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Combined blockade of renin-angiotensin-aldosterone system reduced all-cause but not cardiovascular mortality in dialysis patients: A mediation analysis and systematic review

  • Author Footnotes
    1 These authors contributed equally to this work.
    Shao-Min Li
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China

    Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 China

    Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Wan-Bing He
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China

    Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Jie Chen
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China

    Radiotherapy Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
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  • Qing-Qing Cai
    Affiliations
    Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060 China
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  • Fei-Fei Huang
    Affiliations
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China

    Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China
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  • Kun Zhang
    Affiliations
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China

    Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China
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  • Jing-Feng Wang
    Affiliations
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China

    Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China
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  • Xun Liu
    Correspondence
    Corresponding author. Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
    Affiliations
    Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 China
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  • Hui Huang
    Correspondence
    Corresponding author. Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, 107 West Yanjiang Road, Guangzhou 510120, China.
    Affiliations
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China

    Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120 China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • Effect of combined RAAS blockade was firstly evaluated in dialysis patients.
      • Combined RAAS blockade reduced all-cause but not cardiovascular mortality.
      • Hypotension mediated effect of combined RAAS blockade on cardiovascular mortality.

      Abstract

      Background and aims

      Full blockade of renin-angiotensin-aldosterone system (RAAS) is believed to decrease morbidity and mortality of patients with chronic kidney disease. In non-dialysis patients, combined RAAS blockade with two different RAAS blockers causes more adverse events without improving survival, but its role in maintenance dialysis patients is still unclear. We conducted a systematic review and mediation analysis to investigate the efficacy and safety of combined RAAS blockade in dialysis patients.

      Methods

      Comprehensive search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library database to June 2017 to identify relevant studies. Studies comparing combined with single RAAS blockade and reporting all-cause death, cardiovascular death, hypotension or hyperkalemia in dialysis patients were included. Effect sizes were calculated with randomized effects model and summarized as odd ratios (OR).

      Results

      A total of 9 studies with 13,050 dialysis patients were included. Compared with single blockade, combined blockade significantly reduced all-cause mortality (OR 0.71, 95% confidence interval 0.54–0.93, p = 0.01), while cardiovascular mortality remained unchanged (0.85, 0.45–1.59, p = 0.61). Combined blockade tended to increase odd of hypotension but not odd of hyperkalemia (1.54, 1.00–2.38, p = 0.05; 0.89, 0.76–1.05, p = 0.17). Further mediation analysis indicated that hypotension might exert a suppression effect on the survival benefit of angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker treatment on cardiovascular mortality.

      Conclusions

      Combined RAAS blockade might be a promising treatment in dialysis patients to further reduce mortality if blood pressure was well controlled.

      Keywords

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