Effects of Time of Day of Treatment on Ambulatory Blood Pressure Pattern of Patients With Resistant Hypertension

Abstract

Abstract-Patients with resistant hypertension present high prevalence of a non-dipper blood pressure pattern. Recent results indicate that non-dipping is related partly to the absence of 24-hour therapeutic coverage in patients treated with single morning doses. Accordingly, we investigated the impact of treatment time on the blood pressure pattern in 700 patients with resistant hypertension on the basis of clinic measurements who were studied by 48-hour ambulatory monitoring. Among them, 299 patients received all their medication on awakening, and 401 were taking Ն1 antihypertensive drug at bedtime. The percentage of patients with controlled ambulatory blood pressure was double in patients taking 1 drug at bedtime (Pϭ0.008). Among the 578 patients with true resistant hypertension, subjects receiving 1 drug at bedtime showed a significant reduction in the 24-hour mean of systolic and diastolic blood pressure (3.1 and 1.6 mm Hg, respectively; PϽ0.011). This reduction was much more prominent during nighttime (5.1 and 3.0 mm Hg; PϽ0.001). Accordingly, the diurnal/nocturnal blood pressure ratio was significantly increased by 2.7 and the prevalence on non-dipping reduced (56.9 versus 81.9%; PϽ0.001) in patients taking 1 drug at bedtime. Compared with patients receiving all drugs on awakening, subjects with 1 drug at bedtime also showed significant reductions in the average values of glucose, cholesterol, fibrinogen, and urinary albumin excretion (PϽ0.011). In patients with resistant hypertension, pharmacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient to improve control and to avoid the non-dipper pattern associated to higher cardiovascular risk. Key Words: blood pressure monitoring, ambulatory Ⅲ circadian rhythm H ypertension has been defined as resistant to treatment, or refractory, when a therapeutic plan that has included attention to lifestyle measures and the prescription of Ն3 antihypertensive drugs in adequate doses has failed to lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) sufficiently. 1,2 Patients with resistant hypertension are at a greater risk for stroke, renal insufficiency, and morbid cardiovascular events than patients whose blood pressure (BP) is well controlled by medical therapy. 3 Indeed, in patients with resistant hypertension, poor BP control may engender a consistent amount of target organ damage, and this, in turn, may become a cause of resistance to treatment. 4 It has also been reported that most patients receiving antihypertensive therapy show a "white-coat effect" that could cause an overestimation of their real BP. 4,5 The impact of this effect on the occurrence of resistant hypertension seems to be highly variable among different studies, ranging from 20% up to 43% of the patients. 6,7 Ambulatory BP monitoring (ABPM) is the only method to differentiate "isolated office resistant hypertension" from "true resistant hypertension." [5][6][7] It has thus been suggested that ABPM should be performed as an...

Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing—a multicenter, open-label randomized study

“…Hermida et al reported that antihypertensive drugs given in the morning increased the prevalence of non-dipping blood pressure from 38 to 62% in resistant hypertensive patients. 26 Thus, the best method of tailoring the treatment of nondippers is a major concern of chronotherapy. Uzu and Kimura 27 reported that hydrochlorothiazide restores the diminished nocturnal blood pressure decline, and shifts circadian rhythm of blood pressure from a non-dipper to a dipper profile.…”

Update in New Medications for Primary Care

“…In a recent trial of patients with resistant hypertension (n = 250), investigators randomly assigned patients to receive one of their drugs at bedtime versus usual care. 41 Bedtime treatment resulted in a 9-mmHg drop in mean systolic blood pressure. Implications for practice are to: (1) consider using fixed combination drugs to improve adherence and potentially decrease cost, (2) include a diuretic in multi-drug regimens and diurese patients aggressively, (3) add spironolactone if needed, and (4) consider giving one drug at bedtime to improve morning blood pressure control.…”

Assessment and management of resistant hypertension

“…Bedtime dosing can lower nocturnal blood pressure by 5.2 mm Hg (p < 0.001) and potentially reduce mortality and cardiovascular events by 61% (p < 0.001). 9,42,43 However, further trials are needed to confirm these findings in patients with hypertension and in those with resistant hypertension. 11…”