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Trimetazidine improves exercise tolerance in patients with ischemic heart disease

A meta-analysis

Verbesserung der Belastungstoleranz durch Trimetazidin bei Patienten mit ischämischer Herzerkrankung

Eine Metaanalyse

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Abstract

Aim

This study aimed to evaluate the effect of trimetazidine (TMZ) in addition to standard treatment on exercise tolerance in patients with ischemic heart disease (IHD).

Methods

Studies were identified via a systematic search of PubMed, Embase, Cochrane Library, and the Chinese CNKI databases from January 1978 to January 2015. Data extraction, synthesis, and statistical analysis were performed by standard meta-analysis methods. Random or fixed effects models were used to estimate pooled mean differences in total exercise duration (TED), peak oxygen uptake (pVO2), metabolic equivalent system (METS), and 6-minute walking test (6-MWT).

Results

In all, 16 randomized controlled trials (RCTs) consisting of 2,004 participants were included. Pooled results showed that TMZ treatment significantly improved TED (WMD: 37.35, 95 % CI: 25.58–49.13, p < 0.00001), pVO2 (WMD: 2.41, 95 % CI: 1.76–3.06, p < 0.00001), METS (WMD: 1.33, 95 % CI: 0.38–2.28, p = 0.006), and 6-WMT (WMD: 62.46, 95 % CI: 35.86–89.05, p < 0.001) in all patients with IHD. Subgroup analysis showed that TMZ significantly increased TED in nondiabetic participants (WMD 34.77, 95 % CI: 22.28–47.25, p < 0.001), but not in diabetic participants (WMD: 40.36, 95 % CI: − 18.76–99.48, p = 0.18). And, subgroup analysis of TED by intervention duration suggested that there is no statistically difference between the 3-month and 6-month periods (WMD: 35.47, 95 %CI: 18.35–52.60, p < 0.0001 and WMD: 49.94, 95 %CI: 44.69–55.19, p < 0.00001). In addition, TMZ improved TED (WMD: 50.01, 95 % CI: 44.77–55.25 and WMD: 24.20, 95 % CI: 12.72–35.68) in IHD patients with or without heart failure (HF), respectively.

Conclusion

Addition of TMZ to standard treatment significantly improved exercise tolerance in patients with IHD, and IHD patients with HF may experience even more benefits. However, there is insufficient evidence to show that TMZ has beneficial effects in participants with diabetes.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war es, die Wirkung von Trimetazidin (TMZ) zusätzlich zu der Standardtherapie auf die Belastungstoleranz bei Patienten mit ischämischer Herzerkrankung („ischemic heart disease“, IHD) zu untersuchen.

Methoden

Studien wurden über eine systematische Suche in den Datenbanken PubMed, Embase, Cochrane Library und in der chinesischen CNKI (China National Knowledge Infrastructure) von Januar 1978 bis Januar 2015 gesucht. Die Datenerfassung, -synthese und statistische Analyse erfolgten mit Standardmethoden der Metaanalyse. Random- oder Fixed-Effects-Modelle wurden eingesetzt, um die gepoolten mittleren Differenzen bei der Gesamtbelastungsdauer („total exercise duration“, TED), der Spitzensauerstoffaufnahme („peak oxygen uptake“, pVO2), dem metabolischen Äquivalentsystem („metabolic equivalent system“, METS) und dem 6-min-Gehtest („6-minute walking test“, 6-MWT) abzuschätzen.

Ergebnisse

Es wurden 16 randomisierte kontrollierte Studien (RCT) mit 2004 Teilnehmern in die Auswertung eingeschlossen. Die gepoolten Ergebnisse zeigten, dass die TMU-Behandlung zu einer signifikanten Verbesserung der TED (gewichtete mittlere Differenz, WMD: 37,35; 95 %-Konfidenzintervall, 95%-KI: 25,58–49,13; p < 0,00001), der pVO2 (WMD: 2,41; 95 %-KI: 1,76–3,06; p < 0,00001), des METS (WMD: 1,33; 95 %-KI: 0,38–2,28; p = 0,006) und des 6-WMT (WMD: 62,46; 95 %-KI: 35,86–89,05; p < 0,001) bei allen Patienten mit IHD führte.

Die Subgruppenanalyse ergab, dass TMZ die TED bei Teilnehmern ohne Diabetes mellitus signifikant erhöhte (WMD 34,77; 95 %-KI: 22,28–47,25; p < 0,001), nicht aber bei Teilnehmern mit Diabetes (WMD: 40,36; 95 %-KI: − 18,76–99,48; p = 0,18). Und aus der Subgruppenanalyse der TED nach Interventionsdauer ergaben sich Hinweise darauf, dass statistisch kein Unterschied zwischen der 3-monatigen und der 6-monatigen Dauer bestehe (WMD: 35,47; 95 %-KI: 18,35–52,60; p < 0,0001 bzw. WMD: 49,94; 95 %-KI: 44,69–55,19; p < 0,00001). Außerdem zeigte sich eine Verbesserung der TED unter TMZ (WMD: 50,01; 95 %-KI: 44,77–55,25 bzw. WMD: 24,20; 95 %-KI: 12,72–35,68) bei IHD-Patienten mit bzw. ohne Herzinsuffizienz.

Schlussfolgerung

Die zusätzliche Gabe von TMZ zur Standardbehandlung verbesserte die Belastungstoleranz signifikant bei Patienten mit ischämischer Herzerkrankung. IHD-Patienten mit Herzinsuffizienz haben möglicherweise noch einen größeren Nutzen. Es gibt jedoch keine ausreichende Evidenz dafür, dass TMZ einen Nutzeffekt bei Teilnehmern mit Diabetes mellitus habe.

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Authors and Affiliations

  1. Department of Cardiology, the Third Affiliated Hospital, Sun Yat-sen University, Tian-he Road, 510630, Guangzhou, China

    Y. Zhao, L. Peng, Y. Luo, S. Li, Z. Zheng, R. Dong, J. Zhu & J. Liu

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  1. Y. Zhao
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Correspondence to J. Liu.

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Y. Zhao, L. Peng, Y. Luo, S. Li, Z. Zheng, R. Dong, J. Zhu, and J. Liu state that there are no conflicts of interest.

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Zhao, Y., Peng, L., Luo, Y. et al. Trimetazidine improves exercise tolerance in patients with ischemic heart disease. Herz 41, 514–522 (2016). https://doi.org/10.1007/s00059-015-4392-2

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