Dual Renin-Angiotensin-Aldosterone Blockade: Promises and Pitfalls

Chrysant, Steven G.; Chrysant, George S.

doi:10.1007/s11906-014-0511-3

Cited by 9 publications

(7 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, several clinical trials (ONTARGET, ALTITUDE and VA NEPHRON-D) in patients with hypertension, heart failure, and chronic kidney disease with proteinuria have demonstrated no beneficial effects of dual versus single RAAS blockade, but a higher incidence of adverse events. 130 Some new combined agents affecting RAAS occurred recently. According to the latest network meta-analysis of Xie et al., ARNI, a novel dual-acting angiotensin receptor-neprilysin inhibitor has the highest probability of being the most effective therapy for heart failure and reduced ejection fraction compared to ACE-Is and/or ARBs.…”

Section: Combined Treatment—another Approach To Raas Blockingmentioning

confidence: 99%

New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

Gromotowicz-Popławska

Szoka

Kołodziejczyk

et al. 2016

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT 1 receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT 1 axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders.

show abstract

Section: Combined Treatment—another Approach To Raas Blockingmentioning

confidence: 99%

New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

Gromotowicz-Popławska

Szoka

Kołodziejczyk

et al. 2016

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…Based on the current evidence, many investigators no longer recommend the routine use of dual RAAS blockade for the treatment of hypertension or chronic kidney disease, except for the presence of HF with reduced EF or DN with proteinuria [8].…”

Section: Discussionmentioning

confidence: 99%

“…The latest research demonstrates that the long-held belief that a more complete blockade of RAAS, with a combination of two of the three existing RAAS blockers (ACE inhibitors (ACEi), ARBs, or DRIs), has come under serious doubt regarding its effectiveness and safety for the treatment of patients with hypertension, or nephropathy with proteinuria [8]. With regards to clinical studies, it was concluded that, in human diseases, there are currently no proven benefits of the combined ACEi and ARB over single drug RAAS blockade.…”

Section: Contrasting Evidence On the Dual Raas Blockadementioning

confidence: 99%

A Dose Response Analysis of Dual Renin Angiotensin Aldosterone System (RAAS) Blockade Among Diabetic Nephropathy Patients with Albuminuria and Proteinuria: A Meta-Analysis

Dalbhi¹,

Eissa²,

Kayid³

et al. 2019

Diabetes Complications

View full text Add to dashboard Cite

Objective: Treatment with renin angiotensin aldosterone system (RAAS) blockade including angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) have been shown to improve clinical outcomes. However, recent contrasting evidence regarding the dual RAAS blockade has also been presented. Very few studies have investigated the effectiveness of this dual blockade among diabetic nephropathy (DN) patients in association with albuminuria or proteinuria. Research Design and Methods: A review of randomized controlled trial (RCT) studies (n=45) reporting on the dose response analysis among DN patients using the RAAS blockade (including both ACEi and ARBs and other combinations) and other monotherapies over a 25-year period was performed. Overall, 45 studies of DN patients (n=18,628) with albuminuria or proteinuria were included. Results: An association between dual RAAS blockade and DN was observed, in which 18 of the 45 datasets revealed that combination therapies were effective among DN patients. Although there was a decline in albuminuria (mean difference:-19.93 mcg/L; 95% CI-50.32-10.47; I2 = 87.8%, p = 0.000) and a slight decline in proteinuria (mean difference:-0.19 mg/mmol; 95% CI-2.32-2.70; I2 = 99.2%, p = 0.000) with dual RAAS blockade combination therapy, these results demonstrated high heterogeneity among studies, with non-significant effects. Conclusion: Based on this study, it appears that dual RAAS blockade (or a combination of therapies) is a neutral treatment for patients with DN presenting with symptoms of albuminuria and/or proteinuria. Therefore, other factors must be considered when recommending therapies for DN patients.

show abstract

“…Recently Chrysant and Chrysant (2015), based on the evidences available suggested that dual RAS blockade should not be a routine treatment for cardiovascular disorders, but included as reasonable indications for dual-blocking diabetic nephropathy with proteinuria and heart failure with reduced ejection fraction.…”

Section: Combination Therapy In Ckdmentioning

confidence: 99%

Combination therapy in chronic kidney disease?

Juncos¹,

Joaquin²

2015

Therapeutic Advances in Cardiovascular Disease

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) plays a fundamental role in preserving the circulation and yet, it may be injurious to heart and blood vessels and may also allow, and sometimes hasten, kidney disease progression. Thus, effective RAS inhibition may be a major pharmacologic necessity to control hypertension, to decrease cardiovascular complication, and to inhibit kidney disease progression. Unfortunately, the beneficial effects attained in the management of renal disease sometimes are incomplete. The reasons for these inadequate outcomes may include angiotensin escape or excessive local angiotensin production. Two pharmacologic strategies have been proposed to overcome this drawback including higher than recommended doses of RAS inhibitors and the combination of two different RAS inhibitors. However, three large studies have shown that these more intensive pharmacologic approaches should be treated with caution when applied to high-risk patients, as organ perfusion may fall to critical levels that may cause severe complications. Nevertheless, intensive RAS inhibition (including combination therapy) may be the sole alternative in patients with chronic kidney disease (CKD) in whom other therapeutics options have failed. In these cases, adequate precautions including close clinical and laboratory follow up should prevent major complications.

show abstract

Dual Renin-Angiotensin-Aldosterone Blockade: Promises and Pitfalls

Cited by 9 publications

References 67 publications

New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

A Dose Response Analysis of Dual Renin Angiotensin Aldosterone System (RAAS) Blockade Among Diabetic Nephropathy Patients with Albuminuria and Proteinuria: A Meta-Analysis

Combination therapy in chronic kidney disease?

Contact Info

Product

Resources

About