Clinical outcomes in diabetic and non-diabetic patients with drug-eluting stents: results from the first phase of the prospective multicenter German DES.DE registry.

BACKGROUND: Patients with diabetes mellitus (DM) undergoing coronary revascularization are at increased risk for adverse outcomes. Without sufficiently powered data from diabetic subgroup analyses and in absence of randomized controlled trials in diabetic patients with primary clinical outcomes controversy is ongoing over safety and efficacy of drug-eluting stents (DES) in diabetic patients. METHODS AND RESULTS: Between October 2005 and October 2006, 1,659 diabetic and 3,559 non-diabetic patients treated with DES (Paclitaxel or Sirolimus-eluting stents) were enrolled at 98 Drug-Eluting-Stent.DEutschland (DES.DE) sites. Major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of death, myocardial infarction, and stroke, as well as target vessel revascularization (TVR) were defined as primary endpoints. The baseline clinical and descriptive morphology of coronary artery disease revealed more severe findings in diabetic patients. At 1-year follow-up, diabetic patients treated with DES had significantly higher rates for overall death (5.6 vs. 3.4%; p < 0.01), myocardial infarction (4.8 vs. 3.4%; p = 0.05), stroke (1.7 vs. 0.9%; p < 0.05), MACCE (10.9 vs. 7.1%; p < 0.001), and overall stent thrombosis (4.9 vs. 3.3%; p < 0.01) with slightly elevated rates for TVR (12.0 vs. 10.4%; p = 0.17); data which remained after risk-adjustment. CONCLUSION: Data collected in DES.DE revealed that despite the use of DES the risk of myocardial infarction, death, and thrombotic events remains higher in diabetic patients.

Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: final 1-year results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial.

BACKGROUND: Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown. METHODS AND RESULTS: Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85+/-30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, beta-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNC(CD34+)), with a 20-fold increase (from 3+/-2 at baseline to 66+/-54 MNC(CD34+)/microL on day 6; P<0.001); there was no evidence of leukocytoclastic effects, accelerated restenosis rate, or any late adverse events. Within 4 months, G-CSF-induced MNC(CD34+) mobilization led to enhanced resting wall thickening in the infarct zone of 1.16+/-0.29 mm (P<0.05 versus control), which was sustained at 1.20+/-0.28 after 12 months (P<0.001 versus control). Similarly, left ventricular ejection fraction improved from 48+/-4% at baseline to 54+/-8% at 4 months (P<0.005 versus control) and 56+/-9% at 12 months (P<0.003 versus control and paralleled by sustained improvement of wall-motion score index from 1.70+/-0.22 to 1.42+/-0.26 and 1.33+/-0.21 at 4 and 12 months, respectively), after G-CSF (P<0.05 versus baseline and P<0.03 versus controls). Accordingly, left ventricular end-diastolic diameter showed no remodeling and stable left ventricular dimensions after G-CSF stimulation, whereas left ventricular end-diastolic diameter in controls revealed enlargement from 55+/-4 mm at baseline to 58+/-4 mm (P<0.05 versus baseline) at 12 months after infarction and no improvement in diastolic function. CONCLUSIONS: Mobilization of MNC(CD34+) by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling 1 year after acute myocardial infarction.