David R. Rutledge

Contemporary Incidence and Predictors of Stent Thrombosis and Other Major Adverse Cardiac Events in the Year After XIENCE V Implantation: Results From the 8,061-Patient XIENCE V United States Study

OBJECTIVES The aim of this study was to identify predictors of clinical events after XIENCE V (Abbott Vascular, Santa Clara, California) stenting. BACKGROUND The XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval) study is a prospective, multicenter, Food and Drug Administration-required post-approval study to examine safety and effectiveness in real-world settings. After an initial 5,062 patients, 2,999 more were included as part of the DAPT (Dual Antiplatelet Therapy) trial (total n = 8,061). METHODS One-year clinical events, including stent thrombosis (ST), cardiac death/myocardial infarction (MI), target lesion failure, and target lesion revascularization, were adjudicated according to Academic Research Consortium criteria, with ST and cardiac death/MI as primary and co-primary endpoints. Demographic, clinical, and procedural variables were assessed by multivariable analysis. A time-dependent covariate assessed the association between DAPT usage and ST. RESULTS Roughly 61% were off-label; 85.6% remained on DAPT without interruption through 1 year. Incidences of definite/probable ST, cardiac death/MI, target lesion failure, and target lesion revascularization were 0.80% (95% confidence interval [CI]: 0.61% to 1.03%), 7.1% (95% CI: 6.51% to 7.68%), 8.9% (95% CI: 8.30% to 9.60%), and 4.3% (95% CI: 3.82% to 4.75%), respectively. Several independent clinical and angiographic predictors were identified for each outcome. Predictors of ST included DAPT interruption ≤ 30 days (hazard ratio [HR]: 8.63, 95% CI: 2.69 to 27.73, p = 0.0003), renal insufficiency (HR: 3.72, 95% CI: 1.71 to 8.09, p = 0.0009), and total stent length (HR: 1.30, 95% CI: 1.16 to 1.47, p < 0.0001). A DAPT interruption >30 days was not predictive of ST. CONCLUSIONS In this large, real-world population, XIENCE V demonstrated low event rates at 1 year, with several independent predictors. Early DAPT interruption (≤ 30 days) was the most potent predictor of ST, whereas delayed interruption (>30 days) was not predictive. (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval Study; NCT00676520).

Stent Thrombosis and Dual Antiplatelet Therapy Interruption with Everolimus-Eluting Stents: Insights from the Xience v Coronary Stent System Trials

Background—Whether premature dual antiplatelet therapy (DAPT) interruption is safe in patients receiving cobalt chromium everolimus–eluting stents remains controversial. We sought to examine the relationship between DAPT discontinuation and stent thrombosis (ST) after cobalt chromium everolimus-eluting stents. Methods and Results—Outcomes from 11 219 patients were pooled from 3 randomized trials and 4 registries with 2-year follow-up period after cobalt chromium everolimus–eluting stent implantation. Rates of definite/probable ST were analyzed according to DAPT discontinuation in the following time intervals: 0 to 30, 30 to 90, 90 to 180, 180 to 365, and 365 to 730 days. Eighty-five cases of ST (0.75%) occurred in 83 patients during 2 years, with 41 (48.2%) events occurring within 30 days. The 2-year ST rate in patients interrupting DAPT at any time was similar to that in patients never interrupting DAPT through 2 years (25/4067 [0.63%] versus 58/7152 [0.83%] respectively; P=0.27]. By propensity and DAPT usage–adjusted multivariable analysis, permanent DAPT discontinuation before 30 days was independently associated with the occurrence of ST (hazard ratio [95% confidence interval], 26.8 [8.4–85.4]; P<0.0001), whereas permanent DAPT discontinuation in any interval after 90 days was not associated with ST. Only 2 ST events occurred after DAPT discontinuation between 30 and 90 days (both between 30 and 60 days), and the association between permanent DAPT discontinuation and ST during this period is unclear (hazard ratio [95% confidence interval], 8.7 [2.0–37.3]; P=0.004 for adjusted analysis and 3.4 [0.8–13.8]; P=0.07 for the unadjusted analysis). Conclusions—In this large pooled experience, permanent DAPT discontinuation before 30 days after cobalt chromium everolimus–eluting stent implantation was strongly associated with ST, whereas DAPT discontinuation beyond 90 days appeared safe. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180310, NCT00180479, NCT00307047, NCT00402272, NCT00496938, NCT00676520, and NCT00631228.

Safety and Effectiveness of Everolimus-Eluting Stents in Chronic Total Coronary Occlusion Revascularization: Results From the EXPERT CTO Multicenter Trial (Evaluation of the XIENCE Coronary Stent, Performance, and Technique in Chronic Total Occlusions)

