Carryover effects after cessation of drug treatment: trophies or dreams?
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 treatment, 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 variability. 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.
Lumley
Thomas
T
Cardiovascular Health Research Unit, Seattle, Washington, USA. tlumley@u.washington.edu
Rice
Kenneth M
KM
Psaty
Bruce M
BM
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D003198:Computer Simulation; D003951:Diagnostic Errors / Q000517:prevention & control; D004334:Drug Administration Schedule; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D015994:Incidence; D008955:Models, Cardiovascular; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012107:Research Design; D013599:Systole; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan