Response by Colin-Ramirez et al to Letter Regarding Article, "Sodium Restriction in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Clinical Trials"

HomeCirculation: Heart FailureVol. 16, No. 3Response by Colin-Ramirez et al to Letter Regarding Article, “Sodium Restriction in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Clinical Trials” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse by Colin-Ramirez et al to Letter Regarding Article, “Sodium Restriction in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Clinical Trials” Eloisa Colin-Ramirez, Nariman Sepehrvand and Justin A. Ezekowitz Eloisa Colin-RamirezEloisa Colin-Ramirez https://orcid.org/0000-0003-2998-1239 Universidad Anáhuac México, Huixquilucan, Estado de México (E.C.-R.). Search for more papers by this author , Nariman SepehrvandNariman Sepehrvand https://orcid.org/0000-0003-0346-3484 Canadian VIGOUR Centre (N.S., J.A.E.), University of Alberta, Edmonton, Canada. Department of Medicine (N.S.), University of Alberta, Edmonton, Canada. Search for more papers by this author and Justin A. EzekowitzJustin A. Ezekowitz https://orcid.org/0000-0002-2724-4086 Canadian VIGOUR Centre (N.S., J.A.E.), University of Alberta, Edmonton, Canada. Division of Cardiology, Department of Medicine (J.A.E.), University of Alberta, Edmonton, Canada. Search for more papers by this author Originally published21 Feb 2023https://doi.org/10.1161/CIRCHEARTFAILURE.122.010420Circulation: Heart Failure. 2023;16Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: February 21, 2023: Ahead of Print In Response:We thank Drs Qiu and Du for their interest in the meta-analysis of randomized controlled trials evaluating the effects of sodium restriction on clinical outcomes in patients with heart failure.1 In this meta-analysis, we reported a neutral effect of sodium restriction on clinical events in heart failure.In their letter to the editor, Qiu and Du2 appropriately noted that the results of our meta-analysis could be limited by the small number of events included in the analysis in assessing the composite outcome of interest (all-cause mortality/hospitalization). They argued that the analysis should have included the data from trials that reported the outcomes of all-cause death or hospitalization individually and should not be limited to the 4 randomized controlled trials that reported this composite outcome. Authors subsequently reported the results of an exploratory analysis that they conducted suggesting a negative impact of sodium restriction on clinical outcomes in heart failure.We appreciate the interest in our study; however, we consider our approach to be valid as per meta-analysis analytical guidelines.3 First, simply pooling death and hospitalization events that occurred in the same trial as separate events may not add up to the number of composite outcomes (as shown in Figure 3 of the SODIUM-HF trial [Study of Dietary Intervention Under 100 mmol in Heart Failure] report).4 To simply combine events in this manner may not be valid, and the authors provided no further methodology in order to verify that their methods account for the numerous issues that can arise. Second, although death, hospitalization, and composite outcomes may have a similar direction and effect size in a hypothetical randomized controlled trial, this might not be necessarily the case in actual trials. In SODIUM-HF, for example, the direction of effect sizes was not aligned between the outcomes of all-cause mortality and the primary outcome (composite of death and cardiovascular hospitalization). Finally, using the data from trials that only reported cardiovascular mortality in lieu of all-cause mortality may predispose the analysis to additional biases since all-cause mortality is not actually measured.In our meta-analysis, we were inclusive and gathered additional data where feasible from individual trials. Maintaining validity is important, and we would advise against the inappropriate pooling of events that are heterogeneous. We note that there is heterogeneity in measured outcomes across the included studies, but also the differences between trials in the level of sodium restriction being tested is one of the major challenges for a meta-analysis. We conducted a subgroup analysis in which we observed that a sodium restriction between 2000 and 3000 mg/d was associated with numerically lower risks of all-cause mortality (odds ratio, 0.59 [95% CI, 0.21–1.65]), when compared with randomized controlled trials with sodium restriction to <2000 mg/d in the intervention arm (odds ratio, 1.11 [95% CI, 0.62–1.97]). We think this may be an important aspect that deserves further consideration in future studies and meta-analyses.Article InformationDisclosures None.FootnotesFor Disclosures, see page 308.References1. Colin-Ramirez E, Sepehrvand N, Rathwell S, Ross H, Escobedo J, Macdonald P, Troughton R, Saldarriaga C, Lanas F, Doughty R, et al. Sodium restriction in patients with heart failure: a systematic review and meta-analysis of randomized clinical trials.Circ Heart Fail. 2022; 16:e009879. doi: 10.1161/CIRCHEARTFAILURE.122.009879LinkGoogle Scholar2. Qiu M, Du L. Letter by Qiu and Du regarding article, “Sodium restriction in patients with heart failure: a systematic review and meta-analysis of randomized clinical trials.”Circ Heart Fail. 2023; 16:e009879. doi: 10.1161/CIRCHEARTFAILURE.122.010356LinkGoogle Scholar3. Deeks JJ, Higgins JPT, Altman DG. In: Chapter 10: analysing data and undertaking meta-analyses. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, eds. Cochrane handbook for systematic reviews of interventions version 6.3. Cochrane; 2022: Available from: www.training.cochrane.org/handbook.Google Scholar4. Ezekowitz JA, Colin-Ramirez E, Ross H, Escobedo J, Macdonald P, Troughton R, Saldarriaga C, Alemayehu W, McAlister FA, Arcand J, et al; SODIUM-HF Investigators. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial.Lancet. 2022; 399:1391–1400. doi: 10.1016/S0140-6736(22)00369-5CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails March 2023Vol 16, Issue 3 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.122.010420PMID: 36802691 Originally publishedFebruary 21, 2023 PDF download Advertisement