Chronotherapy of hypertension

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Abstract
Blood pressure displays appreciable predictable-in-time circadian variation. The chronotherapy of hypertension takes into account the clinically relevant features of the 24-h pattern of blood pressure, e.g. the accelerated morning rise and nighttime decline during sleep, plus potential administration circadian time determinants of the pharmacokinetics and dynamics of antihypertensive medications. Significant administration-time differences in the kinetics (i.e. chronokinetics) plus the beneficial and adverse effects (termed chronodynamics) of antihypertensive drugs are well known. Thus, bedtime, but not morning, dosing with cilnidipine significantly reduces nocturnal blood pressure. In addition, the dose-response curve, therapeutic coverage, and efficacy of the doxazosin gastrointestinal therapeutic system are all markedly dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime as opposed to upon awakening results in improved diurnal/nocturnal blood pressure ratio, such that the dosing time of valsartan can be chosen in relation to the dipper status of any given patient to improve therapeutic benefit and reduce cardiovascular risk. Nocturnal hypertension, which is characterized by the loss or even reversal of the expected 10-20% sleep-time blood-pressure decline, increases the risk of cardiac and cerebrovascular events. Chronotherapy provides a means of individualizing treatment of hypertension according to the circadian profile of blood pressure of each patient. The chronotherapeutic strategy constitutes a new option to optimize blood-pressure control and to reduce risk.