Dual blockade of the rennin–angiotensin system versus maximal recommended dose of angiotensin II receptor blockade in chronic glomerulonephritis

Mori-Takeyama, Urara; Minatoguchi, Shinya; Murata, Ichijirou; Fujiwara, Hisayoshi; Ozaki, Y.; Ohno, Michiya; Oda, Hiroshi; Ohashi, Hiroshige

doi:10.1007/s10157-007-0013-6

Cited by 10 publications

(3 citation statements)

References 35 publications

(33 reference statements)

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“…Recently, a prospective study of 86 patients with chronic glomerulonephritis compared the effects of candesartan (4–12 mg/day) to its combination at 4 mg/day with benazepril (2.5–10 mg/day) [35]. Despite comparable blood pressure values, dual blockade decreased proteinuria more than single blockade with ARB (–42.3 vs. –60.5%).…”

Section: Are Maximal Monotherapy Doses More Effective Than Dual Blockmentioning

confidence: 99%

Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

Locatelli

Vecchio

Cavalli³

2009

Nephron Clin Pract

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The clinical benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) are well established in chronic kidney disease (CKD) patients with diabetic and non-diabetic nephropathies. But despite appearance, the magnitude of this effect has been questioned particularly in mild, proteinuric nephropathies. Given that the single agents can achieve only partial and not durable suppression of the renin-angiotensin system (RAS), it has been hypothesized that dual blockage with ACE inhibitors and ARBs would be most beneficial in the management of progressive CKD than either agent alone. Available evidence indicates significant anti-proteinuric effect, but long-term data in CKD patients are lacking. Recently, the findings of the ONTARGET trial even questioned the safety of this therapeutic approach. Given that preventing cardiovascular complications is extremely important in CKD and RAS inhibition may be useful in this setting, benefits of RAS blockade must be weighed against its possible adverse effects particularly in elderly patients.

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Section: Are Maximal Monotherapy Doses More Effective Than Dual Blockmentioning

confidence: 99%

Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

Locatelli

Vecchio

Cavalli³

2009

Nephron Clin Pract

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“…La inhibición del SRA produciría incrementos en la secreción de renina y, por lo tanto, de la actividad de la renina plasmática. Algunos estudios han sugerido que valores altos de actividad de renina plasmática se han asociado con mayor incidencia de infarto de miocardio, peor pronóstico de la insuficiencia cardíaca y aumento de la mortalidad cardiovascular, así como empeoramiento de la función renal 37,38 . La aparición de efectos adversos asociados al bloqueo dual del SRA podría suceder en pacientes susceptibles, como por ejemplo aquellos con depleción de volumen y/o sodio ocasionada por un tratamiento intensivo con diuréticos o por una dieta restrictiva en sal, entre otras posibles causas 38,39 .…”

Section: Y Efficacy and Safety Of Aliskiren And Aliskiren/enalapril Cunclassified

Bloqueo dual del sistema renina-angiotensina frente a la monoterapia: revisión sistemática y metaanálisis acumulativo de ensayos clínicos y estudios observacionales

Catalá-López

Saint-Gerons

Honrubia

et al. 2014

Rev. Esp. Salud Publica

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Fundamentos:Trabajos previos han sugerido que el bloqueo dual con inhibidores del sistema renina-angiotensina (SRA) estaría asociado a un incremento de efectos adversos comparado con la monoterapia. Se reexamina la seguridad del doble bloqueo del SRA, especialmente en pacientes de riesgo y se explora la estabilidad de la evidencia acumulada a lo largo de los años.Método: Revisión sistemática con metaanálisis de efectos aleatorios. Se revisaron 15 metaanálisis publicados anteriormente como punto de partida. Se realizó una búsqueda en PubMed/Medline de estudios observacionales y de ensayos clínicos controlados recientes. Las variables dependientes estudiadas fueron: mortalidad (general y cardiovascular), hiperpotasemia, hipotensión, insuficiencia renal, accidente cerebrovascular y la retirada del tratamiento por efectos adversos. Se calcularon los riesgos relativos (RR) y su intervalo de confianza (IC95%)Resultados: El bloqueo dual del SRA no se asoció con una reducción del RR de la mortalidad general (RR:1,00; IC95%: 0,96-1,05; 21 estudios), ni de la mortalidad cardiovascular (RR:1,01; 0,94-1,09; 13 estudios) ni del riesgo de accidente cerebrovascular (RR:1,02; 0,94-1,11; 11 estudios) en comparación con la monoterapia. El bloqueo dual se asoció a un riesgo aumentado de hiperpotasemia (RR:1,58; 1,37-1,81; 34 estudios), hipotensión (RR:1,66; 1,41-1,95; 25 estudios), daño renal (1,52; 1,28-1,81; 29 estudios) y retirada del tratamiento por efectos adversos (RR:1,26; 1,22-1,30; 37 estudios). Los resultados fueron consistentes en las cohortes de pacientes con diabetes mellitus, enfermedad renal o insuficiencia cardiaca.Conclusiones: El bloqueo dual del SRA vs monoterapia incrementa los riesgos de hiperpotasemia, hipotensión, insuficiencia renal e interrupción del tratamiento por efectos adversos. Además no ofrece beneficios adicionales por reducción de la mortalidad general, mortalidad cardiovascular o accidente cerebrovascular. Estos hallazgos son consistentes a lo largo del tiempo. ABSTRACT Risks of Dual Blockade of the ReninAngiotensin System Compared with Monotherapy: A Systematic Review and Cumulative Meta-analysis of Randomized Trials and Observational StudiesBackground: Previous work has suggested that dual blockade using nhibitors of the renin-angiotensin system (RAS) would be associated with n increase in side effects compared to monotherapy. We reexamined the afety of dual RAS blockade, especially in patients at risk, and explored he stability of the evidence accumulated over the years.Method: Systematic review with random-effects meta-analyses. We eviewed 15 previously published meta-analyses as the starting point. Pubed/Medline was searched for recent evidence from both observational nd randomized controlled trials. Outcomes measures were: mortality overall and cardiovascular), hyperkalemia, hypotension, renal failure, troke, and treatment withdrawal due to adverse effects. We calculated elative risks (RR) and confidence intervals (95% CI)Results: Dual RAS blockade was not associated with reduced relative ...

