Trough: peak ratios for antihypertensive agents: methodological considerations

The trough: peak ratio for the response to an antihypertensive drug is a clinically meaningful parameter only when the index has been derived and calculated from an appropriately designed and conducted study. The original draft guidelines made no recommendations concerning the most appropriate methodology, hence trough: peak values have been calculated from studies in research units, in the clinic and using ambulatory blood pressure monitoring. Furthermore, some studies quoted single values based upon mean data, whereas others presented trough: peak ratios in individual subjects. To date only the use of the 'research unit' approach and ambulatory monitoring have been subject to any form of validation. Both approaches have advantages and disadvantages but in each instance common factors emerge. These indicate that any study defining trough: peak ratios should incorporate a placebo assessment, steady state treatment, randomized cross-over design (ideally), estimates in individual patients, two or more dose levels (ideally), and, in the case of ambulatory blood pressure monitoring, the study of patients who achieve a given blood pressure reduction at the time of peak response.