ROLE OF TROUGH TO PEAK EFFICACY IN THE EVALUATION OF ANTIHYPERTENSIVE THERAPY

BACKGROUND: The major outcome trials clearly demonstrate that there is benefit associated with treatment of hypertension, not only in a reduced incidence of stroke but also in a reduction in coronary heart disease. The latter reduction is, however, less than might be anticipated from epidemiological evidence. TWENTY-FOUR-HOUR BLOOD PRESSURE CONTROL: Although there is still no definitive evidence that 24-h blood pressure control will lead to improved outcomes compared with drugs that provide intermittent control, there is a large body of evidence showing that cardiovascular target organ damage is correlated with 24-h blood pressure measurements and supportive evidence showing that a fall in these measurements can predict a probable reduction in cardiovascular target organ damage. TROUGH:PEAK RATIO AS AN INDEX OF BLOOD PRESSURE CONTROL: The Food and Drug Administration guidelines on trough:peak ratio offer an index not only of the 'safety' of an antihypertensive agent but also of its duration of action over the recommended dosage interval. Ideally, an agent should have a trough:peak ratio that consistently exceeds 60% and does so throughout the recommended therapeutic dose range. When this aim is achieved, particularly with agents that have intrinsic long duration of action, the evidence suggests that blood pressure control is sustained well beyond the dosage interval, providing 'cover' for the poorly compliant patient. CONCLUSION: Epidemiological evidence indicates that optimal antihypertensive therapy should be based upon achieving smooth and consistent blood pressure control over a full 24 h. This is most likely to be achieved by long-acting antihypertensives that are characterized by having a high trough:peak ratio.