ArticleJHLT open2026
Efficacy and safety of everolimus in heart transplant recipients: A meta-analysis.
Article in JHLT open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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7 authors.
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Abstract
Background: Long-term outcomes after heart transplantation remain limited by cardiac allograft vasculopathy (CAV) and calcineurin inhibitor (CNI)-related nephrotoxicity. Everolimus has emerged as a CNI-sparing strategy, yet its net clinical benefit remains debated. Objectives: To determine whether everolimus-based immunosuppression improves efficacy and safety compared with standard CNI-based therapy in heart transplant recipients. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials and comparative observational studies enrolling adult and/or pediatric heart transplant recipients. MEDLINE, EMBASE, and CENTRAL were searched from inception. The primary endpoint was the composite MATE-3 (acute rejection, CAV, or chronic kidney disease). Secondary outcomes included mortality, individual efficacy components, renal function, and the broader safety composite (MATE-6). Pooled effect estimates were generated using random-effects models. Results: Sixty studies including 1786 heart transplant recipients (mean age ≈52 years) were analyzed. Everolimus-based regimens reduced cardiac allograft vasculopathy progression by intravascular ultrasound (RR ≈0.57) and improved renal function when combined with CNI minimization (mean eGFR increase ≈10-15 mL/min). The composite MATE-3 endpoint favored everolimus. All-cause mortality was neutral (RR ≈0.98). Acute rejection varied by protocol, with higher rates mainly in strategies involving abrupt or late CNI withdrawal. The safety composite (MATE-6) showed increased adverse events and treatment discontinuation with everolimus.Sixty studies were included. Everolimus-based regimens significantly reduced CAV progression by intravascular ultrasound and consistently preserved renal function when coupled with CNI minimization. The composite MATE-3 endpoint favored everolimus, driven by robust vascular and renal protection. Importantly, all-cause mortality was neutral, confirming that CNI reduction with everolimus does not compromise survival. Acute rejection demonstrated protocol-dependent variability, with excess risk observed primarily in strategies involving abrupt or late CNI withdrawal. The safety composite (MATE-6) revealed higher rates of drug discontinuation and adverse events, underscoring the need for careful monitoring. Conclusions: Everolimus-based immunosuppression provides meaningful vasculoprotection and renal preservation without increasing mortality. When used within structured CNI minimization protocols, it offers a strategy to improve long-term graft health after heart transplantation. Careful and individualized use is essential to balance efficacy and tolerability.
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