The nested case-control design is an efficient method of sampling from a cohort that is increasingly used in cardiovascular research to study causal relationships. This methodology can be used to analyze data from large administrative databases to evaluate potential cardiovascular adverse effects of medications. Using a nested case-control approach, this study investigated whether amiodarone therapy for atrial fibrillation (AF) was associated with an increased risk of bradyarrhythmia requiring permanent pacemaker insertion. This previously unpublished adverse effect of amiodarone was evaluated in a province-wide database of Quebec residents with AF and a previous myocardial infarction. We found that amiodarone use was associated with a greater than twofold increase in the risk of permanent pacemaker insertion after adjusting for potential confounding factors and exposures to other cardiovascular medications. The effect of amiodarone dose on this risk was then evaluated with survival analysis using Cox regression with time-dependent covariates. The risk of permanent pacemaker insertion was found to be dose-dependent and greatest during the initial months of treatment when higher doses of amiodarone were used. The effect of amiodarone dose was reanalyzed using nested case-control methods in order to compare nested case-control and survival analysis approaches for evaluating time-dependent exposure. Expectedly similar risk estimates were obtained with superior computational efficiency using nested case-control methods. In conclusion, amiodarone is associated with a dose-dependent increased risk of permanent pacemaker insertion that should be taken into consideration when initiating amiodarone therapy for elderly patients with AF. The nested case-control design is a useful alternative for analysis of a cohort with time-dependent exposure, particularly when studying rare outcomes in large databases.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.84242 |
| Date | January 2003 |
| Creators | Essebag, Vidal |
| Contributors | Pilote, Louise (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Epidemiology and Biostatistics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002031418, proquestno: AAINQ98248, Theses scanned by UMI/ProQuest. |
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