Effect of candesartan and lisinopril alone and in combination on blood pressure and microalbuminuria

Morgan, Trefor; Anderson, Adrianne; Bertram, Denise; MacInnis, Robert J.

doi:10.3317/jraas.2004.012

Cited by 33 publications

(19 citation statements)

References 23 publications

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“…Our results indicate the importance of the self-limitation of a single-drug RAS blockade, and this has major consequences for selecting both the timing of drug administration (28) and the daily dosage (7). Besides this physiologic interpretation, intraindividual variations in drug pharmacokinetics may contribute in hypertensive (29) and renal (30) patients to the recruitment of nonresponders by a second blocker acting at another site, within the limits imposed by the variable participation of the RAS in individual BP control (31).…”

Section: Combined Blockade Of the Ras By Aliskiren And Valsartanmentioning

confidence: 85%

Hormonal and Hemodynamic Effects of Aliskiren and Valsartan and Their Combination in Sodium-Replete Normotensive Individuals

Azizi¹,

Ménard²,

Bissery³

et al. 2007

Clinical Journal of the American Society of Nephrology

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Background and Objectives: An AT 1 receptor antagonist induces a counterregulatory renin release whose intensity and duration reflect the magnitude of the renin-angiotensin blockade. We investigated whether a renin inhibitor may neutralize this counterregulation and amplify the effects of AT 1 receptor antagonists.Design, Setting, Participants, & Measurements: In 12 normotensive male individuals who were on a high-sodium diet, a double-blind, placebo-controlled, randomized, crossover design was used to study the hormonal and BP effects of single oral administrations of 300 mg of the renin inhibitor aliskiren, 320 mg of valsartan, and a combination of these two drugs, each at half dosage (150 mg of aliskiren and 160 mg of valsartan).Results: Valsartan (320 mg) increased plasma renin activity and angiotensin I and angiotensin II levels, but 300 mg of aliskiren decreased them for 48 h. Aliskiren (300 mg) stimulated immunoreactive renin release more strongly than 320 mg of valsartan, decreased urinary aldosterone excretion for longer than 320 mg of valsartan, and had a similar BP-lowering effect as 320 mg of valsartan. In combination, 150 mg of aliskiren neutralized the valsartan (160 mg)-induced increase in plasma angiotensins for 48 h. The renin and aldosterone effects of the combination of 150 mg of aliskiren and 160 mg of valsartan were similar to those of 300 mg of aliskiren and greater than those of 320 mg of valsartan. When plasma drug concentrations were taken into account, the combination of 150 mg of aliskiren and 160 mg of valsartan had a synergistic effect on renin release. The BP-lowering effect of 150 mg of aliskiren and 160 mg of valsartan was similar to that of 300 mg of aliskiren and 320 mg of valsartan at peak but was more prolonged.Conclusion: The stronger and longer lasting effects on plasma active renin and urinary aldosterone of aliskiren, alone or in combination, demonstrate a more effective blockade of the renin-angiotensin system than that obtained with 320 mg of valsartan alone.Clin J Am Soc Nephrol 2: 947-955, 2007.

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Section: Combined Blockade Of the Ras By Aliskiren And Valsartanmentioning

confidence: 85%

Hormonal and Hemodynamic Effects of Aliskiren and Valsartan and Their Combination in Sodium-Replete Normotensive Individuals

Azizi¹,

Ménard²,

Bissery³

et al. 2007

Clinical Journal of the American Society of Nephrology

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“…12 Second, Morgan et al found that a combination of candesartan 16 mg plus lisinopril 20 mg (both once daily) had an additive effect on clinic BP only when compared with monotherapy with lisinopril 20 mg, but not when compared with lisinopril 40 mg or candesartan 16 mg or 32 mg. 25 Finally, Forclaz et al have shown, in normotensive individuals, that a supramaximal dose of losartan achieves equivalent RAS inhibition to a combination of losartan plus lisinopril, particularly if the former is administered twice daily. 26 In addition to concerns relating to dosage and dosage intervals, it should be emphasized that these studies were generally of short duration (4 to 8 weeks).…”

Section: Discussionmentioning

confidence: 99%

Systematic Review of Combined Angiotensin-Converting Enzyme Inhibition and Angiotensin Receptor Blockade in Hypertension

