Supplementary file 1_Probiotics and synbiotics as adjunctive therapies for heart failure: a systematic review with network and pairwise meta-analyses.docx

The revision-stage search audit identified no additional eligible randomized trials and no eligible prebiotic-only trials. Across all the trial populations, 1,021 participants were randomized, 973 of whom were allocated to review-eligible arms. The left ventricular ejection fraction (LVEF) network included 7 studies and 539 participants in the analysis set; however, this network was star-shaped, had no closed loops, and depended on a combined comparator node.

The exploratory NMA estimate for multi-strain bacterial probiotics versus the combined comparator was a mean difference (MD) of 2.13 percentage points (95% confidence interval [CI] −0.10 to 4.35). The comparator-stratified sensitivity analysis for usual care yielded an MD of 1.83 percentage points (95% CI −2.33 to 5.98). All synthesized results were assessed as having either some concern or a high risk of bias.

The effect estimates were generally imprecise, and the certainty of evidence was low or very low. Adverse event definitions and denominators were inconsistent.</p>Conclusion<p>The available evidence is sparse and affected by significant non-transitivity, risk of bias, and imprecision. Network comparisons and rankings should be considered hypothesis-generating; therefore, no probiotic or synbiotic adjunct can be recommended for routine HF management.</p>Systematic review registration<p>CRD420261413595.

Public URL: crd.york.ac.uk/PROSPERO/view/CRD420261413595.</p>