Changing the Timing of Antihypertensive Therapy to Reduce Nocturnal Blood Pressure in CKD: An 8-Week Uncontrolled Trial

Minutolo, Roberto; Gabbai, Francis B.; Borrelli, Silvio; Scigliano, R; Trucillo, Paolo; Baldanza, D; Laurino, Simona; Sara, Mascia,; Conte, Giuseppe; Nicola, Luca De

doi:10.1053/j.ajkd.2007.07.020

Cited by 112 publications

(72 citation statements)

References 35 publications

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“…18 This reduction was independent of changes in 24-hour BP with treatment, but significantly correlated with the decrease in asleep BP mean and increase in sleep-time relative BP decline, both therapeutic targets being better achieved with bedtime than morning ingestion of valsartan. 18 Another recent small study 3 reported similar findings, namely significant reduction of asleep BP mean and decreased urinary albumin excretion, after shifting one BP-lowering medication from morning to evening in 32 uncontrolled nondipper patients with CKD. In the trial reported here, albumin was greatly reduced in patients ingesting Ն1 hypertension medication at bedtime than in those ingesting all medications upon awakening.…”

Section: Discussionmentioning

confidence: 64%

“…2 Moreover, independent trials have documented that ingesting at least one BP-lowering medication at bedtime, compared with treatment with all medications upon awakening, is associated with increased BP control, significant lowering of sleep-time BP, decrease in the prevalence of nondipping, and reduction of urinary protein excretion. 3,4 The impact of bedtime chronotherapy on sleeptime BP regulation might be of clinical importance. This perspective is based on the growing number of studies, all based on ambulatory BP monitoring (ABPM), that have consistently shown that the sleep-time BP mean is a better predictor of cardio-vascular disease (CVD) events than the daytime or 24-hour BP means, 5-9 a relevant finding also documented for patients with chronic kidney disease (CKD).…”

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confidence: 99%

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Bedtime Dosing of Antihypertensive Medications Reduces Cardiovascular Risk in CKD

Hermida

Ayala

Mojón

et al. 2011

Journal of the American Society of Nephrology

238

181

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Time of ingestion of hypertension medications can affect circadian patterns of BP, but whether this translates into an effect on clinical outcomes is unknown. Here, in an open-label trial, we randomly assigned 661 patients with CKD either to take all prescribed hypertension medications upon awakening or to take at least one of them at bedtime. We measured 48-hour ambulatory BP at baseline and 3 months after any adjustment in treatment or, at the least, annually. After a median follow-up of 5.4 years, patients who took at least one BP-lowering medication at bedtime had an adjusted risk for total cardiovascular events (a composite of death, myocardial infarction, angina pectoris, revascularization, heart failure, arterial occlusion of lower extremities, occlusion of the retinal artery, and stroke) that was approximately one-third that of patients who took all medications upon awakening (adjusted HR 0.31; 95% CI 0.21 to 0.46; P Ͻ 0.001). Bedtime dosing demonstrated a similar significant reduction in risk for a composite outcome of cardiovascular death, myocardial infarction, and stroke (adjusted HR 0.28; 95% CI 0.13 to 0.61; P Ͻ 0.001). Furthermore, patients on bedtime treatment had a significantly lower mean sleep-time BP and a greater proportion demonstrated control of their ambulatory BP (56% versus 45%, P ϭ 0.003). Each 5-mmHg decrease in mean sleep-time systolic BP was associated with a 14% reduction in the risk for cardiovascular events during follow-up (P Ͻ 0.001). In conclusion, among patients with CKD and hypertension, taking at least one antihypertensive medication at bedtime improves control of BP and reduces the risk for cardiovascular events. A number of published prospective trials reviewed elsewhere 1 have reported clinically meaningful morning-evening, treatment-time differences in BP-lowering efficacy, duration of action, safety profile, and/or effects on the circadian BP pattern for different classes of hypertension medications. For instance, a once-daily evening, in comparison to morning, ingestion schedule of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors results in greater therapeutic effect on sleep-time BP and a significant increase in the sleep-time relative BP decline toward more of a dipping pattern, independent of the terminal half-life of each individual medication. 2 Moreover, independent trials have documented that ingesting at least one BP-lowering medication at bedtime, compared with treatment with all medications upon awakening, is associated with increased BP control, significant lowering of sleep-time BP, decrease in the prevalence of nondipping, and reduction of urinary protein excretion. 3,4 The impact of bedtime chronotherapy on sleeptime BP regulation might be of clinical importance. This perspective is based on the growing number of studies, all based on ambulatory BP monitoring (ABPM), that have consistently shown that the sleep-time BP mean is a better predictor of cardio-

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Section: Discussionmentioning

confidence: 64%

mentioning

confidence: 99%

Bedtime Dosing of Antihypertensive Medications Reduces Cardiovascular Risk in CKD

Hermida

Ayala

Mojón

et al. 2011

Journal of the American Society of Nephrology

238

181

View full text Add to dashboard Cite

show abstract

“…[30][31][32] Whether drug-induced effects on the circadian rhythm of blood pressure 44 are followed by similar effects on the arterial stiffness temporal pattern is not known. 45 Further study is needed to investigate the mechanisms involved in this phenomenon and to address its implications in our understanding of the circadian variation in cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

Diurnal variation of endothelial function and arterial stiffness in hypertension

et al. 2009

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“…The earliest uncontrolled trial of changing dose schedule to treat nondipping examined 32 nondipper subjects with CKD. 62 Average estimated GFR was 46 mL/min/1.73m 2 and subjects were hypertensive nondippers despite taking an average of 2.4 antihypertensive medications. During the trial one non diuretic antihypertensive medication was changed to be taken at bedtime and 24 hour ABPM was repeated at 8 weeks, and all but 4 of the 32 subjects became dippers.…”

Section: Interventions For Nondippingmentioning

confidence: 98%

The Complex Relationship Between CKD and Ambulatory Blood Pressure Patterns

Sinha

Agarwal

2015

Advances in Chronic Kidney Disease

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Hypertension and chronic kidney disease (CKD) frequently coexist, and both are risk factors for cardiovascular events and mortality. Among people with hypertension, the loss of the normal fall in nighttime BP, called nondipping, can only be diagnosed by ambulatory BP monitoring (ABPM), and is a risk factor for cardiovascular events. The pathophysiology of nondipping is complex, and CKD is an independent risk factor for non-dipping. In fact, non-dipping can be seen in as many as 80% of people with CKD. However, the evidence for nondipping as an independent risk factor or causal agent for adverse outcomes in CKD remains mixed. ABPM has been shown to be superior to clinic BP measurement for correlating with end organ damage and prognosis in CKD. This review covers the evidence for the use of ABPM in CKD, the evidence linking ABPM patterns to outcome in CKD, and the evidence for treatment of nondipping in CKD.

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Changing the Timing of Antihypertensive Therapy to Reduce Nocturnal Blood Pressure in CKD: An 8-Week Uncontrolled Trial

Cited by 112 publications

References 35 publications

Bedtime Dosing of Antihypertensive Medications Reduces Cardiovascular Risk in CKD

Bedtime Dosing of Antihypertensive Medications Reduces Cardiovascular Risk in CKD

Diurnal variation of endothelial function and arterial stiffness in hypertension

The Complex Relationship Between CKD and Ambulatory Blood Pressure Patterns

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