Chronotherapy improves blood pressure control and reverts the non-dipper pattern in patients with resistant hypertension

Patients with resistant hypertension represent an important clinical problem due to their high cardiovascular risk and prevalence of target organ damage. Therapeutic strategies in resistant hypertension currently include adding another drug or changing drugs in search for a better synergic combination. Most patients, however, receive all their drugs in a single morning dose [J Hypertens. 2002;20:1097–1104]. We have evaluated the impact on the circadian pattern of BP of modifying the time of treatment without increasing the number of prescribed drugs. We studied 147 patients with resistant hypertension (79 men and 68 women), 60.1±12.0 years of age, who were receiving 3 antihypertensive drugs in a single morning dose. Patients were randomly assigned to one of two groups according to the modification in their treatment strategy: 1) Changing one of the drugs (interchange of an alpha-blocker and a CCB), but keeping all 3 in the morning. 2) The same approach but prescribing the new drug to be taken at bedtime. BP was sampled at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours at baseline and after 3 months of treatment with the new therapeutic scheme. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of BP on a per subject basis. There was a small and non-significant BP reduction when all drugs were still taken on awakening (0.5 and 0.7 mm Hg reduction in the 24h mean of systolic and diastolic BP; P>0.374). At baseline, only 22% of the patients in this group were dippers, and this percentage was further reduced to 15% after 3 months of therapy with all drugs on awakening. The BP reduction was statistically significant (8.6 and 5.9 mm Hg for systolic and diastolic BP; P<0.001) with one drug at bedtime. This effect was markedly larger in the nocturnal mean of BP. Thus, while only 13% of the patients in this group were dippers at baseline, 52% were already dippers after 3 months of therapy. Results from this prospective trial on patients with resistant hypertension indicate that time of treatment may be more important for BP control and for the proper modeling of the circadian BP pattern than just changing the drug combination