Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo.
OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs.
Asmar
R
Hôpital Broussais, Paris, France.
Boutelant
S
Chaignon
M
Guedon
J
Topouchian
J
Mallion
JM
Safar
M