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Multicenter Study
. 2024 May;47(5):1372-1379.
doi: 10.1038/s41440-024-01616-8. Epub 2024 Mar 4.

Association between stopping renin-angiotensin system inhibitors immediately before hemodialysis initiation and subsequent cardiovascular events

Yoshihiro Nakamura  1 , Daijo Inaguma  2 , Takahiro Imaizumi  1   3 , Shimon Kurasawa  1 , Manabu Hishida  4 , Masaki Okazaki  1   5 , Yuki Fujishima  1 , Nobuhiro Nishibori  1 , Katsuhiko Suzuki  1 , Yuki Takeda  1 , Shoichi Maruyama  6
Affiliations
Multicenter Study

Association between stopping renin-angiotensin system inhibitors immediately before hemodialysis initiation and subsequent cardiovascular events

Yoshihiro Nakamura et al. Hypertens Res. 2024 May.

Abstract

It is controversial whether renin-angiotensin system inhibitors (RASIs) should be stopped in patients with advanced chronic kidney disease (CKD). Recently, it was reported that stopping RASIs in advanced CKD was associated with increased mortality and cardiovascular (CV) events; however, it remains unclear whether stopping RASIs before dialysis initiation affects clinical outcomes after dialysis, which this study aimed to evaluate. In this multicenter prospective cohort study in Japan, we included 717 patients (mean age, 67 years; 68% male) who had a nephrology care duration ≥90 days, initiated hemodialysis, and used RASIs 3 months before hemodialysis initiation. The multivariable adjusted Cox models were used to compare mortality and CV event risk between 650 (91%) patients who continued RASIs until hemodialysis initiation and 67 (9.3%) patients who stopped RASIs. During a median follow-up period of 3.5 years, 170 (24%) patients died and 228 (32%) experienced CV events. Compared with continuing RASIs, stopping RASIs was unassociated with mortality (adjusted hazard ratio [aHR]: 0.82; 95% confidence interval [CI]: 0.50-1.34) but was associated with higher CV events (aHR: 1.59; 95% CI: 1.06-2.38). Subgroup analyses showed that the risk of stopping RASIs for CV events was particularly high in patients aged <75 years, with a significant interaction between stopping RASIs and age. This study revealed that patients who stopped RASIs immediately before dialysis initiation were associated with subsequent higher CV events. Active screening for CV disease may be especially beneficial for these patients.

Keywords: advanced chronic kidney disease; cardiovascular event; hemodialysis; renin-angiotensin system inhibitors.

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Conflict of interest statement

D.I. has received research funding from The Aichi Kidney Foundation. T.I. has received grants and honoraria from Kyowa Kirin; consulting fees from GlaxoSmithKline. S.M. has received grants and/or research funding from Chugai, Mitsubishi Tanabe, Ono, and ROHTO; honoraria from Alexion, Astellas, AstraZeneca, Bayer, Mitsubishi Tanabe, Kyowa Kirin, and Novartis.

Figures

Fig. 1
Fig. 1
Flow diagram illustrating patient enrollment for the present study. A total of 1118 patients were included in the baseline data (Supplementary Table 1), and 717 in the survival analysis. ACEIs angiotensin-converting enzyme inhibitors, ARBs angiotensin II receptor blockers
Fig. 2
Fig. 2
Time-to-event curves for study outcomes. The outcomes were all-cause death (A) and CV events (B). Stopping RASIs was significantly associated with a higher risk of CV events. RASIs renin-angiotensin system inhibitors, CV cardiovascular
Fig. 3
Fig. 3
Subgroup analyses of CV events. The plots with capped spikes indicate the multivariable-adjusted hazard ratios with 95% confidence intervals for CV events of stopping RASIs compared with continuing RASIs. There was a significant interaction with relatively higher hazard ratios of CV events between stopping RASIs and age (<75 or ≥75 years). CVD cardiovascular disease, CV cardiovascular, RASIs renin-angiotensin system inhibitors
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