Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8).

OBJECTIVE

To assess the effect of intracoronary infusion of mesenchymal stem cells on the development of post-myocardial infarction heart failure.

DESIGN

Phase 3 randomised clinical trial.

SETTING

Three tertiary hospitals in Shiraz, Iran.

PARTICIPANTS

420 patients with a first ST segment elevation acute myocardial infarction and left ventricular ejection fraction <40% were enrolled and randomised in a 1:2 ratio to receive intervention or standard care.

INTERVENTION: Intracoronary infusion of allogenic Wharton's jelly derived mesenchymal stem cells within 3-7 days of acute myocardial infarction in addition to standard care.

MAIN OUTCOME MEASURES: The primary endpoint was incidence of heart failure. Secondary endpoints included readmission to hospital for heart failure, all cause mortality, cardiovascular mortality, and readmission to hospital for myocardial infarction. Changes in left ventricular ejection fraction within six months post-myocardial infarction were compared between groups.

RESULTS

A total of 396 patients (136 in the intervention group and 260 in the control group) were included in the final analysis, with a median follow-up of 33.2 months. Intracoronary infusion of mesenchymal stem cells had a preventive effect for incidence of heart failure (2.77 v 6.48 per 100 person years; hazard ratio 0.43, 95% confidence interval 0.21 to 0.89; P=0.024), readmission to hospital for heart failure (0.92 v 4.20 per 100 person years; 0.22, 0.06 to 0.74; P=0.015), and a composite endpoint of cardiovascular mortality and readmission for myocardial infarction or heart failure (2.80 v 7.16 per 100 person years; 0.39, 0.19 to 0.82; P=0.012). The intervention did not have a statistically significant effect on readmission to hospital for myocardial infarction (1.23 v 3.06 per 100 person years; hazard ratio 0.40, 0.14 to 1.19; P=0.10), all cause mortality (1.81 v 1.66 per 100 person years; 1.10, 0.40 to 3.02; P=0.86), or cardiovascular mortality (0.91 v 1.33 per 100 person years; 0.68, 0.18 to 2.57; P=0.57). Left ventricular ejection fraction in the intervention group showed a significantly greater improvement from baseline at six months compared with the control group (β=5.88, 95% confidence interval 4.00 to 7.76; P<0.001).

CONCLUSIONS

Intracoronary infusion of Wharton's jelly derived mesenchymal stem cells significantly reduced the risk of incidence of heart failure, readmission to hospital for heart failure, and the composite endpoint of cardiovascular mortality and readmission to hospital for heart failure or myocardial infarction in patients after an acute myocardial infarction, suggesting that this technique may serve as a valuable adjunctive procedure after myocardial infarction to prevent the development of heart failure and reduce the risk of future adverse events.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05043610.