Confounding by Contraindication in a Nationwide Cohort Study of Risk for Death in Patients Taking Ibopamine

Confounding by Contraindication in a Nationwide Cohort Study of Risk for Death in Patients Taking Ibopamine

Hans Feenstra, MD, PhD;
Rick E. Grobbee, MD, PhD;
Bas A. in't Veld, MD, PhD; and
Bruno H.Ch. Stricker, MB, PhD

From Inspectorate for Health Care, Rijswijk; Erasmus University Medical School, Rotterdam; and Julius Center for Patient-Oriented Research, Utrecht University Medical School, Utrecht, the Netherlands.

Abstract

Background: 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.

Objective: 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.

Design: Retrospective cohort study.

Setting: The Netherlands.

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

Measurements: 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).

Results: 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.

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

Article and Author Information

Acknowledgment: The authors thank the general practitioners and pharmacists in the Netherlands who contributed information.
Grant Support: By the Inspectorate for Health Care of the Dutch Ministry for Health, Welfare, and Sports.
Requests for Single Reprints: Bruno H.Ch. Stricker, MB, PhD, Department of Epidemiology & Biostatistics, Erasmus University Medical School, Box 1738, 3000 DR Rotterdam, the Netherlands.
Current Author Addresses: Dr. Feenstra: Department of Internal Medicine, Albert Schweitzer Hospital, Box 444, 3300 AK Dordrecht, the Netherlands.
Dr. Grobbee: Julius Center for Patient Oriented Research, Box 85500, 3508 GA Utrecht, the Netherlands.
Dr. in't Veld: Department of Anesthesiology, Academic Medical Centre, Box 9600, 2300 RC Leiden, the Netherlands.
Dr. Stricker: Department of Epidemiology & Biostatistics, Erasmus University Medical School, Box 1738, 3000 DR Rotterdam, the Netherlands.
Author Contributions: Conception and design: H. Feenstra, R.E. Grobbee, B.A. in't Veld, B.H.Ch. Stricker.
Analysis and interpretation of the data: H. Feenstra, R.E. Grobbee, B.A. in't Veld, B.H.Ch. Stricker.
Drafting of the article: H. Feenstra, R.E. Grobbee, B.A. in't Veld, B.H.Ch. Stricker.
Critical revision of the article for important intellectual content: H. Feenstra, R.E. Grobbee, B.H.Ch. Stricker.
Final approval of the article: H. Feenstra, R.E. Grobbee, B.A. in't Veld, B.H.Ch. Stricker.
Statistical expertise: R.E. Grobbee, B.H.Ch. Stricker.
Obtaining of funding: B.H.Ch. Stricker.
Collection and assembly of data: H. Feenstra, B.A. in't Veld, B.H.Ch. Stricker.