Objective To test whether intensive atorvastatin (ATV) increases the efficacy of transplantation with autologous bone marrow mononuclear cells (MNCs) in patients suffering from anterior ST-elevated myocardial infarction (STEMI).
Methods This clinical trial was under a 2×2 factorial design, enrolling 100 STEMI patients, randomly into four groups of regular (RA) or intensive ATV (IA) with MNCs or placebo. The primary endpoint was the change of left ventricular ejection fraction (LVEF) at 1-year follow-up from baseline, primarily assessed by MRI. The secondary endpoints included other parameters of cardiac function, remodelling and regeneration determined by MRI, echocardiography, positron emission tomography (PET) and biomarkers.
Results All the STEMI patients with transplantation of MNCs showed significantly increased LVEF change values than those with placebo (p=0.01) with only in the IA+MNCs patients group demonstrating significantly elevation of LVEF than in the IA+placebo group (+12.6% (95%CI 10.4 to 19.3) vs +5.0% (95%CI 4.0 to 10.0), p=0.001), pointing to a better synergy between ATV and MNCs (p=0.019). PET analysis revealed significantly increased viable areas of myocardium (p=0.015), while the scar sizes (p=0.026) and blood aminoterminal pro-B-type natriuretic peptide (p<0.034) reduced. All these above benefits of MNCs were also attributed to IA+MNCs instead of RA+MNCs group of patients with STEMI.
Conclusions Intensive ATV treatment augments the therapeutic efficacy of MNCs in patients with anterior STEMI at the convalescent stage. The treatment with the protocol of intensive ATV and MNC combination offers a clinically essential approach for myocardial infarction.
Trial registration number NCT00979758.
- acute coronary syndrome
- myocardial perfusion
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Y-JY and H-YQ contributed equally.
Contributors The coauthors including Y-JY, Y-JG, H-YQ and R-LG contributed to the planning, the coauthors including LS, NL, HW, X-QT, JH, P-SH, JX, RS, M-JL, S-HZ, W-CW and JQ contributed to the conduct and the coauthors including YW, JZ, J-YX and Y-YX contributed to the reporting of the work in the article. Among the above coauthors, professors Y-JY and H-YQ are responsible for the overall contents as guarantors. We did not include any figure or table from another publication.
Funding Y-JY was supported by grants from CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-12 M-1-009), National Basic Research Program (973 Program) in China (no: 2012CB518602, Ministry of Science and Technology), National High Technology Research and Development Program (863 Program) in China (no: 2013AA020101, Ministry of Science and Technology), National Natural Science Foundation of China (no: 81170129), Research Fund of Capital Medical Development (no: 2007–2018) and China Health and Medical Development Foundation (2008-zhfj2, 2011-zhfj1, 2015-zhfj2). H-YQ was supported by grants from the Clinical and Translational Medicine Research Foundation of Chinese Academy of Medical Sciences (2019XK320061), and National Natural Science Foundation of China (nos: 81000091, 81670337).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The institutional review boards of Fuwai Cardiovascular Hospital of the Chinese Academy of Medical Sciences reviewed and approved the study protocol.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. The related data can be requested from the co-author Professor H-YQ via email at email@example.com.
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