The effect of pegylated granulocyte colony-stimulating factor on collateral function and myocardial ischaemia in chronic coronary artery disease: A randomized controlled trial

Objective To test the effect of long-term pegfilgrastim on collateral function and myocardial ischaemia in patients with chronic stable coronary artery disease (CAD). Methods This was a prospective clinical trial with randomized 2:1 allocation to pegfilgrastim or placebo for 6 months. The primary study endpoint was collateral flow index (CFI) as obtained during a 1-minute ostial coronary artery balloon occlusion. CFI is the ratio of mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure (mm Hg/mm Hg). Secondary endpoints were signs of myocardial ischaemia determined during the same coronary occlusion, that is quantitative intracoronary (i.c.) ECG ST-segment shift (mV) and the occurrence of angina pectoris. Endpoints were obtained at baseline before and at follow-up after three subcutaneous study drug injections. Results Collateral flow index in the pegfilgrastim group changed from 0.096 +/- 0.076 at baseline to 0.126 +/- 0.070 at follow-up (P = 0.0039), while in the placebo group CFI changed from 0.157 +/- 0.146 to 0.122 +/- 0.043, respectively (P = 0.29); the CFI increment at follow-up was +0.030 +/- 0.075 in the pegfilgrastim group and -0.034 +/- 0.148 in the placebo group (P = 0.0172). In the pegfilgrastim group, i.c. ECG ST-segment shift changed from +1.23 +/- 1.01 mV at baseline to +0.93 +/- 0.97 mV at follow-up (P = 0.0049), and in the placebo group, it changed from +0.98 +/- 1.02 mV to +1.43 +/- 1.09 mV, respectively (P = 0.05). At follow-up, the fraction of patients free from angina pectoris during coronary occlusion had increased in the pegfilgrastim but not in the placebo group. Conclusion Pegfilgrastim given over the course of 6 months improves collateral function in chronic stable CAD, which is reflected by reduced myocardial ischaemia during a controlled coronary occlusion.