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Abstract
Background Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost.
Objective We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies.
Methods Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label.
Results Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: −0.44 (95% CI −0.49 to −0.39), 6 min walk distance (mean difference: +109 m (95% CI 105 to 114 m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy.
Conclusions Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.
- Heart Failure, Diastolic
- Heart Failure, Systolic
- Pharmacology
- Meta-Analysis
Data availability statement
Upon reasonable request datasets generated for this systematic review can be shared.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
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Data availability statement
Upon reasonable request datasets generated for this systematic review can be shared.
Supplementary materials
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Footnotes
X @MLHandoko
SN and AAVdB contributed equally.
Contributors SN, AAVdB, FdM, SR and MLH contributed to the conception and design of the manuscript; SN, AAVdB, OS and MLH were responsible for data acquisition, while SR, FdM and MLH performed statistical analysis and interpretation of the data; SN, AAVdB and MLH drafted the manuscript, which was critically reviewed by OS, SR and FdM; all the authors approved the final version of the manuscript and accept accountability for the accuracy and integrity of the work. MLH, as the guarantor, accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Funding FdM is supported by the Netherlands CardioVascular Research Initiative (CVON 2018-29:PHAEDRA-IMPACT and 2017-10:Dolphin-Genesis). FdM is further supported by The Netherlands Organisation for Scientific Research (NWO-VIDI: 917.18.338) and the Dutch Heart Foundation (DHF Dekker Senior Post-Doc Grant 2018T059). MLH is supported by the Dutch Heart Foundation (dr. E.Dekker Senior Clinical Scientist Grant 2020T058) and CVON (2020B008RECONNEXT).
Competing interests FdM received research funding from Janssen and BIAL. MLH received an investigator-initiated research grant of Vifor Pharma, an educational grant of Boehringer Ingelheim and Novartis, and speaker/consultancy fees of Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, MSD, Novartis, Sankyo, Dayichi, Quin, Vifor Pharma; all not related to this study. All other authors have no potential conflicts of interest to report.
Provenance and peer review Not commissioned; externally peer reviewed.
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