Confounding by contraindication in a nationwide cohort study of risk for death in patients taking ibopamine

Outcomes may differ in treated and untreated patients because of a contraindication for treatment in the latter that is independently associated with the outcome of interest.

To evaluate the effects of confounding by contraindication on risk factors for death in patients taking ibopamine after its use was restricted in early September 1995.

Retrospective cohort study.

The Netherlands.

1146 patients with congestive heart failure who were prescribed ibopamine at least once and for whom medication history and medical data were available.

Cardiovascular risk factors, clinical characteristics, and medication use. Each patient was assigned an index date (the date of death, or a random date for patients still alive at the end of the study).

In univariate analyses comparing patients with an index date before and those with an index date after 8 September 1995, the relative risk for death associated with current use of ibopamine was 3.02 (95% CI, 2.12 to 4.30) compared with 0.71 (CI, 0.53 to 0.96), respectively. In multivariate analyses, the risk for death was 2.62 (CI, 1.76 to 3.90) and 0.93 (CI, 0.84 to 1.02), respectively.

The marked inversion of the relative risk estimate can be considered a practical example of confounding by contraindication.