Curtiss T. Stinis

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.

Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation

AIMS The aim of this study was to determine whether platelet reactivity on clopidogrel therapy, as measured by a point-of-care platelet function assay, is associated with thrombotic events after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). METHODS AND RESULTS Platelet reactivity on clopidogrel (post-treatment reactivity) was measured with the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA) in 380 patients undergoing PCI with sirolimus-eluting stents. Receiver-operating characteristic curve analysis was used to derive the optimal cut-off value for post-treatment reactivity in predicting 6 month out-of-hospital cardiovascular (CV) death, non-fatal MI, or stent thrombosis. The mean post-treatment reactivity was 184 +/- 85 PRU (P2Y12 reaction units). The optimal cut-off for the combined endpoint was a post-treatment reactivity > or =235 PRU [area under the curve 0.711 (95% confidence interval 0.529-0.893), P = 0.03], which was similar to the threshold of the upper tertile (231 PRU). Patients with post-treatment reactivity greater than the cut-off value had significantly higher rates of CV death (2.8 vs. 0%, P = 0.04), stent thrombosis (4.6 vs. 0%, P = 0.004), and the combined endpoint (6.5 vs. 1.0%, P = 0.008). CONCLUSION High post-treatment platelet reactivity measured with a point-of-care platelet function assay is associated with post-discharge events after PCI with DES, including stent thrombosis. Investigation of alternative clopidogrel dosing regimens to reduce ischaemic events in high-risk patients identified by this assay is warranted.

Zotarolimus-Eluting Peripheral Stents for the Treatment of Erectile Dysfunction in Subjects With Suboptimal Response to Phosphodiesterase-5 Inhibitors

OBJECTIVES This study sought to evaluate the safety and feasibility of zotarolimus-eluting stent implantation in focal atherosclerotic lesions of the internal pudendal arteries among men with erectile dysfunction (ED) and a suboptimal response to phosphodiesterase-5 inhibitors. BACKGROUND ED, a common condition, is often mediated by atherosclerosis. Current treatment options are limited. METHODS Male subjects with atherosclerotic ED and a suboptimal response to phosphodiesterase-5 inhibitors were enrolled in this prospective, multicenter, single-armed safety and feasibility trial. A novel combination of clinical, duplex ultrasound, and invasive angiographic factors were used to determine eligibility for stent therapy. The primary safety endpoint was any major adverse event 30 days after the procedure. The primary feasibility end point was improvement in the International Index of Erectile Function (Erectile Dysfunction Domain) score ≥ 4 points in ≥ 50% of subjects at 3 months. We report 6-month follow-up results, including duplex ultrasound and angiography. RESULTS Forty-five lesions were treated with stents in 30 subjects. Procedural success was 100% with no major adverse events through follow-up. The primary feasibility endpoint at 6 months was achieved by 59.3% of intention-to-treat subjects (95% confidence interval: 38.8% to 77.6%) and 69.6% of per-protocol subjects (95% confidence interval: 47.1% to 86.8%). Duplex ultrasound peak systolic velocity of the cavernosal arteries increased from baseline by 14.4 ± 10.7 cm/s at 30 days and 22.5 ± 23.7 cm/s at 6 months. Angiographic binary restenosis (≥ 50% lumen diameter stenosis) was reported in 11 (34.4%) of 32 lesions. CONCLUSIONS Among patients with ED and limited response with pharmacologic therapy, percutaneous stent revascularization of the internal pudendal artery is feasible and is associated with clinically meaningful improvement in both subjective and objective measures of erectile function.

A novel technique for ultra‐low contrast administration during angiography or intervention

Contrast‐induced nephropathy (CIN) after coronary angiography or intervention is associated with substantial morbidity. The data supporting various prophylactic measures and adjunctive therapies to prevent this complication are conflicting. However, contrast volume is clearly related to CIN after percutaneous coronary intervention (PCI), and the risk of CIN has been shown to be directly related to contrast dose. Therefore, minimizing contrast exposure is a primary method to reduce the risk of CIN, especially in at‐risk patients. We report a novel technique designed to deliver ultra‐low (<15 cm3) volume contrast to patients with chronic kidney disease undergoing coronary angiography and PCI.

