89260
document
Determining the trough-to-peak ratio in parallel-group trials . Systolic Hypertension in Europe ( SYST-EUR ) Trial Investigators . We explored how in parallel-group trials interindividual variability , correction for placebo effects , and smoothing of blood pressure profiles can be handled in measuring the trough-to-peak ratio in 244 individuals with isolated systolic hypertension ( > or = 60 years ) enrolled in the placebo-controlled Systolic Hypertension in europe Trial . Net treatment effects were computed by subtracting the mean changes from baseline during placebo ( n = 133 ) from those during active treatment ( n = 111 ) . At entry , systolic/diastolic pressures averaged 176/86 mm Hg in the clinic and 149/80 mm Hg on 24-hour ambulatory monitoring . With corrections applied for baseline and placebo , nitrendipine ( 10 to 40 mg/d ) , with the possible addition of enalapril ( 5 to 20 mg/d ) and/or hydrochlorothiazide ( 12.5 to 25 mg/d ) , reduced ( P < .001 ) these blood pressure values by 16.6/7.3 and 9.8/4.7 mm Hg , respectively . The net trough-to-peak ratios were first determined from blood pressure profiles ( 12 hours ) with 1-hour precision , synchronized by the morning and evening doses of the double-blind medication . According to the usual approach , disregarding interindividual variability , the systolic/diastolic net trough-to-peak ratios were 0.46/0.40 in the morning and 0.77/0.99 in the evening . In individual subjects , the baseline-adjusted trough-to-peak ratios were nonnormally distributed . We therefore used a nonparametric technique to calculate the net trough-to-peak ratios from the results in individual subjects . In the morning , these ratios averaged 0.25 systolic ( 95 % confidence interval , 0.09 to 0.41 ) and 0.15 diastolic ( 95 % confidence interval , 0.00 to 0.31 ) and in the evening , 0.19 and 0.36 ( 95 % confidence intervals , 0.00 to 0.38 and 0.14 to 0.56 ) , respectively . When the blood pressure profiles were smoothed by substituting the 1-hour averages by moving or fixed 2-hour averages or by Fourier modeling , the trough-to-peak ratios remained unchanged after the morning dose ( 0.20/0.13 , 0.20/0.14 , and 0.16/0.21 , respectively ) but tended to increase in the evening ( 0.32/0.38 , 0.28/0.40 , and 0.48/0.49 ) . In conclusion , the parallel-group analysis proposed makes it possible for one to correct the trough-to-peak ratio for baseline as well as placebo , to account for interindividual variability , and to calculate a confidence interval for the net trough-to-peak ratio . Accounting for interindividual variability reduces the trough-to-peak ratio . Smoothing affects the individualized net trough-to-peak ratios in an unpredictable way and should therefore be avoided .
89261
Intervention_Pharmacological
nitrendipine
89262
Intervention_Pharmacological
enalapril
89263
Intervention_Pharmacological
hydrochlorothiazide
89264
Outcome_Other
trough-to-peak ratio
89265
Outcome_Other
trough-to-peak ratio
89266
Outcome_Physical
systolic/diastolic pressures
89267
Outcome_Physical
blood pressure values
89268
Outcome_Other
net trough-to-peak ratios
89269
Outcome_Physical
blood pressure profiles
89270
Outcome_Physical
systolic/diastolic net trough-to-peak ratios
89271
Outcome_Other
baseline-adjusted trough-to-peak ratios
89272
Outcome_Other
net trough-to-peak ratios
89273
Outcome_Physical
blood pressure
89274
Outcome_Other
trough-to-peak ratios
89275
Outcome_Other
trough-to-peak ratio
89276
Outcome_Other
trough-to-peak ratio
89277
Outcome_Other
trough-to-peak ratio
89278
Outcome_Other
trough-to-peak ratios
89279
Participant_Sample-size
244
89280
Participant_Condition
isolated systolic hypertension
89281
Participant_Age
> or = 60 years )
89282
Participant_Condition
Systolic Hypertension