The intracoronary (IC) infusion of bone marrow mono-nuclear cells after an STEMI improved cardiac function, including left ventricular ejection fraction (LVEF), infarct size, and end-systolic volume, and major adverse cardiac events (MACEs) [Huikuri HV et al. Eur Heart J. 2008; Martin-Rendon E et al. Eur Heart J. 2008; Schachinger V et al. N Engl J Med. 2006]. A phase 1 study demonstrated the feasibility and safety of IC infusion of autologous CD34⁺ cells after an acute STEMI, and a dose-dependent improvement in perfusion [Quyyumi AA et al. Am Heart J. 2011].

The phase 1 study suggested a threshold dose of 10 million CD34⁺ cells for bioactivity, stated Arshed A. Quyyumi, MD, Emory University School of Medicine, Atlanta, Georgia, USA, and provided the basis for the phase 2 NBS10 (Also Known as AMR-001) Versus Placebo Post ST Segment Elevation Myocardial Infarction trial [PreSERVE-AMI; NCT01495364].

The double-blind PreSERVE-AMI trial randomized patients to IC autologous CD34⁺ cells (NBS10) or matching placebo at days 6 and 11 after stent placement. The patients had an acute STEMI and were stented within 3 days of chest pain onset; had reduced LVEF (≤ 45% to 48%) and wall motion abnormality; and were NYHA class I, II, or III. An infusion was given to 78 of the 100 patients in the NBS10 arm and 83 of the 95 patients in the placebo arm.

The patients had a mean age of 57 years, and most were men (about 80%). The mean LVEF was 34%, and the mean left ventricular end diastolic and systolic volume indices were 92 (placebo) to 98 (treated) and 58 (placebo) to 61 (treated), respectively. The time from symptom onset to stent placement was significantly longer in the NBS10 vs placebo arm (mean 931 vs 569 minutes; P = .041). Serious adverse events (SAEs) were low and similar in both arms at bone marrow harvest and infusion.

There was a similar rate of the primary safety outcome of AEs (63%; P = .89) and SAEs (36%; P = .97) at the median 12-month follow-up. A dose-dependent reduction in the proportion of SAEs was seen with the higher doses of NBS10 vs placebo.

The primary outcome of MACEs, comprising cardiac death, recurrent myocardial infarction (MI), heart failure (HF) hospitalization, or coronary revascularization, was similar at 6 months at 19.2% and 16.9% of the NBS10 and placebo arms (P = .66). Mortality was significantly lower with NBS10 (0 vs 3 with placebo; P = .04). A nonsignificant dose-dependent reduction in MACEs was observed with the higher NBS10 doses (10% for > 14 million cells; 7% for > 20 million cells; 14% for placebo; 17% for < 14 million cells).

The primary outcome of mean change in myocardial perfusion at 6 months was −142.7 with NBS10 and −149.6 with placebo (P = NS), measured by the single-photon emission computed tomography resting total severity score. A nonsignificant reduction was found for the secondary outcome of mean change in LVEF at 6 months (4.1% with NBS10 vs 4.9% with placebo). A dose-dependent improvement in LVEF was found with the higher doses of NBS10 vs placebo. A relation between greater improvement and the higher NBS10 doses was suggested by a multiple regression model adjusted for time from pain onset to stenting (P = .045).

PreSERVE-AMI showed IC NBS10 was well tolerated and safe in patients with an acute STEMI. Although there were no significant differences in the primary end point of cardiac death, recurrent MI, HF hospitalization, or coronary revascularization, there was evidence that higher doses of stem cells may improve LVEF. These findings provide some evidence that this therapy may be beneficial and should be further tested to determine if stem cells can improve outcomes in patients with acute MI.