Reproducibility of home, ambulatory, and clinic blood pressure: implications for the design of trials for the assessment of antihypertensive drug efficacy

The objective of this work is to compare the reproducibility of blood pressure measured in the clinic (CBP), at home (HBP) and with ambulatory monitoring (ABP), and to assess its implications on the accuracy of trials for the assessment of antihypertensive drug efficacy. Study 1: The reproducibility of CBP (one visit), HBP (2 days), and ABP (24 hours) was quantified using the standard deviation of differences (SDD) between repeated measurements in 137 untreated subjects with elevated CBP. The number of subjects required in a comparative clinical trial aiming to detect a difference in the antihypertensive effect of two drugs of 10/5 mmHg (systolic/diastolic blood pressure) was calculated for each blood pressure measurement technique. Study 2: A crossover trial comparing lisinopril versus losartan was conducted using CBP, HBP and ABP in 27 hypertensive subjects. Study 1: HBP provided the lowest SDD values (6.9/4.7 mmHg for systolic/diastolic blood pressure, compared to 8.3/5.6 for ABP and 11.0/6.6 for CBP). Using HBP the number of subjects needed for a comparative trial was reduced by 30% compared to using ABP and by 60% compared to CBP. Study 2: Lisinopril was more effective than losartan in reducing CBP, ABP, and HBP. Using HBP a false positive result (type I error) was 20 times less probable (p=0.0003) compared to using ABP (p=0.005) and 40 times less probable compared to CBP (p=0.01). Only HBP ensured a clinically important difference in the antihypertensive drug effect of at least 3-4 mmHg. HBP seems to have superior reproducibility compared to both CBP and ABP. HBP monitoring can improve the accuracy of antihypertensive drug trials reducing thereby the sample size required.