Paul Barragan

BACKGROUND: The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization. Because sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle cells, we compared a sirolimus-eluting stent with a standard uncoated stent in patients with angina pectoris. METHODS: We performed a randomized, double-blind trial to compare the two types of stents for revascularization of single, primary lesions in native coronary arteries. The trial included 238 patients at 19 medical centers. The primary end point was in-stent late luminal loss (the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months). Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis (luminal narrowing of 50 percent or more). We also analyzed a composite clinical end point consisting of death, myocardial infarction, and percutaneous or surgical revascularization at 1, 6, and 12 months. RESULTS: At six months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the sirolimus-stent group, as compared with 26.6 percent of those in the standard-stent group, had restenosis of 50 percent or more of the luminal diameter (P<0.001). There were no episodes of stent thrombosis. During a follow-up period of up to one year, the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001). The difference was due entirely to a higher rate of revascularization of the target vessel in the standard-stent group. CONCLUSIONS: As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events.

BACKGROUND: When administered in conjunction with primary coronary stenting for the treatment of acute myocardial infarction, a platelet glycoprotein IIb/IIIa inhibitor may provide additional clinical benefit, but data on this combination therapy are limited. METHODS: We randomly assigned 300 patients with acute myocardial infarction in a double-blind fashion either to abciximab plus stenting (149 patients) or placebo plus stenting (151 patients) before they underwent coronary angiography. Clinical outcomes were evaluated 30 days and 6 months after the procedure. The angiographic patency of the infarct-related vessel and the left ventricular ejection fraction were evaluated at 24 hours and 6 months. RESULTS: At 30 days, the primary end point--a composite of death, reinfarction, or urgent revascularization of the target vessel--had occurred in 6.0 percent of the patients in the abciximab group, as compared with 14.6 percent of those in the placebo group (P=0.01); at 6 months, the corresponding figures were 7.4 percent and 15.9 percent (P=0.02). The better clinical outcomes in the abciximab group were related to the greater frequency of grade 3 coronary flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) in this group than in the placebo group before the procedure (16.8 percent vs. 5.4 percent, P=0.01), immediately afterward (95.1 percent vs. 86.7 percent, P=0.04), and six months afterward (94.3 percent vs. 82.8 percent, P=0.04). One major bleeding event occurred in the abciximab group (0.7 percent); none occurred in the placebo group. CONCLUSIONS: As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

We carried out a prospective evaluation of a new vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay in order to detect patients with high-risk coronary subacute stent thrombosis (SAT) despite thienopyridine regimen. Twenty healthy donors (group 1) without any medication were compared to 16 stented patients (group 2) treated by ticlopidin or clopidogrel initiated 2 days before stenting and aspirin (250 mg/day). No difference in platelet reactivity was noted between group 1 and group 2 treated only with aspirin (72.00% +/- 4.17% vs. 69.73% +/- 5.62%, respectively; P = NS). Significant differences were found between patients of group 2 treated with aspirin alone (69.73% +/- 5.62%), after 2.0 days (60.14% +/- 9.60%; P < 0.05), and after 4.8 +/- 1.3 days (48.37% +/- 11.19%; P < 0.05) with thienopyridine-aspirin. Among 1,684 consecutive stented patients, 16 patients who presented an SAT (group 3) were compared with 30 other stented patients free of SAT (group 4). We found a significant difference between group 3 (63.28% +/- 9.56%) and group 4 (39.80% +/- 10.9%; P < 0.0001). VASP phosphorylation analysis may be useful for the detection of coronary SAT.