A prospective, nonrandomized, open-labeled pilot study investigating the use of magnesium in patients undergoing nonacute percutaneous coronary intervention with stent implantation.

BACKGROUND: Magnesium has recently been shown to inhibit acute stent thrombosis in animal models. This study tested the feasibility of magnesium administration in patients undergoing nonacute percutaneous coronary intervention with stent implantation. METHODS: Twenty-one patients undergoing nonemergent percutaneous coronary intervention were enrolled and received intravenous magnesium sulfate (2-g bolus over 20 minutes prepercutaneous coronary intervention, followed by 14 g over 12 hours infusion). ENDPOINTS: safety outcomes--hypotension, bradycardia, bleeding complications and heart block within first 24 hours; angiographic outcomes--acute thrombotic occlusion and need for platelet glycoprotein IIb/IIIa inhibitor bailout; and clinical outcomes--death, myocardial infarction, recurrent ischemia, and need for urgent revascularization at 48 hours and 30 days. RESULTS: No significant effects on heart rate or blood pressure, major bleeding complication, or new electrocardiographic changes were observed. Angiographic thrombus was visualized in two cases, and coronary artery dissection in one case poststent deployment. None of these cases required the use of glycoprotein inhibitors for bailout. Death, myocardial infarction, recurrent ischemia, and need for urgent revascularization were not observed. The serum magnesium level increased from 2.1 +/- 0.3 mg/dL at baseline to 3.5 +/- 0.8 mg/dL at the end of the infusion (P <.0001). Platelet activation was significantly inhibited at the end of the magnesium sulfate infusion. CONCLUSION: Intravenous magnesium sulfate has been demonstrated as a feasible and safe agent in patients undergoing nonacute percutaneous coronary intervention with stent implantation. A randomized clinical trial comparing magnesium with glycoprotein inhibitors during percutaneous coronary intervention is warranted.

Intramural delivery of recombinant apolipoprotein A-IMilano/phospholipid complex (ETC-216) inhibits in-stent stenosis in porcine coronary arteries.

BACKGROUND: We have previously demonstrated vasculoprotective effects after repeated intravenous administration of recombinant apolipoprotein A-IMilano (apoA-Im)/phospholipid complex. In this study, we sought to determine the effects of local recombinant apoA-Im/1-palmitoyl,2-oleoyl phosphatidylcholine complex (ETC-216) delivered intramurally via the Infiltrator catheter on luminal narrowing in a porcine coronary artery stent overstretch injury model. METHODS AND RESULTS: In twelve domestic swine ( approximately 25 kg), two arteries each were infiltrated with 0.4 mL ETC-216 (14 mg/mL) or vehicle control immediately before deployment of GFX stents (stent:artery ratio=1.3:1). Animals were euthanized at day 28, and evaluation by QCA revealed a significant improvement in mean lumen loss index with ETC-216 treatment (21+/-22% versus 43+/-13% lumen loss; P=0.01). Histomorphometric analysis showed that ETC-216 treatment significantly reduced the intimal area (6.7+/-1.5 versus 5.2+/-1.4 mm2, -22%; P=0.02) and the stenosis index (0.76+/-0.15 versus 0.59+/-0.15; P=0.01), and increased the lumen area (2.1+/-1.4 versus 3.7+/-1.8 mm2, +76%; P=0.02). Regression analysis showed significant differences in lumen area (P=0.004), neointimal area (P=0.003), stenosis index (P=0.001), and neointimal thickness (P=0.003) adjusted for injury score in favor of ETC-216. CONCLUSIONS: A single intramural administration of ETC-216 significantly inhibited injury-induced luminal narrowing in the porcine stent overstretch model through reduction of intimal hyperplasia. These data show that local intracoronary delivery of ETC-216 may be useful to prevent restenosis after coronary stenting.