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“…The antiproteinuric effect of an ACE-I-ARB combination implies a synergistic action of these agents that is specific to the intrarenal RAS and occurs at plasma concentrations of ACE-I and ARB below levels affecting systemic BP [Komine et al 2002]. Dual RAS-blockade is clearly considered to decrease proteinuria more than single blockade with an ACE-I or an ARB [Mori-Takeyama et al 2008].…”

Section: Chronic Kidney Diseasementioning

confidence: 99%

ACE-inhibitor, AT₁-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET

Schindler

2008

Therapeutic Advances in Cardiovascular Disease

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Clinical Pharmacology is commonly accepted to be a bridging discipline between basic science observations and clinical practice. Today, it should be a major task of the clinical pharmacologist in academia to provide support in the interpretation of preclinical and clinical study data, to develop evidence-based treatment guidelines and to serve as drug expert supporting all disciplines of clinical medicine with specific pharmacological and therapeutic knowledge. The results of the ONTARGET-trial confront both researchers and clinicians with the unexpected truth that AT(1)-receptor-blockade with an angiotensin-receptor-blocker (ARB) does not seem to have superior therapeutic benefit compared with an ACE-inhibitor (ACE-I) at reducing fatal and nonfatal cardiovascular events. The combination of the two drugs was associated with more adverse events without an increase in benefit. Therefore, the crucial question 'ACE-I, ARB, or both?' requires a new and critical appraisal depending on the medical indication for which these renin-angiotensin-system (RAS)-inhibitors are used: In a population of high-risk patients suffering from cardiovascular disease or diabetes mellitus, the evidence to favor an ARB over an ACE-I is still limited after ONTARGET and because of the higher costs for ARBs one can rather support the old therapeutic advice that ARBs are equally effective as ACE-Is and therefore therapeutic alternatives for patients with ACE-I intolerance. With respect to a very moderate additive BP-lowering effect of dual therapy with an ACE-I and an ARB seen in metaanalysis which was not even clearly attributable to dual RAS-inhibition and the increased adverse event rate in the combination treatment group of ONTARGET, this regimen seems not to be recommendable for the treatment of hypertension. Dual-RAS-blockade using an ACE-I-ARB-combination is an effective therapy to treat proteinuria and might be of therapeutic benefit especially in diabetic patients without concomitant diseases. There may be a therapeutic rationale to prefer ARBs over ACE-Is in well-selected patients with congestive heart failure (CHF) because a considerable amount of angiotensin II (Ang II) is produced independent of angiotensin-conversion-enzyme (ACE) in the failing heart and is therapeutically unaffected by ACE-I treatment. The results of the Val-HeFt and the CHARM-added-study revealed additive effects of an ARB on heart failure related morbidity and mortality when added to existing therapy with an ACE-I suggesting a role for ACE-I-ARB-combination treatment in well selected heart failure patients. Independent of the medical indication for its use, the concept of dual RAS-blockade with an ARB-ACE-I-combination should clinically be used with caution and a close monitoring of potassium levels and kidney function. Although the results of ONTARGET revealed equity of ramipril and telmisartan at reducing fatal and nonfatal cardiovascular events, we should not forget that pharmacologically not all ARBs are the same and the question if the study results of ON...

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Dual blockade of the rennin–angiotensin system versus maximal recommended dose of angiotensin II receptor blockade in chronic glomerulonephritis

Cited by 10 publications

References 35 publications

Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

Bloqueo dual del sistema renina-angiotensina frente a la monoterapia: revisión sistemática y metaanálisis acumulativo de ensayos clínicos y estudios observacionales

ACE-inhibitor, AT₁-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET

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Dual blockade of the rennin–angiotensin system versus maximal recommended dose of angiotensin II receptor blockade in chronic glomerulonephritis

Cited by 10 publications

References 35 publications

Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

Bloqueo dual del sistema renina-angiotensina frente a la monoterapia: revisión sistemática y metaanálisis acumulativo de ensayos clínicos y estudios observacionales

ACE-inhibitor, AT1-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET

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Product

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ACE-inhibitor, AT₁-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET