Evaluation of once-daily antihypertensive therapy

Abstract

The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension report has recommended long-acting, once-daily drugs as preferred therapy for the management of hypertension. The duration of action of an antihypertensive agent can be assessed in several ways. The decrease in clinical blood pressure at the end of the dosing interval has traditionally been the method for determining antihypertensive efficacy. However, this approach does not provide information about a drug's effects over the remainder of the 24-hour dosing interval. The trough-to-peak ratio has been proposed as an arithmetic index of a compound's maximum and minimum antihypertensive effects. This ratio can be obtained from multiple readings in an office setting or using data from 24-hour ambulatory blood-pressure monitoring. A simplified approach has been to compare a single office reading at the time of a drug's known maximum antihypertensive effect (peak) with the reduction in blood pressure at 24 hours (trough). Office readings have also been used to show that the same dose of a drug given once daily versus twice daily results in a similar trough blood pressure, confirming that once-daily therapy is appropriate. The 24-hour ambulatory blood pressure can be used to determine mean changes in daytime, evening, and night-time blood pressure to demonstrate the antihypertensive profile over the entire dosing interval. Finally, the finding of a persistent reduction in ambulatory blood pressure following substitution of placebo for an antihypertensive drug during chronic therapy (missed-dose technique) suggests that a compound decreases blood pressure for 48 hours or longer. Thus, it should be possible to demonstrate the effectiveness of once-daily antihypertensive therapy using one or more of the aforementioned methods.