Clinical outcomes following discontinuation of renin-angiotensin-system inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: a prospective cohort study

Yang, Aimin; Shi, Mai; Lau, Eric S. H.; Wu, Hongjiang; Zhang, Xinge; Fan, Baoqi; Kong, Alice P.S.; Luk, Andrea O. Y.; Ma, Rong; Chan, Juliana C.N.; Chow, Elaine

doi:10.1016/j.eclinm.2022.101751

Cited by 26 publications

(44 citation statements)

References 47 publications

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“…Incident hyperkalemia is associated with increased mortality [1369] and is the most frequent reason for dose reduction or discontinuation of ACEi or ARB administration in CKD patients [1370,1371]. However, reducing the dose or discontinuing RAS blockers has been associated with increased risk of CV events in large surveys [1372][1373][1374] and should be avoided.…”

Section: Special Therapeutic Challengesmentioning

confidence: 99%

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

Chairperson

Co-Chair

Brunström

et al. 2023

Journal of Hypertension

1,136

280

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Document Reviewers: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).

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Section: Special Therapeutic Challengesmentioning

confidence: 99%

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

Chairperson

Co-Chair

Brunström

et al. 2023

Journal of Hypertension

1,136

280

View full text Add to dashboard Cite

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“…Hyperkalemia is one of the adverse events of RAS inhibitors in patients with advanced CKD. The study conducted by Yang et al found that the overall incidence of the first hyperkalemia event was 99.8 per 1000 patient-years [16]. The rates were 101 and 99.6 per 1000 patient-years in the discontinuation and continuation groups respectively.…”

Section: Discussionmentioning

confidence: 98%

“…Sources: References [13][14][15][16] Four studies reported all-cause mortality and according to the pooled results hazard of all-cause mortality was higher in patients in the discontinuation group compared to the continuation group but the difference is statistically insignificant (HR: 1.14, 95% CI: 0.90-1.45) with high heterogeneity among the study results (Isquare: 95%, p-value < 0.00001) as shown in Figure 3.…”

Section: Figure 2: Comparison Of Risk Of Developing Cardiovascular Ev...mentioning

confidence: 99%

Effect of Discontinuation of Renin Angiotensin-System Inhibitors in Patients With Advanced Chronic Kidney Disease: A Meta-Analysis

Naveed¹,

Tirumandyam²,

Mohan³

et al. 2023

Cureus

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Renin-angiotensin system inhibitors (RAS) inhibitors include angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors decrease proteinuria, progression of chronic kidney disease (CKD), and protect against heart failure hospitalizations and cardiovascular events. There is uncertainty about the appropriate time for discontinuing ARB and ACE inhibitor treatment in patients with low estimated glomerular filtration rate (eGFR). In the present meta-analysis, we examined the effect of RAS inhibitor discontinuation on clinical outcomes in patients with advanced CKD compared to the continuation of RAS inhibitors. Two authors conducted electronic database searches in PubMed, the Cochrane Library, and Excerpta Medica Database (EMBASE) for relevant studies published from the inception of the databases to March 15th, 2023, using the following combination of keywords or key terms: "Renin-angiotensinsystem," "angiotensin-converting-enzyme inhibitors", "Angiotensin receptor blockers," and "advanced chronic kidney disease." Primary outcomes assessed in this meta-analysis included cardiovascular events. Secondary outcomes assessed included all-cause mortality and end-stage kidney disease (ESKD). A total of four studies were included in this meta-analysis. The pooled analysis showed that cardiovascular events were significantly higher in patients in the discontinuation group compared to the continuation group (HR: 1.38, 95% CI: 1.21-1.58), ESKD was also significantly higher in the discontinuation group (HR: 1.29, 95% CI: 1.18-1.41). No significant differences were reported between the two groups in all-cause mortality. In conclusion, our meta-analysis provides evidence that continuation of RAS inhibitors could be beneficial in patients with advanced CKD, as it is associated with less risk of cardiovascular events and ESKD.

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“…Our literature search revealed 1,225 nonduplicate articles: 1,166 articles were excluded after the title and abstract were reviewed. After reviewing 59 manuscripts Discontinuation of RAS Inhibitors in Chronic Kidney Disease Am J Nephrol 2023;54:234-244 DOI: 10.1159/000531000 for this meta-analysis, we included 7 articles comprising 8 cohorts that met predefined criteria [10][11][12][16][17][18][19]. The details of the search program in this study are shown in Figure 1.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Discontinuation of Renin-Angiotensin System Inhibitors and Clinical Outcomes in Chronic Kidney Disease: A Systemic Review and Meta-Analysis

Tang¹,

Wen²,

Lv³

et al. 2023

Am J Nephrol

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Background: Discontinuation of renin-angiotensin system (RAS) inhibitors is common in patients with chronic kidney disease (CKD), and the potential danger has been reported in several studies. However, a comprehensive analysis has not been conducted. Objectives: This study sought to evaluate the effects of discontinuation of RAS inhibitors in CKD. Method: Relevant studies up to November 30, 2022, were identified in the PubMed, Embase, Web of Science, and Cochrane Library databases. Efficacy outcomes included the composite of all-cause mortality, cardiovascular events, and end-stage kidney disease (ESKD). Results were combined using a random-effects or fixed-effects model, and sensitivity analysis used the leave-one-out method. Results: Six observational studies and one randomized clinical trial including 244,979 patients met the inclusion criteria. Pooled data demonstrated that discontinuation of RAS inhibitors was associated with an increased risk of all-cause mortality (HR 1.42, 95% CI 1.23–1.63), cardiovascular event risk (HR 1.25, 95% CI 1.17–1.22), and ESKD (HR 1.23, 95% CI 1.02–1.49). In sensitivity analyses, the risk for ESKD was reduced. Subgroup analysis showed that the risk of mortality was more pronounced in patients with eGFR above 30 mL/min/m2 and in patients with hyperkalemia-related discontinuation. In contrast, patients with eGFR below 30 mL/min/m2 were at great risk of cardiovascular events. Conclusions: The discontinuation of RAS inhibitors in patients with CKD was associated with a significantly increased risk of all-cause mortality and cardiovascular events. These data suggest that RAS inhibitors should be continued in CKD if the clinical situation allows.

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Clinical outcomes following discontinuation of renin-angiotensin-system inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: a prospective cohort study

Cited by 26 publications

References 47 publications

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

Effect of Discontinuation of Renin Angiotensin-System Inhibitors in Patients With Advanced Chronic Kidney Disease: A Meta-Analysis

Discontinuation of Renin-Angiotensin System Inhibitors and Clinical Outcomes in Chronic Kidney Disease: A Systemic Review and Meta-Analysis

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