Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study.

BACKGROUND: Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promising results in experimental models and phase I/IIA clinical trials. The GPAD-3 trial will study the effect of two successive administrations of GM-CSF at 3-month interval for improving claudication among patients with lower extremity PAD. METHODS: We plan to recruit 176 patients in this ongoing randomized, double-blind, placebo-controlled Phase IIB trial. After screening for inclusion and exclusion criteria, eligible subjects undergo a 4-week screening phase where they perform subcutaneous placebo injections thrice weekly and walk at least three times a day until they develop claudication. After the screening phase, eligible subjects undergo baseline testing and are randomized 2:1 to receive 500 µg/day of GM-CSF subcutaneously thrice weekly for three weeks or placebo injections. After 3 months, follow-up endpoint testing is performed and subjects in the GM-CSF group receive the second administration of the drug for three weeks while subjects in placebo group receive matching placebo injections. All participants undergo endpoint testing at six-month and nine-month follow-up. The primary endpoint is change in 6-min walk distance between baseline and 6-month follow-up. CONCLUSION: GPAD-3 explores a novel approach to address the need for alternative therapies that can alleviate symptoms among patients with lower extremity PAD. If successful, this study will pave the way for a pivotal Phase III trial.

Percutaneous Coronary Intervention in Native Coronary Arteries Versus Bypass Grafts in Patients With Prior Coronary Artery Bypass Graft Surgery: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

OBJECTIVES: The aim of this study was to examine the frequency, associations, and outcomes of native coronary artery versus bypass graft percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafting (CABG) in the Veterans Affairs (VA) integrated health care system. BACKGROUND: Patients with prior CABG surgery often undergo PCI, but the association between PCI target vessel and short- and long-term outcomes has received limited study. METHODS: A national cohort of 11,118 veterans with prior CABG who underwent PCI between October 2005 and September 2013 at 67 VA hospitals was examined, and the outcomes of patients who underwent native coronary versus bypass graft PCI were compared. Logistic regression with generalized estimating equations was used to adjust for correlation between patients within hospitals. Cox regressions were modeled for each outcome to determine the variables with significant hazard ratios (HRs). RESULTS: During the study period, patients with prior CABG represented 18.5% of all patients undergoing PCI (11,118 of 60,171). The PCI target vessel was a native coronary artery in 73.4% and a bypass graft in 26.6%: 25.0% in a saphenous vein graft and 1.5% in an arterial graft. Compared with patients undergoing native coronary artery PCI, those undergoing bypass graft PCI had higher risk characteristics and more procedure-related complications. During a median follow-up period of 3.11 years, bypass graft PCI was associated with significantly higher mortality (adjusted HR: 1.30; 95% confidence interval: 1.18 to 1.42), myocardial infarction (adjusted HR: 1.61; 95% confidence interval: 1.43 to 1.82), and repeat revascularization (adjusted HR: 1.60; 95% confidence interval: 1.50 to 1.71). CONCLUSIONS: In a national cohort of veterans, almost three-quarters of PCIs performed in patients with prior CABG involved native coronary artery lesions. Compared with native coronary PCI, bypass graft PCI was significantly associated with higher incidence of short- and long-term major adverse events, including more than double the rate of in-hospital mortality.