Three-year outcome of drug-eluting stent implantation for coronary artery bifurcation lesions†

Objectives: To compare the very long‐term clinical outcomes of bifurcation lesions using the crush and the simultaneous kissing stent (SKS) techniques. Background: A variety of two‐stent techniques have been used to treat coronary artery bifurcation lesions in the drug‐eluting stent era, but the long‐term clinical outcome of these approaches is not known. Methods: A total of 74 consecutive patients underwent bifurcation stenting using either the crush or SKS techniques. Mean patient age was 66.91 ± 11.3 years; 26% were diabetic, and the left anterior descending/diagonal bifurcation was the most frequently treated lesion (68%). Results: In‐hospital outcomes were not significantly different between groups. Over a median follow‐up of 3.3 years, 1 patient in the SKS group and 3 patients in the crush group died (P = ns). Probable stent thrombosis leading to death according to the Academic Research Consortium definition occurred in 1 patient in the crush group. Mortality in the remaining 3 patients was noncardiac. Target lesion revascularization (TLR) occurred in 14 patients (40%) in the SKS group and 5 patients (12.8%) in the crush group (P = 0.015). Survival free from major adverse cardiac events (MACE) was significantly less in the SKS group and predominantly driven by TLR (60 vs. 88%, P = 0.001). Conclusions: In conclusion, over a median of 3.3 years of follow‐up, TLR and MACE are significantly lower in bifurcation lesions treated with the crush technique when compared with the SKS technique. Definite or probable stent thrombosis is rare with either technique.

Clinical outcomes following predilation with a novel 1.25-mm diameter angioplasty catheter†

Objective: An unmet need is represented in angioplasty catheters that permit the predilation stage of treating complex coronary anatomy oftentimes not amenable to conventional device therapies. Background: Lesion preparation with balloon angioplasty prior to stent placement remains the most common method of percutaneous coronary revascularization. Methods: Clinical and angiographic outcomes were evaluated following a treatment strategy of coronary artery disease that included predilation with a low‐profile, 1.25‐mm angioplasty catheter prior to stent placement. The study primary end point of procedural success was defined as successful device delivery and lesion treatment, including the absence of clinically significant perforation, arrhythmia, flow‐limiting dissection, or reduction in baseline Thrombolysis In Myocardial Infarction (TIMI) grade with final achievement of TIMI 3 flow. Results: Among 51 patients (54 lesions), predilation using a 1.25 mm angioplasty catheter was associated with procedural and device‐related success rates of 100%. In‐hospital target lesion failure occurred in one patient (2.0%) related to postprocedural myocardial infarction. Patient and angiographic characteristics included diabetes, 43.1%; lesion length ≥20 mm, 20.4%; bifurcation lesion, 31.5%; lesion classification B2/C, 74.1%; and baseline TIMI 0/1 flow, 13.0%. No subsequent in‐hospital adverse events occurred. Conclusions: Percutaneous coronary revascularization involving a predilation strategy with a low profile, 1.25‐mm angioplasty catheter is associated with favorable procedural safety and efficacy and may represent an effective initial treatment for complex coronary anatomy.

Clinical outcomes of endovascular treatment of TASC-II C and D femoropopliteal lesions with the Viabahn endoprosthesis ☆

OBJECTIVES The objective of this study was to evaluate clinical outcomes and patency rates using the Viabahn endoprosthesis in complex (TASC-II C and D) femoropopliteal lesions. BACKGROUND Traditional treatment of symptomatic TASC-II C and D femoropopliteal lesions has mainly centered on open surgical options in patients deemed appropriate candidates. Endovascular treatment of these lesions with balloon angioplasty has been historically hampered by aggressive restenosis and relatively early clinical failure. The Viabahn endoprosthesis was developed with the intent of reducing restenosis while improving overall flexibility in the femoropopliteal segment. METHODS Between March 2009 and July 2011 a total of 51 limbs in 41 patients underwent implantation of one or more Viabahn endovascular stent grafts for the treatment of symptomatic TASC-II C or D lesions. Patients were followed clinically at regular intervals and also underwent routine surveillance duplex ultrasound at 1, 3, 6, and 12 months post-procedure. The average follow-up from the index procedure was 14.6 months (range 13-35.2 months). RESULTS A total of 22 TASC-II C and 29 TASC-II D lesions were treated (51 limbs in 41 patients). The mean lesion length was 22.4 cm. The overall 1-year primary patency rate was 74.8% (95% CI: 61.2%-88.4%), assisted primary patency rate was 87.4% (95% CI: 70.9%-95.9%), and the secondary patency rate was 94.9% (95% CI: 88.0%-100.0%). CONCLUSIONS The Viabahn endoprosthesis is a safe and effective option for the treatment of TASC-II C and D femoropopliteal lesions. Patency rates are favorable despite the complexity of these lesions, although multiple endovascular re-interventions may be necessary to achieve an acceptable long-term result.

