A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial
Selected in European Heart Journal by G.G. Toth
Choudry F, Hamshere S, Saunders N, Veerapen J, Bavnbek K, Knight C, Pellerin D, Locca D, Westwood M, Rakhit R, Crake T, Kastrup J, Parmar M, Agrawal S, Jones D, Martin J, Mathur A
Eur Heart J. 2016 Jan 14;37(3):256-63
LinkRead the abstract
Revascularization therapies have resulted in massive improvements of survival after myocardial infarction. Still, post-infarct ischemic heart failure is a marked issue with limited therapeutic approaches. Although not decisive, some data in the literature suggest that intracoronary administration of autologous bone marrow-derived cells (BMC) might have beneficial effect on left ventricular function in patients after myocardial infarction. The proper timing of the therapy is supposed to be crucial, but it is still undefined.
REGENERATE-AMI was a multi-centric double-blinded, randomized, placebo-controlled trial. The aim of the study was to determine if ‘very early’ delivery of autologous BMC following anterior AMI is safe, feasible and efficacious in the improvement of left ventricular function. The primary endpoint was the absolute change in left ventricular ejection fraction at 1 year compared with baseline.
- The study enrolled patients (n=100) with diagnosis of acute anterior myocardial infarction, successfully treated with primary PCI within 24 hours after the onset of the symptoms. The median time from primary PCI to intracoronary infusion was similarly very short in both groups: 532 min in the BMC group (range 403–1312) and 583 min in the placebo group (range 458–1276).
- The left ventricular ejection fraction increased significantly in both groups between baseline and 1-year follow-up: in BMC group by 5.1% from 47.5 ± 9.2% to 52.6 ± 10.5%, respectively (p < 0.01) and in placebo group by 2.8% from 49.2 ± 9.6% to 52.0 ± 9.1%, respectively (p < 0.01). The difference between the two groups is statistically not significant.
- The infarct size at day 3 was smaller in the BMC group than in the placebo group (−5.4%; 95% CI: −9.4 to −1.4; p < 0.01). The myocardial salvage index (calculated as the ratio of infarct size and area at risk) at day 3 was greater in the BMC group than in the placebo group (0.1%; 95% CI: 0.0–0.2; p = 0.05). There was a greater reduction in infarct size in the placebo group compared with the BMC group over time (4.1%; 95% CI: 0.3–7.9; p = 0.03)
- There were no within-group or between-group differences observed in left ventricular end-systolic and end-diastolic volumes or cardiac output at either 3 or 12 months.
- Overall, there was similar occurrence of MACE in the two groups. No cases of distal coronary artery occlusion occurred during intracoronary infusion. There were no significant differences in safety events between the groups.
The application of stem cell therapy to facilitate ‘healing’ of infarcted myocardium is still one of the big promises of cardiology. However the definite judgment about its true clinical potential is still missing, and it will remain undefined, as long as the ‘best clinical practice’ of the method is unclear.
This trial validated successfully the applicability of ‘very early’ autologous BMC injection, as no safety issues have been detected. But no significant difference has been shown compared to placebo in any of the clinical or imaging endpoints. The latter might be the consequence of the underpowered design. Therefore, only larger trials can validly evaluate the true clinical value of stem cell therapy.