Should ambulatory blood pressure monitoring become an essential part of clinical hypertension trials?

Abstract

Although one measurement of blood pressure, taken at the office, already correlates reasonably well with cardiovascular morbidity and mortality, substitution of casual pressure by ‘usual blood pressure,’ defined as the average of multiple measurements on various occasions, improves the relationship considerably. While it may be true that obtaining a great many blood pressure readings at the office is more or less equivalent to 24-h ambulatory measurements for assessing usual pressure and cardiovascular risk [1], the latter technique is much more practical and yields results within 1 day. A major advantage of ambulatory blood pressure monitoring (ABPM) lies in its ability to provide an estimate of usual blood pressure without observer bias in patients engaged in normal activities [2]. Indeed, under a variety of conditions, ABPM has proven to be superior to conventional blood pressure measurements for the diagnosis of hypertension. Over the past 10 years, ABPM has gradually gained widespread acceptance and nowadays is also increasingly being used to assess therapeutic drug efficacy. The development of rather inexpensive, validated devices that can easily be worn by the patient make ABPM an interesting tool to employ in clinical trials. It is, therefore, surprising that the efficacy of antihypertensive drugs is often inferred from a few (office) readings only. In many trials, insufficient information or none at all is given regarding the time of measurement (e.g., morning or afternoon) or the circumstances under which the patient is being evaluated. Furthermore, many investigators seem to take it for granted that the magnitude of the reduction in blood pressure at one moment of the day is more or less equivalent to efficacy throughout the day. Certainly, this is a misconception. With 24-h blood pressure monitoring, it becomes possible to get an impression of the overall effectiveness of a particular drug. More specifically, ABPM allows for a better determination of some pharmacodynamic properties, such as onset and duration of action, modification of the diurnal blood pressure profile, and overall reduction in blood pressure [3]. For example, ABPM may detect that drugs thought to have a long duration of action do not work long enough to allow for once-daily dosing or vice versa. Furthermore, the pattern of the drop in blood pressure can be more accurately ascertained from ABPM readings, i.e., whether there is an excessive reduction in pressure in the first few hours after dosing or, the other way around, a very smooth drop. It should also be emphasized that even when the average 24-h blood pressure is reduced, this does not necessarily mean that this effect is sustained over the 24 h. Modern techniques to describe a drug's hypotensive potential, such as the trough-to-peak ratio or the smoothness index, definitely need ABPM for a proper assessment. Likewise, only ABPM offers the opportunity to ascertain whether a drug is effective during the early morning hours when pressure suddenly rises. Finally, apparent nonresponsiveness based on office readings can be confirmed or refuted only by ABPM.