Risk Assessment in Patient Selection for Transcatheter Aortic Valve Replacement

Risk assessment models for transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement in high-risk patients and TAVR versus palliation in inoperable patients are based on surgical data and have limited discrimination and calibration in the setting of TAVR. Several novel risk models specifically designed for TAVR have improved discrimination over existing models but require further validation. Several clinical and echocardiographic variables, such as chronic lung disease, mitral regurgitation, and stroke volume index, influence outcomes. This article reviews current and novel risk models and important predictors of TAVR outcomes and proposes a framework to integrate them into clinical decision-making for patients with severe, symptomatic aortic stenosis.

Use of intravascular ultrasound to guide endovascular repair of popliteal artery aneurysms

To evaluate the outcomes of intravascular ultrasound (IVUS) directed endovascular exclusion of popliteal artery aneurysm (PAA) using stent grafts.

Closure for arterial access in balloon aortic valvuloplasty

In this issue, O’Neil et al. present retrospective data analyzing the outcomes of the “pre-closure” technique using two Proglide suture-mediated devices (Abbott Laboratories, Redwood City, CA) to achieve hemostasis in patients undergoing balloon aortic valvuloplasty (BAV). Their data show that utilization of the “pre-closure” technique (in the setting of bivalirudin anticoagulation for the majority of patients) appears to decrease acute vascular complications and bleeding. Moreover, use of the “preclosure” technique was associated with lower rates of death and myocardial infarction, which translated into lower rates of major adverse cardiac events and lower net adverse cardiovascular events. When examining the data in greater depth, however, several important points must be considered. First, this was not a randomized study, and the decision to use the “pre-closure” technique was entirely up to the discretion of the operators. Second, there are important statistically significant differences between the groups. As compared with patients who underwent arterial closure with the “pre-closure” technique, patients who were treated with manual compression of the arteriotomy site were more likely to have been treated with bivalirudin as opposed to heparin (60.6% vs. 37.7%), had more underlying peripheral arterial disease (30.8% vs. 20.1%), had undergone more previous BAV procedures (10.7% vs. 3.9%), underwent BAV with larger balloon sizes (possibly requiring larger sheaths) (22 mm vs. 21.6 mm), and underwent more rapid ventricular pacing (which could potentially contribute to myocardial ischemia and worse clinical outcomes). Despite these important considerations, however, the data suggest a potential benefit to the “pre-closure” technique in the setting of BAV, and clearly further studies designed to specifically compare the use of the “pre-closure” technique to manual compression in a more controlled way are in order. The “pre-closure” technique using two Proglide devices, the Prostar suture-mediated closure device (Abbott Laboratories), and the Angioseal collagenbased closure device (St. Jude Medical, Minneapolis, MN) are the current vascular closure devices used for hemostasis in BAV. A recent analysis of bleeding comparing manual compression to the Angioseal and “preclosure” techniques demonstrated fewer complications when using vascular closure devices [1]. The “preclosure” technique had the greatest number of technical failures (12%) in this analysis, but the rate of major vascular complications remained similar across all three treatment groups (5.5–6.7%). Those who have experience using the Proglide device and with performing the “pre-closure” technique will appreciate that there is a definite technical learning curve in becoming proficient at using the device, and this needs to be considered when designing future studies and analyzing the resultant data. Individual analysis and meta-analysis have shown no difference with respect to bleeding or cardiovascular outcomes when examining vascular closure device data in the context of coronary interventions [2]. Although the series presented here by O’Neil et al. demonstrated less bleeding with closure device usage, the fact that most of the “pre-closure” cases utilized bivalirudin cannot be discounted because bivalirudin was associated with a 36% reduction in major bleeding when used during acute myocardial infarction [3]. Moreover, post hoc analysis of the Acute Catheterization and Urgent Intervention Triage Strategy trial showed an association between vascular closure devices, bivalirudin use, and decreased bleeding—similar to the outcomes described in this manuscript [4]. Perhaps, the retrospective data shown here may lay a roadmap to using more bivalirudin in structural interventions, especially those with large-bore arterial access. Anatomic selection for vessel access plays a significant role in avoiding complications. Technical success of the Proglide suture-mediated device is predicted to have an adequate vessel lumen, uncomplicated single anterior puncture technique, and uncalcified vessel