Reviews in Cardiovascular Medicine  2020, Vol. 21 Issue (1): 113-118     DOI: 10.31083/j.rcm.2020.01.2 LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials Xiaogen Chen1, †, Chunna Jin1, †, Lan Xie1, Meixiang Xiang1, *() 1Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Key Lab of Cardiovascular Disease of Zhejiang Province, Hangzhou,
Zhejiang 310009, P. R. China Abstract:

Patients with heart failure (HF) are prone to combine with renal insufficiency. Recently, LCZ696 has been used in the treatment of HF, but whether LCZ696 is better than angiotensin converting enzyme inhibitors/angiotensin receptor antagonists (ACEI/ARB) in renal protection for HF patients has not been investigated. Therefore, we conducted a meta-analysis focusing on LCZ696 and its role in preservation of renal function in HF patients. Embase, PubMed, the Cochrane Library and ClinicalTrials.gov databases were electronically searched for available randomized controlled trials (RCTs). HF patients taking LCZ696 or ACEI/ARB were assessed for renal adverse events. The last search date was Sep 20, 2019. A total of 14959 patients from 6 trials were included in this meta-analysis. As compared to ACEI/ARB, LCZ696 significantly reduced the risk of renal function deterioration (odds ratio 0.77, 95% confidence interval 0.61-0.97, P = 0.02). In summary, LCZ696 may have superior renal protection in HF patients compared with ACEI/ARB.

Submitted:  04 January 2020      Accepted:  03 March 2020      Published:  30 March 2020      Fund: 
WKJ-ZJ-1703 to Meixiang Xiang/Provincial and Ministry Joint Major Projects of National Health Commission of China
81700412/National Natural Science Foundation of China *Corresponding Author(s):  Meixiang Xiang     E-mail:  xiangmx@zju.edu.cn About author:  † These authors contributed equally. Service E-mail this article Add to citation manager E-mail Alert RSS Articles by authors Xiaogen Chen    Chunna Jin    Lan Xie    Meixiang Xiang   

Figure 1.  Literature screening flow chart

Table 1.  Baseline Characteristics of Trials included in the Meta-Analysis

Trial
NameNumber of ParticipantsFollow-up
Definition of
decline in
renal functionInclusion criteriaAge(years)Gender
(male)Control groupBaseline
Serum Cr
(mg/dl)Baseline eGFR
(ml/min per
1.73 m ^2)PARAMOUNT-HF (2012)3013monthsScr ≥ 0.5 mg/dL↑ and/or > 25%↑NYHA II-III
HFpEF,
EF ≥ 45%70.9 ± 9.4152 (57%)Valsartan66.5 ± 19.4
VS.
64.3 ± 21.3PARADIGM-HF
(2014)844227monthsend-stage renal disease,
50% ↓GFR,
30 ↓GFR to < 60ml/min.per 1.73 m^2NYHA II-IV,
EF ≤ 40%63.8 ± 11.5
VS.
63.8 ± 11.36567 (78%)Enalapril1.13 ± 0.3
VS.
1.27 ± 0.03PIONEER-HF (2019)8818weeksScr ≥ 0.5 ↑mg/dL (≥ 44 μmol/L) ,
25%↓ GFR.Hemody-namic stabilization after ADHF EF≤40%61 (51-71)
VS. 63 (54-72)635 (72.1%)Enalapril1.28 (1.07-1.51)
VS.
1.27 (1.05-1.50)58.4 (47.5-71.5)
VS.
58.9 (47.4-70.9)EVALUATE-H (2019)46412 weeks.35%↓GFR,
Scr ≥ 0.5 ↑mg/dL AND
25%↓GFRHypertension;
EF ≤ 40% NYHA I-III67.8 (9.8)
VS.
66.7 (8.5)355 (76.5%)Enalapril70 (22)
VS.
69 (20)PRIME (2019)11812monthsSCr ≥ 2.5mg/dL(NYHA) II or III
EF of 25% to < 50% and significant functional MR(64.7 ± 10.2)
VS.
(60.5 ± 11.8)672 (61%)Valsartan(1.00 ± 0.32)
VS
0.98 ± 0.28PARAGONHF (2019)482226monthsdeath from renal failure, end?stage renal disease, or 50% ↓GFRNYHA class II toIV
EF ≥ 45%72.7 ± 8.3
VS.
72.8 ± 8.52317 (48.3%)Valsartan1.1 ± 0.3
VS
1.1 ± 0.3)63 ± 19
VS
62 ± 19

Figure 2.  Forest plot of worsening renal function comparison: LCZ696 group vs ACEI/ARB group

Figure 3.  Forest map of 6 RCTs

Figure 4.  Forest plot of worsening renal function comparison: LCZ696 group vs ACEI/ARB group afterexcluding the PIONEER-HF

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