Administration-Time-Dependent Effects of Hypertension Treatment on Ambulatory Blood Pressure in Patients With Chronic Kidney Disease

Abstract

Many published prospective trials have reported clinically meaningful morning-evening, treatment-time differences in the blood pressure (BP)-lowering efficacy, duration of action, and safety of most classes of hypertension medications. Most important, it was recently documented that routine ingestion of the full daily dose of ≥1 hypertension medications at bedtime, compared with ingestion of all of them upon awakening, significantly reduces cardiovascular disease (CVD) events. Nocturnal hypertension and non-dipping (<10% decline in the asleep relative to the awake BP mean), as determined by ambulatory BP monitoring (ABPM), are frequent in chronic kidney disease (CKD) and both are associated with increased CVD risk. Here, we investigated the influence of hypertension treatment time on the circadian BP pattern and degree of BP control of hypertensive patients with CKD evaluated by 48-h ABPM. This cross-sectional study evaluated 2659 such patients (1585 men/1074 women), 64.9 ± 13.2 (mean ± SD) yrs of age, enrolled in the Hygia Project, involving primary care centers of northwest Spain and designed to evaluate prospectively CVD risk by ABPM; 1446 were ingesting all BP-lowering medications upon awakening, whereas 1213 patients were ingesting ≥1 medications at bedtime. Among the latter, 359 patients were ingesting all medications at bedtime, whereas 854 were ingesting the full daily dose of some medications upon awakening and the others at bedtime. Those ingesting all medications upon awakening had significantly higher total cholesterol and low-density lipoprotein (LDL) cholesterol than those ingesting ≥1 medications at bedtime. Moreover, patients ingesting all medications at bedtime had the lowest fasting glucose, serum creatinine, and uric acid. Ingestion of ≥1 medications at bedtime was significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than treatment with all medications upon awakening. The sleep-time relative SBP decline was significantly attenuated in patients ingesting all medications upon awakening (p < .001). Thus, the prevalence of non-dipping was significantly higher when all hypertension medications were ingested upon awakening (68.3%) than when ≥1 of them was ingested at bedtime (54.2%; p < .001 between groups), and even further attenuated (47.9%) when all of them were ingested at bedtime (p < .001). Additionally, the prevalence of a riser BP pattern, associated with highest CVD risk, was much greater (21.5%) among patients ingesting all medications upon awakening, compared with those ingesting some (15.7%) or all medications at bedtime (10.6%; p < .001 between groups), independent of CKD severity (disease stage). The latter group also showed a significantly higher prevalence of properly controlled ambulatory BP (p < .001) that was achieved by a significantly lower number of hypertension medications (p < .001) compared with patients treated upon awakening. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of a blunted nightti...

The Complex Relationship Between CKD and Ambulatory Blood Pressure Patterns

“…A recent cross sectional study of 48 hour ABPM in 2,659 patients with CKD from the Hygia Project cohort looked at this question and found that the 1,213 patients taking at least one BP medication at bedtime had a significantly lower prevalence of nondipping at 54% versus the 68% prevalence in the 1,446 patients who took all their antihypertensive medications in the morning. 61 While cross sectional and prospective observational studies may suggest associations, a causal link can only be established by interventional randomized controlled trials. The earliest uncontrolled trial of changing dose schedule to treat nondipping examined 32 nondipper subjects with CKD.…”

Evening -Versus Morning- Dosing Drug Therapy for Chronic Kidney Disease Patients with Hypertension: A Systematic Review

“…Six trials [19,20,21,22,23,24] examining the antihypertensive chronotherapy of CKD patients were excluded; the reasons for exclusion are reported in Table 3.…”

“…Among the excluded trials, the results of a three-way randomized crossover trial [22] showed that, taking drugs in the evening did not significantly reduce nocturnal hypertension compared to morning dosing of antihypertensive medications. The results of cross-sectional study [19] evaluated 2659 patients revealed that the prevalence of non-dipping was significantly higher when all hypertension medications were ingested upon awakening (68.3%) than when ≥1 of them was ingested at bedtime (54.2%; P < 0.001 between groups), and even further attenuated (47.9%) when all of them were ingested at bedtime ( P < 0.001). In an uncontrolled 8-week study [21], Minutolo et al demonstrated that with administration of antihypertensive medications at night, the night/day ratio of mean ambulatory blood pressure decreased in 93.7% of patients, with normal circadian rhythm restored in 87.5%.…”

Resistant Arterial Hypertension: Is the Consensus Between Conservative and Interventional Therapy Possible?

“…[25], в котором пока-зано убедительное преимущество схемы антигипер-тензивной терапии с назначением ≥1 препарата на ночь по сравнению с приемом всех препаратов утром по сни-жению уровня АД в ночные часы у 2659 пациентов бе-лой расы с АГ и ХБП. Можно предположить, что аф-роамериканцы оказываются менее чувствительными к смене времени приема антигипертензивных средств.…”