Canadian valsartan study in patients with mild-to-moderate hypertension

Lasko, B.; Laplante, A.; Hebert, Daniel N.; Bonnefis-Boyer, Sophie

doi:10.1097/00126097-200104000-00005

Cited by 14 publications

(8 citation statements)

References 24 publications

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“…However, it might be an inappropriate choice to treat nondipper hypertensives. Corroborating early findings, 3,4 results from this study indicate that a single daily dose of 160 mg/d of valsartan in the morning highly reduces BP smoothly over the 24 hours on the basis of high SI and T:P. The same dose of valsartan taken before bedtime resulted in comparable BP reduction during the 24 hours while highly improving the diurnal-nocturnal ratio of BP and thus, significantly reducing the incidence of nondippers. Whether this time-dependent effect is a class-related feature applicable to all ARBs or is specific to valsartan awaits future investigation.…”

Section: Discussionsupporting

confidence: 81%

“…Morning once-a-day dosing ranging from 80 to 320 mg/d results in BP reduction throughout the entire 24 hours. 3,4 The trough-to-peak ratio (T:P; the average BP reduction during the last 2 hours of the dosing interval compared with the average of the maximal reduction in BP over 2 consecutive hours 5 ) has been demonstrated to be Ͼ75%, 4 confirming that a single morning dose of valsartan provides effective BP control throughout the day without alteration of the circadian pattern of BP variation. 3 This circadian variation in BP represents, on the one hand, the influence of internal factors such as ethnicity, gender, autonomic nervous system tone, vasoactive hormones, and hematologic and renal variables.…”

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confidence: 97%

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Administration Time–Dependent Effects of Valsartan on Ambulatory Blood Pressure in Hypertensive Subjects

et al. 2003

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Abstract-This study investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects (30 men and 60 women), 49.0Ϯ14.3 (meanϮSD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan (PϽ0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; PϾ0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% (PϽ0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation. Valsartan is an orally active, specific and selective ARB. 2 After a single oral morning dose, the onset of its BP-lowering action is within 2 hours, with peak effect occurring within 4 to 6 hours. Morning once-a-day dosing ranging from 80 to 320 mg/d results in BP reduction throughout the entire 24 hours. 3,4 The trough-to-peak ratio (T:P; the average BP reduction during the last 2 hours of the dosing interval compared with the average of the maximal reduction in BP over 2 consecutive hours 5 ) has been demonstrated to be Ͼ75%, 4 confirming that a single morning dose of valsartan provides effective BP control throughout the day without alteration of the circadian pattern of BP variation. 3 This circadian variation in BP represents, on the one hand, the influence of internal factors such as ethnicity, gender, autonomic nervous system tone, vasoactive hormones, and hematologic and renal variables. 6 BP is also affected by a variety of external factors, including ambient temperature/ humidity, physical activity, emotional state, alcohol or caffeine consumption, meal composition, and sleep/wake routine. 7,8 Because the main steps in the mechanisms regulating BP are circadian-stage dependent, 7 it is not surprising that antihypertensive medications might display a circadian time dependency in their pharmacokinetics and effects. 6 Despite the great number of publishe...

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Section: Discussionsupporting

confidence: 81%

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confidence: 97%

Administration Time–Dependent Effects of Valsartan on Ambulatory Blood Pressure in Hypertensive Subjects

et al. 2003

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“…Plasma Ang II level measurements in human volunteers have confirmed that some AT 1 -receptor blockade persists at least 24 hours after valsartan administration, in accordance with the sustained 24 hours BP control with once-daily dosing of valsartan [15]. It appears that the relationship between the degree of RAS inhibition and BP is not linear.…”

Section: Pharmacodynamicsmentioning

confidence: 71%

Valsartan in The Treatment of Hypertension

et al. 2005

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Valsartan is a widely used, efficacious and very well-tolerated antihypertensive agent. By specifically blocking the action of angiotensin II on the angiotensin Type 1 receptor, valsartan reduces unwanted effects of angiotensin II, such as aldosterone, vasopressin and endothelin secretion, vasoconstriction, diuresis, endothelial cell hyperplasia, mitogenesis, induction of growth factors and production of collagen. Valsartan has a simple pharmacokinetic profile and requires no metabolism to become active. The dose-related efficacy of valsartan has been clearly demonstrated and the tolerability profile is similar to placebo. Clinical trials in elderly patients show good efficacy and high responder rates with the same doses as in younger patients. Valsartan is available as 80-, 160-and 320-mg tablets, and also in the same doses in combination with hydrochlorothiazide, 12.5 or 25 mg. Availability varies between countries. Beyond the reduction of blood pressure, valsartan is indicated for use in several countries in patients with heart failure and in patients post myocardial infarction, based on the results of the large-scale Valsartan Heart Failure Trial and VALsartan In Acute myocardial iNfarcTion trials. Valsartan has also been shown, in the Valsartan Antihypertensive Long-term Evaluation trial, to reduce the risk of developing new-onset diabetes in hypertensive patients at high risk of cardiac events.

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“…This success was achieved in patients less than optimally responsive to monotherapy with a widely prescribed ARB, valsartan, at its recommended starting dose of 80 mg/day. Various studies of valsartan have been predicated on the expectation that the full response to the starting dose will be realised within 4 weeks and that further blood pressure reductions cannot be expected after that time with the 80 mg/day dose [19][20][21][22] . It has been suggested that switching to combination therapy with agents that lower blood pressure through complementary mechanisms is more likely to achieve a satisfactory reduction in blood pressure than increasing the dose of ARB monotherapy 23 .…”

Section: Discussionmentioning

confidence: 99%