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      Effect of Renin−Angiotensin−Aldosterone System Blockade on Outcomes in Patients With ESRD: A Prospective Cohort Study in Korea

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          Abstract

          Introduction

          Conflicting results still exist regarding the benefit of renin−angiotensin−aldosterone system (RAAS) blockade on clinical outcomes in dialysis patients. The aim of this study was to evaluate the effects of RAAS blockade on survival in Korean patients with end-stage renal disease (ESRD).

          Methods

          Our analysis was based on the data of 5223 patients enrolled from the Clinical Research Center for ESRD, a nationwide prospective observational cohort. Multivariate Cox regression was applied for risk factor analysis with the cumulative duration of RAAS blockade use as time-varying covariate. The risks for mortality from all causes and major cardiovascular event−free survival were estimated.

          Results

          Compared to the control group, patients in the RAAS group were younger but had a higher proportion of diabetes mellitus, had higher systolic blood pressure, required a greater number of prescribed antihypertensive drugs, and had a longer dialysis duration. On multivariate time-varying Cox regression analysis, the RAAS group with cumulative duration of >90 days was significantly associated with a lower risk of mortality from all causes after adjustment for confounding (hazard ratio [HR] = 0.45, 95% confidence interval [CI] = 0.35–0.58, P < 0.0001). Major cardiovascular event−free survival was also better for the RAAS group than for the control group on multivariate analysis (HR = 0.27, 95% CI = 0.20–0.37, P < 0.0001), considering the cumulative duration of RAAS blockade use.

          Conclusion

          In Korean patients with ESRD, we reported a specific benefit of RAAS blockade in improving overall survival after adjustment for confounding factors from real-world data.

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          Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO).

          Charles Herzog, Richard W Asinger, Alan K Berger … (2011)
          Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes.
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            Use of statins and the risk of death in patients with prostate cancer.

            Oriana HY Yu, Maria Eberg, Serge Benayoun … (2014)
            To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.
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              Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis.

              Jun Cheng, Jianghua Chen, Xiayu Li … (2014)
              Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may have different effects on cardiovascular (CV) events in patients with diabetes mellitus (DM). To conduct a meta-analysis to separately evaluate the effects of ACEIs and ARBs on all-cause mortality, CV deaths, and major CV events in patients with DM. DATA SOURCES Data sources included MEDLINE (1966-2012), EMBASE (1988-2012), the Cochrane Central Register of Controlled Trials, conference proceedings, and article reference lists. We included randomized clinical trials reporting the effects of ACEI and ARB regimens for DM on all-cause mortality, CV deaths, and major CV events with an observation period of at least 12 months. Studies were excluded if they were crossover trials. Dichotomous outcome data from individual trials were analyzed using the risk ratio (RR) measure and its 95% CI with random-effects models. We estimated the difference between the estimates of the subgroups according to tests for interaction. We performed meta-regression analyses to identify sources of heterogeneity. Primary end points were all-cause mortality and death from CV causes. Secondary end points were the effects of ACEIs and ARBs on major CV events. Twenty-three of 35 identified trials compared ACEIs with placebo or active drugs (32,827 patients) and 13 compared ARBs with no therapy (controls) (23,867 patients). When compared with controls (placebo/active treatment), ACEIs significantly reduced the risk of all-cause mortality by 13% (RR, 0.87; 95% CI, 0.78-0.98), CV deaths by 17% (0.83; 0.70-0.99), and major CV events by 14% (0.86; 0.77-0.95), including myocardial infarction by 21% (0.79; 0.65-0.95) and heart failure by 19% (0.81; 0.71-0.93). Treatment with ARBs did not significantly affect all-cause mortality (RR, 0.94; 95% CI, 0.82-1.08), CV death rate (1.21; 0.81-1.80), and major CV events (0.94; 0.85-1.01) with the exception of heart failure (0.70; 0.59-0.82). Both ACEIs and ARBs were not associated with a decrease in the risk for stroke in patients with DM. Meta-regression analysis showed that the ACEI treatment effect on all-cause mortality and CV death did not vary significantly with the starting baseline blood pressure and proteinuria of the trial participants and the type of ACEI and DM. Angiotensin-converting enzyme inhibitors reduced all-cause mortality, CV mortality, and major CV events in patients with DM, whereas ARBs had no benefits on these outcomes. Thus, ACEIs should be considered as first-line therapy to limit excess mortality and morbidity in this population.
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                Author and article information

                Contributors
                Jung Pyo Lee
                Journal
                Journal ID (nlm-ta): Kidney Int Rep
                Journal ID (iso-abbrev): Kidney Int Rep
                Title: Kidney International Reports
                Publisher: Elsevier
                ISSN (Electronic): 2468-0249
                Publication date PMC-release: 04 August 2018
                Publication date Collection: November 2018
                Publication date (Electronic): 04 August 2018
                Volume: 3
                Issue: 6
                Pages: 1385-1393
                Affiliations
                [1 ]Department of Internal Medicine, Dongguk University Gyeongju Hospital, Dongguk University College of Medicine, Gyeongju, Korea
                [2 ]Institute of Life and Death Studies, Hallym University, Chuncheon, Korea
                [3 ]Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea
                [4 ]Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
                [5 ]Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
                [6 ]Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
                [7 ]Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
                [8 ]Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
                Author notes
                [∗ ] Correspondence: Jung Pyo Lee, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 156-707, Korea. nephrolee@ 123456gmail.com
                [9]

                These authors contributed equally to this work.

                Article
                Publisher ID: S2468-0249(18)30175-X
                DOI: 10.1016/j.ekir.2018.07.023
                PMC ID: 6224622
                SO-VID: 7dc16a42-826a-4a5a-9de5-297b3f88f2dd
                Copyright © © 2018 International Society of Nephrology. Published by Elsevier Inc.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 18 December 2017
                Date revision received : 28 July 2018
                Date accepted : 30 July 2018
                Categories
                Subject: Clinical Research

                Keywords: ace inhibitor,arb,dialysis,esrd,mortality
                Data availability:
                Keywords: ace inhibitor, arb, dialysis, esrd, mortality

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