Popma, Jeffrey J.

Background— Stroke occurs more commonly after carotid artery stenting than after carotid endarterectomy. Details regarding stroke type, severity, and characteristics have not been reported previously. We describe the strokes that have occurred in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Methods and Results— CREST is a randomized, open-allocation, controlled trial with blinded end-point adjudication. Stroke was a component of the primary composite outcome. Patients who received their assigned treatment within 30 days of randomization were included. Stroke was adjudicated by a panel of board-certified vascular neurologists with secondary central review of clinically obtained brain images. Stroke type, laterality, timing, and outcome were reported. A periprocedural stroke occurred among 81 of the 2502 patients randomized and among 69 of the 2272 in the present analysis. Strokes were predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4-year mortality after stroke was 21.1% compared with 11.6% for those without stroke. The adjusted risk of death at 4 years was higher after periprocedural stroke (hazard ratio, 2.78; 95% confidence interval, 1.63–4.76). Conclusions— Stroke, particularly severe stroke, was uncommon after carotid intervention in CREST, but stroke was associated with significant morbidity and was independently associated with a nearly 3-fold increased future mortality. The delayed timing of major and hemorrhagic stroke after revascularization suggests that these strokes may be preventable. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00004732.

Background— Sirolimus-eluting stents (SESs) reduce angiographic restenosis in patients with focal, native coronary artery stenoses. This study evaluated the usefulness of SESs in complex native-vessel lesions at high risk for restenosis. Methods and Results— Angiographic follow-up at 240 days was obtained in 701 patients with long (15- to 25-mm) lesions in small-diameter (2.5- to 3.5-mm) native vessels who were randomly assigned to treatment with SESs or bare-metal stents (BMSs) in the SIRIUS trial. Quantitative angiographic measurements of minimal lumen diameter and percent diameter stenosis were obtained within the treated segment, within the stent, and within its 5-mm proximal and distal edges. Patients treated with SESs had lower rates of binary (>50% diameter stenosis) angiographic restenosis within the segment (8.9% versus 36.3% with the BMS; P <0.001) and within the stent (3.2% versus 35.4% with the BMS; P <0.001). SESs were associated with significantly less late lumen loss within the treated segment, within the stent, and within its 5-mm proximal and distal edges (all P <0.001). The reduction of restenosis with the SES was consistent in patients at risk for restenosis, including those with small vessels, long lesions, and diabetes mellitus. The frequency of late aneurysms was similar in the 2 groups. Conclusions— Compared with BMSs, SESs reduced angiographic late lumen loss within the stent and its adjacent 5-mm margins in patients with complex native-vessel lesions.

Background— Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the “reintervention gap” between surgery and percutaneous intervention, making the percutaneous route preferable. Methods and Results— Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P <0.001). One-year major adverse events (defined as cardiac death, Q-wave and non–Q-wave myocardial infarction, or target vessel revascularization) was decreased 59% in the sirolimus-stent group (9.8% versus 24.9%; relative risk, 0.39; 95% CI, 0.26 to 0.61; P <0.001). Subgroup analysis of 135 patients with proximal LAD lesions showed similar benefits. In-stent restenosis was 0 in the proximal LAD sirolimus-eluting group (n=67), compared with 38% in the bare-metal arm (n=68), and major adverse events demonstrated a similar trend, with a 50% decrease compared with control patients (10.4% versus 20.6%, P =NS). Conclusions— Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.

Background— Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. Methods and Results— In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups ( P =0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo ( P =0.061 for intent-to-treat population). The primary reason for not completing treatment was ≥1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P <0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76±0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78±0.76 to 80 mm, P =0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm 3 , respectively; P =0.16 to 0.72). Conclusions— Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae.