Joseph Aragon

Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial.

CONTEXT High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined. OBJECTIVE To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. INTERVENTIONS High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. MAIN OUTCOME MEASURES The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days. RESULTS At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001). CONCLUSIONS Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00645918.

Stent fracture associated with drug‐eluting stents: Clinical characteristics and implications

Objective: To evaluate the clinical characteristics and implications of stent fracture in drug‐eluting stents. Background: Approximately 2.5 million drug‐eluting stents are implanted every year worldwide. In 10 randomized controlled trials involving 2,602 patients, no incidence of stent fracture was recognized or reported. Methods: From April 2003 to December 2005, 2,728 patients underwent drug‐eluting stenting. The angiograms of all 530 patients who underwent repeat angiography were analyzed to identify the presence of stent fracture. We then documented the incidence of adverse events associated with drug‐eluting stent fracture and systematically analyzed the clinical, procedural, and structural factors, which might predispose to stent fracture. Results: Stent fracture was identified in 10 patients. None of these fractures were detectable at the time of stent placement. The median time interval from stent implantation to detection of fracture at repeat angiography was 226 days (range, 7–620 days). Adverse clinical outcomes associated with stent fracture occurred in 7 patients (6 patients had binary restenosis and 1 patient had stent thrombosis), all necessitating repeat intervention. Analysis of potential predisposing clinical, procedural, and structural factors revealed that 4 patients had excessive tortuosity in the proximal segment, and overlapping stents were used in 5 cases. All fractures occurred in sirolimus‐eluting stents. Conclusions: Stent fracture may represent a new potential mechanism of restenosis and stent thrombosis in drug‐eluting stents. Predisposing clinical and procedural factors may be vessel tortuosity and use of overlapping stents. The most important predisposing factor, however, may be stent structure, since all fractures occurred in sirolimus‐eluting stents.

Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the U.S. transcatheter LAA ligation consortium

BACKGROUND Transcatheter left atrial appendage (LAA) ligation may represent an alternative to oral anticoagulation for stroke prevention in atrial fibrillation. OBJECTIVES This study sought to assess the early safety and efficacy of transcatheter ligation of the LAA for stroke prevention in atrial fibrillation. METHODS This was a retrospective, multicenter study of consecutive patients undergoing LAA ligation with the Lariat device at 8 U.S. sites. The primary endpoint was procedural success, defined as device success (suture deployment and <5 mm leak by post-procedure transesophageal echocardiography), and no major complication at discharge (death, myocardial infarction, stroke, Bleeding Academic Research Consortium bleeding type 3 or greater, or cardiac surgery). Post-discharge management was per operator discretion. RESULTS A total of 154 patients were enrolled. Median CHADS2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism [doubled]) was 3 (interquartile range: 2 to 4). Device success was 94%, and procedural success was 86%. A major complication occurred in 15 patients (9.7%). There were 14 major bleeds (9.1%), driven by the need for transfusion (4.5%). Significant pericardial effusion occurred in 16 patients (10.4%). Follow-up was available in 134 patients at a median of 112 days (interquartile range: 50 to 270 days): Death, myocardial infarction, or stroke occurred in 4 patients (2.9%). Among 63 patients with acute closure and transesophageal echocardiography follow-up, there were 3 thrombi (4.8%) and 13 (20%) with residual leak. CONCLUSIONS In this initial multicenter experience of LAA ligation with the Lariat device, the rate of acute closure was high, but procedural success was limited by bleeding. A prospective randomized trial is required to adequately define clinical efficacy, optimal post-procedure medical therapy, and the effect of operator experience on procedural safety.

Drug-eluting stenting is superior to bare metal stenting in saphenous vein grafts

This study compared the outcomes of percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) with drug‐eluting stents (DES) with bare metal stents (BMS). PCI of degenerated SVG is associated with worse outcomes and high incidence of in‐stent restenosis compared with PCI of native coronary arteries. There is a paucity of data on the outcomes of PCI of SVG with DES. Data from 223 consecutive patients who underwent PCI of SVG were imputed into a dedicated clinical database. We assessed the clinical outcomes at a mean follow‐up of 9.1 ± 2.1 months. A total of 139 patients underwent PCI of SVG with DES and 84 patients with BMS. The mean age of the SVG was 7.6 ± 3.8 years in the DES group and 7.7 ± 2.8 years in the BMS group (P = 0.38). Procedural success was achieved in all patients except for one patient in the BMS group who underwent emergent coronary artery bypass graft surgery for SVG dissection. There were no other in‐hospital cardiac events in both groups. There was one cardiac death in the DES group and three deaths in the BMS group (P = 0.03). When compared to the BMS, PCI of SVG with DES was associated with a lower incidence of myocardial infarction (4.3% vs. 20.2%; P = 0.04) and target vessel revascularization (10.1% vs. 36.9%; P = 0.035). When compared with BMS, PCI of SVG with DES was associated with a lower incidence of death, myocardial infarction, and target vessel revascularization.

