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

Hypertension Research https://doi.org/10.1038/s41440-024-01616-8 ARTICLE Association between stopping renin-angiotensin system inhibitors immediately before hemodialysis initiation and subsequent cardiovascular events Yoshihiro Nakamura1 Daijo Inaguma2 Takahiro Imaizumi1,3 Shimon Kurasawa1 Manabu Hishida4 Masaki Okazaki1,5 Yuki Fujishima1 Nobuhiro Nishibori1 Katsuhiko Suzuki1 Yuki Takeda1 Shoichi Maruyama1 ● ● ● ● ● ● ● ● ● ● 1234567890();,: 1234567890();,: Received: 13 October 2023 / Revised: 9 January 2024 / Accepted: 27 January 2024 © The Author(s) 2024. This article is published with open access 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 ● Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41440024-01616-8. * Shoichi Maruyama 1 Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 4668550, Japan 2 Department of Internal Medicine, Fujita Health University Bantane Hospital, 3-6-10, Otobashi, Nakagawa-ku, Nagoya, Aichi 454-8509, Japan 3 Department of Advanced Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan 4 Department of Nephrology, Kaikoukai Josai Hospital, Nagoya, Japan, 4-1, Kitahata-cho, Nakamura-ku, Nagoya, Aichi 453-0815, Japan 5 Department of Clinical Research Education, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan ● ● Introduction Chronic kidney disease (CKD) patients are at higher risk for cardiovascular (CV) events and mortality than the general population and require optimal management to reduce these risks [1, 2]. Renin-angiotensin system inhibitors (RASIs) have been reported to reduce the risk of kidney failure, CV events, and all-cause mortality in patients with CKD [3]. Thus, guidelines recommend using RASIs for advanced CKD (i.e., CKD stage 4 or 5) unless they are intolerable due to hyperkalemia or worsening of kidney function. However, the benefits of using RASIs for advanced CKD are less certain because most clinical trials excluded participants with advanced CKD [2, 4–6]. Several studies investigated whether RASIs should be stopped or continued in patients with advanced CKD [7–13]. Stopping RASIs in patients with advanced CKD was associated with all-cause mortality [8, 9] and CV events Y. Nakamura et al. Graphical Abstract [8, 9, 11]. However, the observational period of these studies was until the initiation of dialysis; thus, whether stopping RASIs before dialysis initiation affects prognosis after the initiation of dialysis is uncertain. This study aimed to evaluate whether stopping RASIs immediately before dialysis initiation affects subsequent outcomes, such as mortality and CV events, in patients registered with the Aichi cohort study of the prognosis in patients newly initiated into dialysis (AICOPP), which is a multicenter, prospective cohort study. Materials and methods Study population We used data from the AICOPP, including 1520 incident dialysis patients. Details of the AICOPP have been previously described [14]. The cohort included patients who initiated dialysis between October 2011 and September 2013 at 17 facilities in Aichi, Japan. We screened patients aged ≥20 years and enrolled those who were discharged alive after hospitalization for dialysis initiation. Written informed consent was obtained from all patients. In our study of patients registered with AICOPP, we excluded patients referred to nephrologists <90 days prior to dialysis initiation or whose duration of nephrologist care was unknown, and patients who opted for peritoneal dialysis. We recruited patients who had used angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) 3 months prior to hemodialysis (HD) initiation and those who had data of ACEIs or ARBs at the time of HD initiation for survival analysis. Baseline variables Baseline demographic and clinical data, including blood and urine test results, were collected immediately before or during hospitalization for HD initiation. Body mass index (BMI) was calculated using the following formula: BMI = weight(kg)/height(m)2. Diabetes mellitus was defined as fasting blood glucose ≥126 mg/dL, casual blood glucose ≥200 mg/dL, HbA1c (NGSP) ≥ 6.5%, use of insulin, or use of oral hypoglycemic agents. A history of CV disease (CVD) was defined as a history of heart failure requiring hospitalization, coronary artery intervention, heart bypass surgery, stroke, aortic disease requiring surgery, or peripheral artery disease requiring hospitalization. Urgent dialysis was defined as emergency dialysis or dialysis initiation using an indwelling vascular catheter when faced with a risk to life. Emergency dialysis initiation was referred to as unscheduled initiation. The estimated glomerular filtration rate (eGFR) was calculated using the Japanese Society of Nephrology’s equation: eGFR = 194 × serum creatinine–1.094 × age–0.287 (×0.739 for women). The use of diuretics before dialysis initiation included regular loop Association between stopping renin-angiotensin system inhibitors immediately before hemodialysis. . . diuretics, thiazide-type diuretics, or spironolactone [14, 15]. T (...truncated)