Safety and efficacy of consecutive cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: the G-CSF in angina patients with IHD to stimulate neovascularization (GAIN I) trial.

BACKGROUND

Preclinical studies suggest granulocyte-colony stimulating factor (G-CSF) holds promise for treating ischemic heart disease; however; its clinical safety and efficacy in this setting remain unclear. We elected to evaluate the safety and efficacy of G-CSF administration in patients with refractory "no-option" ischemic heart disease.

METHODS

Twenty patients (18 males, 2 females, mean age 62.4 years) were enrolled and underwent baseline cardiac ischemia assessment (CA) (angina questionnaire, exercise stress test [EST], technetium Tc 99m sestamibi and dobutamine-stress echocardiographic imaging). Patients then received open-label G-CSF commencing at 10 microg/kg SC for 5 days, with an EST on days 4 and 6 (to facilitate myocardial cytokine generation and stem cell trafficking). After 3 months, CA and the same regimen of G-CSF+ESTs were repeated but, in addition, leukapheresis and a randomized double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final CA occurred 3 months thereafter.

RESULTS

There were no deaths, but only 16 patients were permitted to complete the study. Eight events fulfilled prespecified "adverse event" criteria, including 4 troponin I-positive events and 2 episodes of thrombocytopenia. Also, frequent minor troponin I-positive events (troponin I<0.9 microg/L) were observed, which did not meet adverse event criteria. The administration of consecutive cycles of G-CSF resulted in stepwise improvements in anginal frequency, EST performance, and Duke treadmill scores (all P<.005). However, from baseline to final follow-up, technetium Tc 99m sestamibi and dobutamine-stress echocardiographic results were unchanged.

CONCLUSIONS

Granulocyte-colony stimulating factor administration was associated with improvement in a range of subjective outcomes. However, adverse events were common, and objective measures of cardiac perfusion/ischemia were unchanged.