AMBULATORY MONITORING UNCORRECTED FOR PLACEBO OVERESTIMATES LONG-TERMANTIHYPERTENSIVE ACTION

This study compares blood pressure (BP) changes during active antihype rtensive treatment and placebo as assessed by conventional and ambulat ory BP measurement. Older patients (greater than or equal to 60 years, n=337) with isolated systolic hypertension by conventional sphygmoman ometry at the clinic were randomized to placebo or active treatment co nsisting of nitrendipine (10 to 40 mg/d), with the possible addition o f enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d ). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8 /1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP) ; these decreases represented 43%/23%, 20%/24%, and 30%/23% of the cor responding BP fall during active treatment. After subtraction of place bo effects, the net BP reductions during active treatment averaged onl y 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytim e BPs. respectively. The effect of active treatment was also subject t o diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) a nd 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with convent ional than with ambulatory measurement. Regardless of whether BP is me asured by conventional sphygmomanometry or ambulatory monitoring, a su bstantial proportion of the long-term BP changes observed during activ e treatment may be attributed to placebo effects. Thus, ambulatory mon itoring uncorrected for placebo or control observations, like conventi onal sphygmomanometry overestimates BP responses in clinical trials of long duration.