Combined Blockade of the Renin-Angiotensin System With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Antagonists

Azizi, Michel; Ménard, Joël

doi:10.1161/01.cir.0000131449.94713.ad

Cited by 185 publications

(129 citation statements)

References 86 publications

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“…The study design allowed for comparison of effects of treatments on PRA and PRC at 24 h after dose (day 42 measurement) and 72 h after dose (day 63 measurement, following placebo doses on days 61 and 62). Reduction in PRA is a direct measure of renin system inhibition, and an indirect measure of the effect of ACE inhibitors and ARBs to prevent the formation or action of angiotensin (Ang) II, respectively (as this stimulates a reactive rise in PRA through the short feedback loop 15 ). Our results show that renin system inhibition provided by active treatment with aliskiren 300 mg (day 42, 58% reduction in PRA) was fully maintained 72 h after dosing (day 63, 63% reduction in PRA).…”

Section: Discussionmentioning

confidence: 99%

Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study

et al. 2009

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Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h dosing interval are desirable. The primary objective of this study was to compare the 24-h mean ambulatory BP reductions from baseline after a simulated missed dose of the direct renin inhibitor aliskiren, irbesartan or ramipril. In this double-blind study, 654 hypertensive patients (24-h mean ambulatory diastolic BP (MADBP) X85 mm Hg) were randomized 1:1:1 to once-daily aliskiren 150 mg, irbesartan 150 mg or ramipril 5 mg. Doses were doubled after 2 weeks. At day 42, patients were again randomized equally within each group to receive 1 day of placebo ('missed dose') on either day 42 or day 49. Patients with a successful 24-h ambulatory BP measurement at baseline and on day 42/49 were included in the analyses. The 24-h mean ambulatory systolic BP (MASBP)/MADBP reductions from baseline after a missed dose of aliskiren 300 mg (9.3/7.0 mm Hg) were similar to irbesartan 300 mg (9.5/7.3 mm Hg) and significantly larger than ramipril 10 mg (7.1/5.0 mm Hg, Pp0.008). Loss of BP-lowering effect with aliskiren in the 24 h after a missed dose (1.0/0.7 mm Hg for 24-48-h vs 0-24-h MASBP/MADBP) was significantly lower than with irbesartan (3.6/2.2 mm Hg, Po0.01) or ramipril (4.0/2.6, Po0.0001). This equates to maintenance of 91/91% of the MASBP/MADBP-lowering effect with aliskiren, greater than irbesartan (73/77%) or ramipril (64/65%). The incidence of adverse events was similar across treatments (32.9-36.0%), although ramipril treatment was associated with an increased incidence of cough (ramipril, 6.1%; aliskiren, 0.5%; irbesartan, 1.8%). Aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24-48 h period after dose than irbesartan 300 mg or ramipril 10 mg.

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Section: Discussionmentioning

confidence: 99%

Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study

et al. 2009

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“…4 However, optimized RAAS suppression is difficult to achieve with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate compen-satory feedback mechanisms that result in renin release and increased PRA. 5,6 ACE inhibitors cause an increase in PRA and Ang I, which is then available for conversion to Ang II by both remaining unblocked ACE and by ACE-independent pathways, 7 whereas ARBs and diuretics increase PRA, Ang I, and Ang II. By contrast, renin inhibitors neutralize any compensatory increase in PRA and prevent the formation of both Ang I and Ang II.…”

mentioning

confidence: 99%

Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker

et al. 2007

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Abstract-Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (nϭ23), ramipril (nϭ21), or irbesartan (nϭ23). In the diuretic combination study, . Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (PϽ0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased ( Key Words: aliskiren Ⅲ ambulatory blood pressure measurement Ⅲ combination therapy Ⅲ hypertension Ⅲ plasma renin activity Ⅲ renin inhibitor Ⅲ renin-angiotensin-aldosterone system A ctivation of the renin-angiotensin (Ang)-aldosterone system (RAAS) plays an important role in the development of hypertension and end-organ damage. 1 Indeed, pretreatment plasma renin activity (PRA) has been shown to be a risk factor for myocardial infarction in hypertensive patients. 2,3 RAAS suppression is, therefore, an important goal of antihypertensive therapy, and RAAS inhibitors, such as Ang-converting enzyme (ACE) inhibitors and Ang receptor blockers (ARBs), have proven to be highly successful treatments for hypertension, heart failure, and related cardiovascular disorders. 4 However, optimized RAAS suppression is difficult to achieve with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate compen-

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“…Suppression of this regulation may compromise renal function. 12 Renal function should be monitored in SN deficiency and OH. 13 L-dihydroxyphenylserine (Droxidopa) used here for treatment is used in patients with dopamine β-hydroxylase deficiency and also, but with weaker pathophysiological rationale, in other forms of OH.…”

Section: Alhenc-gelas Cytochrome B561 and Orthostatism 803mentioning

confidence: 99%

A New Player in Circulatory Adaptation to Orthostatism

Alhenc-Gélas

2018

Circulation Research

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Combined Blockade of the Renin-Angiotensin System With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Antagonists

Cited by 185 publications

References 86 publications

Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study

Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study

Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker

A New Player in Circulatory Adaptation to Orthostatism

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