Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial

Bhandari, Sunil; Ives, Natalie; Brettell, Elizabeth; Valente, Marie; Cockwell, Paul; Topham, Peter; Cleland, John G.F.; Khwaja, Arif; Nahas, Meguid El

doi:10.1093/ndt/gfv346

Cited by 83 publications

(79 citation statements)

References 44 publications

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“…One possible explanation is that ACEIs/ARBs may have been discontinued in the late stages of non-dialysis-dependent CKD due to hyperkalemia and concerns about decreased eGFR, and never restarted once the patient transitioned to PD. Indeed, there is an ongoing multicenter randomized controlled trial of ACEI/ARB withdrawal in patients with Stage 4 or 5 CKD that stemmed from such concerns [55]. Clinicians should not shy away from restarting ACEIs/ARBs in incident PD patients since they are much more likely to exhibit hypokalemia than hyperkalemia due to the continuous nature of the dialysis.…”

Section: Table1 Continuedmentioning

confidence: 99%

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis

Shen

Saxena

Montez‐Rath

et al. 2016

Nephrol. Dial. Transplant.

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A B S T R A C TBackground: Data on the effectiveness of angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in reducing cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD) are limited. We investigated the association between ACEI/ARB use and CV outcomes in patients initiating PD. Methods: In this observational cohort study, we identified from the United States Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We applied Cox regression to an inverse probability of treatment weighted cohort to estimate the hazard ratios (HRs) for the combined outcome of death, ischemic stroke or myocardial infarction (MI) and each outcome individually. Results: Among 4879 patients, 2063 (42%) used an ACEI/ARB. Patients were followed up for a median of 1.2 years. We recorded 1771 events, for a composite rate of 25 events per 100 person-years. ACEI/ARB use (versus nonuse) was associated with a reduced risk of the composite outcome {HR 0.84 [95% confidence interval (CI) 0.76-0.93]}, all-cause mortality ] and CV death ], but not MI )] or ischemic stroke [HR 1.06 (95% CI 0.79-1.43)]. Results were similar in astreated analyses. In a subgroup analysis, we did not find any effect modification by residual renal function. Conclusions: ACEI/ARB use is common in patients initiating PD and is associated with a lower risk of fatal CV outcomes.

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Section: Table1 Continuedmentioning

confidence: 99%

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis

Shen

Saxena

Montez‐Rath

et al. 2016

Nephrol. Dial. Transplant.

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“…Some other investigators around the world have shown similar reports raising concerns about the potential nephrotoxicity of angiotensin blockade especially in the elderly (>65-year old) with more advanced CKD (13)(14)(15). As a result of these legitimate concerns, we now have a randomized controlled trial to determine whether the pre-emptive withdrawal of ACEI/ARB in patients with advanced CKD would result in improved cardiorenal outcomes -the ongoing STOP ACEi Trial (16,17). The second case report presented above demonstrated the syndrome of rapid onset ESRD, or SORO-ESRD, that is to say, acute yet irreversible renal failure requiring permanent RRT including kidney transplantation where applicable (7)(8)(9)(10).…”

Section: Discussionmentioning

confidence: 81%

Late onset renal failure from angiotensin blockade (LORFFAB) and the syndrome of rapid onset endstage renal disease (SORO-ESRD) revisited – Two case reports from Mayo Clinic Health System, Northwestern Wisconsin, USA; a review paper

