constipation , lubiprostone , gastroenterology , 5 ht4 receptor , intensive care medicine , agonist , receptor
Summary Background Highly selective 5‐ HT 4 agonists have been suggested for the treatment of chronic constipation ( CC ). Aim To assess the effects of highly selective 5‐ HT 4 agonists (prucalopride, velusetrag or naronapride) on patient‐important clinical efficacy outcomes and safety in adults with CC . Methods We searched the medical literature in January 2013 using MEDLINE /Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5‐ HT 4 agonists in adults with CC , with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention‐to‐treat analyses, pooled using a random‐effects model, and reported as relative risk ( RR ), mean differences, or standardised mean differences with 95% confidence intervals ( CI ). Results Main outcomes included stool frequency, Patient‐Assessment of Constipation Quality of Life ( PAC ‐ QOL ), PAC of symptoms ( PAC ‐ SYM ) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5‐ HT 4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements ( SCBM )/week ( RR = 1.85; 95% CI 1.23–2.79); mean ≥1 SCBM over baseline ( RR = 1.57; 95% CI 1.19, 2.06); ≥1 point improvement in PAC ‐ QOL and PAC ‐ SYM scores. The only active comparator trial of prucalopride and PEG 3350 suggested PEG 3350 is more efficacious for some end points. Adverse events were more common with highly selective 5‐ HT 4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride. Conclusion Demonstration of efficacy on patient‐important outcomes and a favourable safety profile support the continued use and development of highly selective 5– HT 4 agonists in the treatment of chronic constipation.