Methodology to determine duration of action for antihypertensive drugs

To review and comment on methods used to assess the duration of action of antihypertensive drugs.

A MEDLINE search (1966-June 2000) using key terms such as trough-to-peak ratio and ambulatory blood pressure monitoring was conducted.

An article was considered for this review if it pertained to the assessment of the duration of action of antihypertensive drugs. Special attention was given to articles dealing with methodologic aspects.

Antihypertensive drugs with a long duration of action are thought to provide better therapeutic coverage against hypertensive complications compared with that of short-acting agents. Measuring blood pressure at the end of the dosing interval may be a way to assess the duration of action of a drug. However, the use of high doses of a short-acting agent to obtain sufficient effect when at trough concentrations can potentially cause dose-related adverse effects at the peak time, contributing to nonadherence to therapy and thus to adverse outcomes. To alleviate this problem, the US Food and Drug Administration (FDA) has conceptualized the trough-to-peak (T:P) ratio. Although this arithmetic index has since been widely used to characterize the duration and safety of blood pressure control achieved by antihypertensive agents, several methodologic flaws limit its interpretation in the clinic. Ambulatory blood pressure monitoring (ABPM) is a more reliable approach to assess the duration of action and outcome of antihypertensive therapy.

Different methodologic approaches exist to evaluate the duration of action of antihypertensive drugs. Although the T:P ratio has been suggested by the FDA, it is difficult to establish a fair comparison among various antihypertensive agents based solely on this index. Treatment evaluation based on ABPM may be preferable to those guided by T:P because ABPM is more reproducible and is now established as a predictor of cardiovascular risk.