Problems in the evaluation of antihypertensive therapy using the trough/peak ratio.

In 1988, the U.S. Food and Drug Administration proposed guidelines for the clinical evaluation of new antihypertensive drugs. According to these guidelines, the drug effect at trough (measured as the difference in blood pressure values from placebo) should be no less than one half to two thirds of the peak effect. Unfortunately, calculation of the trough/peak ratio suffers the consequences of many methodological, interpretative, practical, and epidemiological problems. When taking readings at short time intervals, noninvasive ambulatory blood pressure monitoring allows evaluation of blood pressure variability by means of several statistical parameters. Blood pressure variability, measured as the standard deviation of the overall 24-hour blood pressure measurements, has been demonstrated to be significantly correlated with target-organ damage in hypertensive patients. Blood pressure variability may not change with long-acting antihypertensive agents, but it may increase with short-acting ones. Therefore, assessment of the trough/peak ratio may be overcome by the evaluation of drug-induced changes in the standard deviation of the mean 24-hour blood pressure.