Abstract

Most clinicians monitor blood pressure to estimate a patient's response to blood pressure-lowering therapy. However, the apparent change may not actually reflect the effect of the treatment, because a person's blood pressure varies considerably even without the administration of drug therapy. We estimated random background within-person variation, apparent between-person variation, and true between-person variation in blood pressure response to angiotensin-converting enzyme inhibitors after 3 months. We used meta-analytic mixed models to analyze individual patient data from 28 281 participants in 7 randomized, controlled trials from the Blood Pressure Lowering Trialists Collaboration. The apparent between-person variation in response was large, with SDs for change in systolic blood pressure/diastolic blood pressure of 15.2/8.5 mm Hg. Within-person variation was also large, with SDs for change in systolic blood pressure/diastolic blood pressure of 14.9/8.45 mm Hg. The true between-person variation in response was small, with SDs for change in systolic blood pressure/diastolic blood pressure of 2.6/1.0 mm Hg. The proportion of the apparent between-person variation in response that was attributed to true between-person variation was only 3% for systolic blood pressure and 1% for diastolic blood pressure. In conclusion, most of the apparent variation in response is not because of true variation but is a consequence of background within-person fluctuation in day-to-day blood pressure levels. Instead of monitoring an individual's blood pressure response, a better approach may be to simply assume the mean treatment effect.

Highlights

  • Using data from Ͼ28 000 patients in 7 trials of angiotensin-converting enzyme (ACE) inhibitors, which evaluated the effects of different agents within the same drug class and in different populations, we found that, after allowing for different mean blood pressure responses among the trials, there was only weak evidence of true between-person variation in blood pressure response

  • The magnitude of the variation was small: 95% of patients had a true change in systolic blood pressure that was within 5.1 mm Hg of the mean reduction for their trial with a corresponding figure of 1.9 mm Hg for diastolic blood pressure

  • This level of variability was much less than might be inferred from the apparent variation in response: 95% had an apparent change in systolic blood pressure that was within 29.7 mm Hg of the mean reduction for their trial with a corresponding figure of 15.2 mm Hg for diastolic blood pressure

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Summary

Study Design and Participants

The trials included in this study were those studies of ACE inhibitor– based regimens included in the Blood Pressure Lowering Treatment Trialists Collaboration,[7] an international program that collects data prospectively from trials of blood pressure–lowering treatments. The true between-person variation (SD) of treatment effects was calculated by taking the square root of each trial-specific model estimate of between person variance in treatment effects. These estimates do not include background withinperson variation. The true between-person variation (SD) of treatment effects was calculated by taking the square root of the meta-analytic model estimate of between-person variance in treatment effects (T). The apparent between-person variation (SD) of treatment effects was calculated by summing the meta-analytic model estimates of between-person variance in treatment effects (T) and within-person variance of change in blood pressure (W), and taking the square root (apparent variationϭ ͱT ϩ W). Analysis was done using MLwiN, with models fitted using iterative generalized least squares (Centre for Multilevel Modeling, University of Bristol)

Results
Background
A Changes in systolic blood pressure
Discussion
Disclosures
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