Onuigbo¹,

Samuel²,

Agbasi³

2018

J Renal Inj Prev

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In 2005, we had described for the first time, the syndrome of late onset renal failure from angiotensin blockade (LORFFAB), represented by the observed accelerated loss of kidney function in patients on a priori stable doses of an angiotensin converting enzyme inhibitor and/or an angiotensin receptor blocker, for more than three months, with this acute kidney injury (AKI) occurring despite the absence of any identifiable known precipitating factors. Moreover, in 2010, we had described the syndrome of rapid onset end-stage renal disease (SORO-ESRD), represented by acute yet irreversible renal failure following medical illness or surgical procedures, again sometimes in association with concurrent angiotensin blockade. In this article, we describe two representative case reports, one each of both syndromes, and discuss the implications of LORFFAB and SORO-ESRD in current nephrology practice paradigms.Please cite this paper as: Onuigbo M, Samuel E, Agbasi N. Late onset renal failure from angiotensin blockade (LORFFAB) and the syndrome of rapid onset end-stage renal disease (SORO-ESRD) revisited -Two case reports from Mayo Clinic Health System, Northwestern Wisconsin, USA; a review paper. J Renal Inj Prev. 2018;7(2):58-63. DOI: 10.15171/jrip.2018.15. In 2005, we described for the first time, the syndrome of late onset renal failure from angiotensin blockade (LORFFAB). This is accelerated loss of kidney function in patients on a priori stable doses of an angiotensin converting enzyme inhibitor and/or an angiotensin receptor blocker (ARB), for more than 3 months, with this acute kidney injury (AKI) occurring in the absence of any identifiable known precipitating factors. Moreover, in 2010, we described the syndrome of rapid onset end-stage renal disease (SORO-ESRD). This is acute yet irreversible renal failure following medical illness or surgical procedures, again sometimes in association with concurrent angiotensin blockade. In this article, we describe two representative case reports, one case for LORFFAB and another case for SORO-ESRD and subsequently discuss the implications of LORFFAB and SORO-ESRD in current nephrology practice paradigms. Whereas we support the consensus that angiotensin blockade, for now, remains the mainstay of renoprotection, we however must draw attention to the potential for nephrotoxicity from angiotensin blockade under certain clinical scenarios including the ones described here and more. The association of LORFFAB and SORO-ESRD demands further investigation.

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“…Recent cardiovascular guidelines have recommended caution with the use of ACEi/ARBs for patients with HF and advanced CKD [23]. The potential merits and risks of ACEi/ARB use in advanced CKD is in a state of equipoise and has formed the basis for the current UK-based STOP-ACEi trial, a randomised controlled open label study of ACEi/ARB withdrawal in progressive and advanced CKD [24]. The results of this trial could be critical to delaying the need for expensive and invasive dialysis therapy without being a detriment to other outcomes such as cardiovascular events [25].…”

Section: Uncertainty In the Use Of Acei/arbs In Advanced Ckdmentioning

confidence: 99%

“…Adequately powered randomised control trials to elucidate a potential benefit from cessation of ACEi/ARBs in patients with advanced CKD would be of enormous value to guide optimal clinical practice and delay renal progression and the need for RRT. This has formed the basis for the STOP ACEi trial [24,] but should this apply to all high-risk groups?…”

Section: What Happens To Individuals With Ckd and Proteinuria?mentioning

confidence: 99%

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Should We STOP Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Advanced Kidney Disease?

Ahmed

Jorna²,

Bhandari³

2016

Nephron

Self Cite

8,329

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Chronic kidney disease (CKD) is a worldwide public health problem associated with a high prevalence of cardiovascular disease (CVD) and impaired quality of life. Previous research for preventing loss of glomerular filtration rate (GFR) has focused on reducing blood pressure (BP) and proteinuria. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (ARB) are commonly used in patients with early CKD, but their value in advanced CKD (estimated GFR (eGFR) ≤30 ml/min/1.73 m²) is unknown. There remains a debate about the omission of ACEi/ARB in patients with advanced CKD and their use in association with CVD or heart failure. Does the potential gain in eGFR with ACEi/ARB cessation outweigh the potential adverse cardiovascular outcomes? This paper reviews the current literature that addresses this issue. Several controversies are discussed. Although lowering BP reduces cardiovascular events, evidence suggests that ACEi/ARBs are not superior to other antihypertensive agents. There are no studies assessing the benefits of ACEi/ARB therapy in cardiovascular risk reduction in advanced non-dialysis CKD. The STOP ACEi trial will strengthen the evidence base and shed light on the potential merits and dangers of ACEi/ARB use in advanced CKD on renal function and cardiovascular outcomes.

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Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial

Cited by 83 publications

References 44 publications

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis

Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis

Late onset renal failure from angiotensin blockade (LORFFAB) and the syndrome of rapid onset endstage renal disease (SORO-ESRD) revisited – Two case reports from Mayo Clinic Health System, Northwestern Wisconsin, USA; a review paper

Should We STOP Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Advanced Kidney Disease?

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