2005

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Abstract-Some evidence suggests that long-term angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing angiotensin II levels, which could be inhibited by the addition of an angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an ACE inhibitor and an angiotensin receptor blocker reduced ambulatory blood pressure by 4.7/3.0 mm Hg (95% confidence interval [CI], 2.9 to 6.5/1.6 to 4.3) compared with ACE inhibitor monotherapy and 3.8/2.9 mm Hg (2.4 to 5.3/0.4 to 5.4) compared with angiotensin receptor blocker monotherapy. Clinic blood pressure was reduced by 3.8/2.7 mm Hg (0.9 to 6.7/0.8 to 4.6) and 3.7/2.3 mm Hg (0.4 to 6.9/0.2 to 4.4) compared with ACE inhibitor and angiotensin receptor blocker, respectively. However, the majority of these studies used submaximal doses or once-daily dosing of shorter-acting ACE inhibitors and, when a larger dose of shorter-acting ACE inhibitor was given or a longer-acting ACE inhibitor was used, there was generally no additive effect of the angiotensin receptor blocker on blood pressure. Proteinuria was reduced by the combination compared with ACE inhibitor and angiotensin receptor blocker monotherapy, an effect that was independent of blood pressure in several studies, suggesting that the combination could have benefits in proteinuric nephropathies. None of the studies was of sufficient size and duration to determine whether there may be safety concerns. In conclusion, although there is a small additive effect on blood pressure with an ACE inhibitor-angiotensin receptor blocker combination, the routine use of this combination in uncomplicated hypertension is not recommended until more carefully controlled studies are performed. Key Words: angiotensin-converting enzyme Ⅲ hypertension Ⅲ meta-analysis Ⅲ proteinuria Ⅲ receptors, angiotensin Ⅲ renin-angiotensin system T he renin-angiotensin system (RAS) plays an important role in regulating blood pressure (BP). 1,2 Both angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) inhibit the RAS and have been shown to be effective treatments for increased BP. 3 At the same time, they have other beneficial effects that may be independent of their ability to lower BP, for example, reductions in the progression of nephropathy in diabetes mellitus (DM) and chronic renal failure (CRF). 4 -6 Administration of ACEI causes plasma levels of angiotensin II (Ang II) to become undetectable, whereas there is some evidence that chronic administration of ACEI results in partial escape, ie, there is incomplete suppression of Ang II levels at peak, which may reduce the effectiveness of ACEI as BP-lowering agents. [7][8][9] Several studies have suggested that combining an ARB with an ACEI may provide a more complete blockade of the RAS in the treatment of diabetic and nondiabetic nephropathy and essential hypertension; in particular, it may lower BP and proteinuria furt...

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“…Thus disease was ameliorated, but not prevented. When large clinical trials using Ang II blockade in patients with overt diabetic nephropathy were reported, they too found amelioration but not prevention of nephropathy [6][7][8]. These results in rats and in humans suggested that additional pathways lead to TGF-and PAI-1 production.…”

Section: Introductionmentioning

confidence: 94%

Functional renin receptors in renal mesangial cells

Huang¹,

Border

Noble

2007

Current Science Inc

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Activation of the renin-angiotensin system (RAS) and generation of angiotensin II (Ang II) play a crucial role in fibrotic renal disease beyond this system's hemodynamic actions. Ang II blockade was a great therapeutic breakthrough for renal and cardiovascular diseases; however, this slows, but does not stop, disease progression. These limitations leave other molecules unopposed to sustain disease progression. One is renin, which is markedly elevated by Ang II blockade. Recently, a new renin receptor was cloned in renal mesangial cells. This receptor acts as a renin/prorenin cofactor on the cell surface, enhancing efficiency of angiotensinogen cleavage by renin and unmasking prorenin catalytic activity. Unexpectedly, the receptor induces angiotensin-independent cellular effects in renal mesangial cells, suggesting that renin has novel receptor-mediated actions that could play a role in renal fibrosis. Proof of this could lead to a pharmacological compound blocking renin/prorenin binding and activity as an alternative or adjunct to classical inhibitors of the RAS.

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Effect of candesartan and lisinopril alone and in combination on blood pressure and microalbuminuria

Cited by 33 publications

References 23 publications

Hormonal and Hemodynamic Effects of Aliskiren and Valsartan and Their Combination in Sodium-Replete Normotensive Individuals

Hormonal and Hemodynamic Effects of Aliskiren and Valsartan and Their Combination in Sodium-Replete Normotensive Individuals

Systematic Review of Combined Angiotensin-Converting Enzyme Inhibition and Angiotensin Receptor Blockade in Hypertension

Functional renin receptors in renal mesangial cells

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