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SITAGRAMI: Progenitor cell therapy fails to show CV benefits
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The combination of sitagliptin and granulocyte colony–stimulating factor did not improve myocardial function in patients after acute MI, according to results of the SITAGRAMI trial published in the International Journal of Cardiology.
In animal models, progenitor cell therapy using granulocyte colony–stimulating factor (G-CSF) and a dipeptidyl-peptidase IV inhibitor has increased the number of bone marrow-derived circulating cardioprotective progenitor cells being recruited to the injured myocardium, resulting in improved ejection fraction and survival after acute MI. The SITAGRAMI trial is the first study to investigate whether the same positive effects could be seen in humans, according to the researchers.
In this multicenter, prospective, placebo-controlled, parallel-group, double blind, phase 3 efficacy and safety trial, 174 patients were randomly assigned to G-CSF combined with sitagliptin (Januvia, Merck) or placebo after successful revascularization in acute MI. More than 88% of patients had STEMI and 11.5% had non-STEMI.
Patients assigned the intervention were given 10 µg/kg/day of lenograstim divided into two doses administered subcutaneously over 5 days and 100 mg sitagliptin given orally each day for 28 days.
The primary efficacy endpoint was a combination of global left and right ventricular ejection fraction changes from baseline to 6 months of follow-up. Secondary endpoints included changes in global and regional myocardial function, myocardial perfusion and infarct volume. Major adverse cardiac events also were investigated.
According to study results, left ventricular ejection fraction increased from 52.2% to 56.9% in the placebo group and from 51.7% to 56.2% in the treatment group; however, the intent-to-treat analysis showed no evidence that the mean change in LVEF was larger in the treatment group compared with the placebo group (P = .471). Right ventricular ejection fraction changed very little from baseline to 6 months in the placebo (55% to 55.3%) or the treatment group (56.7% to 56.8%). The researchers also observed no difference in the presence and transmural extent of MI (30.9% vs. 26.3%; P = .772) or myocardial perfusion (0.82% vs. 0.82%; P = .972).
Overall, 39 major adverse cardiac events occurred (placebo: 22 [one patient had two major adverse cardiac events]; intervention: 17). In the intent-to-treat population, the researchers reported no change in risk for MACE for up to 12 months (HR = 0.785; 95% CI, 0.414-1.488; P = .458).
According to the researchers, there are possible explanations for these neutral results including a different dosage amount between mice and men, possibly resulting in insufficient effect on the heart; the mice did not undergo revascularization, nor did they receive standard HF therapy such as ACE inhibitors or beta-blockers; and the timing of the study drug administration may have been an issue.
The researchers concluded, however, that “hopeful tools for cardiac regeneration may lie in reprogramming, purification and culture of cardiac progenitor cells in the future.” – by Tracey Romero
Disclosure: Two of the researchers report receiving honorarium from Merck.
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