Chronotherapy in hypertensive patients: administration–time dependent effects of treatment on blood pressure regulation

Abstract

Ambulatory blood pressure measurements (ABPM) correlate more closely with target organ damage and cardiovascular events than clinical cuff measurements. ABPM reveals the significant circadian variation in BP, which in most individuals presents a morning increase, small post-prandial decline, and more extensive lowering during nocturnal rest. However, under certain pathophysiological conditions, the nocturnal BP decline may be reduced (nondipper pattern) or even reversed (riser pattern). This is clinically relevant since the nondipper and riser circadian BP patterns constitute a risk factor for left ventricular hypertrophy, microalbuminuria, cerebrovascular disease, congestive heart failure, vascular dementia and myocardial infarction. Hence, there is growing interest in how to best tailor and individualize the treatment of hypertension according to the circadian BP pattern of each patient. Significant administration-time differences in the kinetics and in the beneficial and adverse effects of antihypertensive medications are well known. Thus, bedtime dosing with nifedipine gastrointestinal therapeutic system (GITS) is more effective than morning dosing, while also significantly reducing adverse effects. The therapeutic coverage and efficacy of doxazosin GITS are dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime, as opposed to upon wakening, results in an improved diurnal/nocturnal BP ratio, increased percentage of controlled patients, and significant reduction in urinary albumin excretion in hypertensive patients. Chronotherapy provides a means of individualizing the treatment of hypertension according to the circadian BP profile of each patient, and constitutes a new option to optimize BP control and reduce the risk of cardiovascular disease.

Keywords::

• ambulatory monitoring
• antihypertensive therapy
• blood pressure
• chronopharmacodynamics
• chronotherapy
• circadian variation
• dipper
• hypertension
• nondipper

Acknowledgements

Some of the trials summarized here were supported, in part, by grants from Dirección General de Investigación, Ministerio de Educación y Ciencia (SAF2006–6254); Xunta de Galicia (PGIDIT03-PXIB-32201PR); Hospital Clínico Universitario de Santiago; and Vicerrectorado de Investigación, University of Vigo.