Percutaneous left ventricular assist device: “TandemHeart” for high‐risk coronary intervention

Patients undergoing percutaneous coronary intervention (PCI) with severely compromised left ventricular systolic function and complex coronary lesions, including multivessel disease, left main disease, or bypass graft disease, are at higher risk of adverse outcomes from hemodynamic collapse. The TandemHeart percutaneous ventricular assist device may provide circulatory support during high‐risk PCI. We implanted the TandemHeart device in eight patients who underwent high‐risk PCI. The patients were considered to be at exceptionally high risk for decompensation due to procedural complexity combined with underlying LV dysfunction. The mean ejection fraction was 30% ± 9% and five patients were turned down for surgical revascularization. Seven patients underwent multivessel PCI, including three patients who underwent unprotected left main coronary artery PCI. There was 100% procedural success. The TandemHeart was removed immediately post‐PCI with no groin complications. Six patients are event‐ and symptom‐free at 189 ± 130 days; one patient died 10 days post‐PCI after lower extremity bypass surgery and another developed acute renal failure postprocedure, requiring hemodialysis. Our initial clinical experience with the TandemHeart ventricular assist device demonstrates that hemodynamic support can be rapidly achieved percutaneously during high‐risk PCI, with excellent procedural success in highly complex and critically ill patients.

Coronary sinus is dilated and outwardly displaced in patients with mitral regurgitation: quantitative angiographic analysis.

Our aim was to define the anatomy of the coronary sinus (CS) by venography. These measurements are essential in the selection of physical characteristics of percutaneous annuloplasty devices for mitral regurgitation (MR).

Comparison of Sirolimus-Eluting Stents With Paclitaxel-Eluting Stents in Saphenous Vein Graft Intervention (from a Multicenter Southern California Registry)

This study was designed to compare the safety and efficacy of sirolimus-eluting stents (SESs) to paclitaxel-eluting stents (PESs) in percutaneous intervention of saphenous vein graft (SVG) lesions. SVGs develop atherosclerosis at high rates and often require repeat revascularization. Percutaneous intervention with drug-eluting stents has become the preferred method of revascularization due to higher restenosis with bare metal stents and increased morbidity and mortality with repeat coronary artery bypass grafting. We sought to compare the rate of major adverse cardiac events and stent thrombosis between SESs and PESs in patients undergoing SVG intervention. A multicenter analysis of 172 patients with SVG lesions treated with SESs or PESs was performed. The 30-day and 1-year clinical outcomes of 102 patients receiving SESs were compared to those of 70 patients receiving PESs. There was no significant difference in baseline demographic, angiographic, and procedural characteristics between the SES and PES treatment groups. There was no statistical difference in major adverse cardiac events at 30 days and at 1 year (hazard ratio [HR] 1.58, 95% confidence interval [CI] 0.77 to 3.23, log-rank p = 0.21). There was also no difference in survival (HR 1.28, 95% CI 0.39 to 4.25, log-rank p = 0.69) or target vessel revascularization (HR 2.54, 95% CI 0.84 to 7.72, log-rank p = 0.09). In conclusion, this multicenter analysis of real-world patients demonstrated that SESs and PESs have similar clinical outcomes when used in SVG intervention.

Pimecrolimus and dual pimecrolimus-paclitaxel eluting stents decrease neointimal proliferation in a porcine model

The purpose of this study was to determine the effectiveness and vascular response of a pimecrolimus drug eluting stent and a combination (pimecrolimus + paclitaxel) stent as compared with bare metal controls in the porcine coronary model.

Impact of chronic renal insufficiency on clinical outcomes in patients undergoing saphenous vein graft intervention with drug-eluting stents: a multicenter Southern Californian Registry.

Objectives: To evaluate the clinical outcomes in patients with chronic renal insufficiency (CRI) who undergo saphenous vein graft (SVG) intervention with drug‐eluting stents (DES). Background: Patients with CRI have higher rates of major adverse cardiac events (MACE) after percutaneous revascularization. SVG intervention is associated with increased rates of MACE compared with percutaneous revascularization of native arteries. However, the impact of CRI on SVG intervention with DES has not been well delineated. Methods: Consecutive patients who underwent SVG intervention with DES at five medical centers from April 2003 to December 2007 were included in this analysis. Results: A total of 172 patients, 39 patients with CRI and a serum creatinine ≥1.5 mg dL−1, and 133 patients without CRI, underwent SVG intervention with DES. Patients with CRI were more often older, diabetic, and had a longer mean total stent length. At 1 year, patients with CRI had a higher MACE rate (35.9% vs. 15.8%, hazard ratio [HR] 2.48, 95% confidence interval [CI] 1.26–4.88, log rank P = 0.009), mainly driven by higher mortality (20.5% vs. 9.8%, HR 3.41, 95% CI 1.10–10.58, log rank P = 0.024). There was a trend toward higher rates of target vessel revascularization in the CRI group (21.8% vs. 10.3%, HR 2.42, 95% CI 0.94–6.24, log rank P = 0.059). Stent thrombosis rates were not different between patients with and without CRI (2.6% vs. 2.3%, P = 0.8). Multivariable analysis revealed that CRI was the only significant predictor of 1‐year MACE (HR 2.2, 95% CI 1.1–4.3; P = 0.03). Conclusions: Patients with CRI who underwent SVG intervention with DES had higher risks of MACE and death compared with patients with preserved renal function. Further treatment strategies are needed in this high‐risk group who undergo SVG intervention with DES.

Long-Term Outcomes of Elective Drug-Eluting Stenting of the Unprotected Left Main Coronary Artery in Patients with Normal Left Ventricular Function

To evaluate the early and long‐term outcomes of patients with normal left ventricular function who undergo elective unprotected left main coronary artery (ULMCA) percutaneous coronary intervention (PCI) with drug‐eluting stents (DES).