Cisapride and ventricular arrhythmia.
OBJECTIVE
We aimed to examine the association between cisapride and ventricular arrhythmia, and examine the relationship to dose and CYP3A4 inhibitors.


METHODS
A nested case-control study was conducted in Medicaid beneficiaries exposed to cisapride, metoclopramide or a proton pump inhibitor (PPI) from 1999 to 2000. Cases were hospitalized with a principal International Classification of Diseases-9 code indicating sudden cardiac death or ventricular arrhythmia. Controls had at least as much event-free person time following the study prescription as its matched case.


RESULTS
A total of 145 cases and 7250 controls were identified. The unadjusted rate ratio for cisapride vs. PPIs was 1.49 (95% confidence interval 0.96, 2.25). The adjusted odds ratio (OR) for cisapride vs. PPIs was 2.10 (1.34, 3.28). Excluding persons in managed care, the adjusted OR for cisapride was 2.92 (1.55, 5.49). In the initial prescription period, the adjusted OR for cisapride vs. PPIs was 7.85 (1.95, 31.60). Non-arrhythmogenic CYP3A4 inhibitors were not associated with an increased risk in users of cisapride or PPI inhibitors. The OR for potentially arrhythmogenic CYP3A4 inhibitors was 3.79 (1.76, 8.15) in cisapride users and 3.47 (2.06, 5.83) in PPI users.


CONCLUSIONS
Cisapride was associated with a doubling to tripling of the risk of hospitalization for ventricular arrhythmia, and a nearly eightfold risk in the initial prescription period. Although use of potentially arrhythmogenic CYP3A4 inhibitors was associated with an increased risk, this appears to be due to a direct effect of the drugs themselves rather than an interaction with cisapride.
Hennessy
Sean
S
Department of Biostatistics and Epidemiology, and Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. hennessy@mail.med.upenn.edu
Leonard
Charles E
CE
Newcomb
Craig
C
Kimmel
Stephen E
SE
Bilker
Warren B
WB
D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D020117:Cisapride / Q000008:administration & dosage / Q000009:adverse effects*; D051544:Cytochrome P-450 CYP3A; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage; D008875:Middle Aged; D018579:Patient Selection; D017891:Pharmacoepidemiology; D017494:Proton Pumps / Q000008:administration & dosage; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D005765:Gastrointestinal Agents; D017494:Proton Pumps; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008787:Metoclopramide; D020117:Cisapride