Brief Communication
American Journal of Hypertension (2008) 21 14–16 doi:10.1038/ajh.2007.21
Carryover Effects After Cessation of Drug Treatment: Trophies or Dreams?
Thomas Lumley1,2, Kenneth M Rice1,2 and Bruce M Psaty3,4,5
- 1Cardiovascular Health Research Unit, Seattle, Washington, USA
- 2Department of Biostatistics, University of Washington, Seattle, Washington, USA
- 3Department of Medicine, University of Washington, Seattle, Washington, USA
- 4Department of Epidemiology, University of Washington, Seattle, Washington, USA
- 5Department of Health Services, University of Washington, Seattle, Washington, USA.
Correspondence: Thomas Lumley, (tlumley@u.washington.edu)
Received 22 May 2007; First Decision 14 June 2007; Accepted 30 June 2007.
Abstract
Background
In randomized trials of primary prevention, there has been interest in the persistence of a beneficial effect of therapy after treatment has been stopped. We investigated the impact of measurement error in the outcome on results of the trial of preventing hypertension (TROPHY), a trial of candesartan vs. placebo for preventing hypertension in prehypertensive subjects.
Methods
We simulated the TROPHY study design, assuming that candesartan reduced blood pressure by 8/6 mm Hg during treament, but had no carryover effect after treatment stopped. We simulated individual true blood pressures in the TROPHY-eligible range of 130–140 mm Hg for systolic blood pressure and 80–90 mm Hg for diastolic blood pressure, and added individual measurement variablility. As in TROPHY, incident hypertension was defined as any three occurrences of systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg.
Results
In the absence of any carryover effect, typical incidence curves for time to hypertension were similar to those from TROPHY. A significant difference in cumulative incidence 2 years after stopping treatment was detected in 80% simulated studies, giving a Type I error rate of 80%.
Conclusions
The published data from TROPHY are consistent with a lack of carryover effect of candesartan.
American Journal of Hypertension (2008) 21 14–16 doi:10.1038/ajh.2007.21