OBJECTIVES This study sought to evaluate procedural and clinical outcomes among patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using contemporary methods and everolimus-eluting stents (EES). BACKGROUND Limited studies have detailed the procedural and late-term safety and efficacy of CTO revascularization among multiple centers applying modern techniques and with newer-generation drug-eluting stents. METHODS Among 20 centers, 250 consecutive patients were enrolled for attempted CTO PCI. Procedural and in-hospital clinical outcomes were examined in addition to the 1-year primary endpoint of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events [MACE]). RESULTS Demographic, lesion, and procedural characteristics included prior bypass surgery: 9.9%; diabetes: 40.1%; lesion length: 36.1 ± 18.5 mm; and stent length: 51.7 ± 27.2 mm. Procedural success, defined as guidewire recanalization with no in-hospital MACE, was 96.4%. Success with antegrade-only methods was 97.9% and 86.2% by retrograde/combined methods, respectively. Compared with a pre-specified performance goal derived from 6 prior CTO drug-eluting stent trials (1-year MACE: 24.4%), treatment with EES was associated with significantly lower composite adverse events for both intent-to-treat (18.5%, 1-sided upper confidence interval: 23.4%, p = 0.025) and per-protocol populations (8.2%, 1-sided upper confidence interval: 12.3%, p < 0.0001). Target lesion revascularization at 1 year was 6.3%. Dual antiplatelet therapy adherence was 53.9% at 1 year, yet subacute definite stent thrombosis occurred in only 2 patients (0.9%), and late probable stent thrombosis occurred in 1 patient (0.5%). CONCLUSIONS In a multicenter registration trial representing contemporary technique and EES, favorable procedural success and late-term clinical outcomes support CTO PCI in a patient population with high lesion complexity. (EXPERT CTO: Evaluation of the XIENCE PRIME LL and XIENCE Nano Everolimus Eluting Coronary Stent Coronary Stents, Performance, and Technique in Chronic Total Occlusions; NCT01435031).

SPIRIT Women, evaluation of the safety and efficacy of the XIENCE V everolimus-eluting stent system in female patients: referral time for coronary intervention and 2-year clinical outcomes

AIMS SPIRIT Women is the first interventional trial dedicated exclusively to women, focusing on symptoms at presentation, referral time to coronary intervention and the safety and performance of the XIENCE V stent. METHODS AND RESULTS SPIRIT Women is a prospective, open-label, multicentre study in which 1,573 women were enrolled at 73 sites outside the United States. The primary endpoint is the composite of all death, Academic Research Consortium (ARC) defined myocardial infarction (MI) and target vessel revascularisation (TVR) at one year. Data collected included symptoms at presentation and referral to coronary intervention. To allow comparison by gender, the latter were compared to data from male patients from the SPIRIT V study. The one- and two-year composite of all death, MI and TVR was 12% and 15%, respectively. Target lesion revascularisation (TLR) and stent thrombosis (definite and probable) rates were 2.4% and 0.59%, respectively, at one year and 3.6% and 0.73%, at two years. The total referral time for coronary intervention in women was four days longer than for men in the SPIRIT V study. CONCLUSIONS The XIENCE V stent is safe and effective with low TLR and stent thrombosis rates. More efforts remain to be made to increase the awareness of women and physicians of the risk for coronary artery disease (CAD).

Clinical outcomes in real‐world patients with small vessel disease treated with XIENCE V® everolimus‐eluting stents: One year results from the XIENCE V® USA condition of approval post‐market study

The purpose of this study was to evaluate the 1‐year clinical outcomes of more complex XIENCE V USA real‐world patients with small versus nonsmall vessel lesions.

Clinical outcomes in real-world patients with acute myocardial infarction receiving XIENCE V® everolimus-eluting stents: one-year results from the XIENCE V USA study.

The objective of this analysis was to evaluate the safety and effectiveness of XIENCE V in acute myocardial infarction (AMI).

TransRadial Education And Therapeutics (TREAT): Shifting the balance of safety and efficacy of antithrombotic agents in percutaneous coronary intervention: A report from the Cardiac Safety Research Consortium

Percutaneous coronary intervention (PCI) is an integral part of the treatment of coronary artery disease. The most common complication of PCI, bleeding, typically occurs at the vascular access site and is associated with short-term and long-term morbidity and mortality. Periprocedural bleeding also represents the primary safety concern of concomitant antithrombotic therapies essential for PCI success. Use of radial access for PCI reduces procedural bleeding and hence may change the risk profile and net clinical benefit of these drugs. This new drug-device safety interaction creates opportunities to advance the safe and effective use of antithrombotic agents during PCI. In June 2010 and March 2011, leaders from government, academia, professional societies, device manufacturing, and pharmaceutical industries convened for 2 think tank meetings. Titled TREAT I and II, these forums examined approaches to improve the overall safety of PCI by optimizing strategies for antithrombotic drug use and radial artery access. This article summarizes the content and proceedings of these sessions.

Clinical outcomes in real-world patients with bifurcation lesions receiving Xience V everolimus-eluting stents: Four-year results from the Xience V USA study

The Xience V USA Study demonstrated safety and efficacy of the XIENCE V® everolimus‐eluting stent (EES) in a large, prospective study of a real‐world, unselected patient population. There is limited long‐term data regarding EES performance in high risk patients with bifurcation lesions (BIF). The objective of this analysis was to evaluate the long‐term safety and effectiveness of EES in patients with BIF from the XIENCE V USA study.

Sustained Low Clinical Event Rates in Real-World Patients Receiving Everolimus-Eluting Coronary Stent System from a Large, Prospective, Condition of Approval Study: 2-Year Clinical Outcomes from the XIENCE V® USA Study

OBJECTIVES This 2-year follow-up of the XIENCE V USA study examines both the long-term safety and effectiveness of the everolimus-eluting coronary stent system (EECSS) in real-world patients. BACKGROUND The safety and effectiveness of EECSS at 1 year in real-world clinical settings have been demonstrated in XIENCE V USA trial with low rates of target lesion revascularization (TLR), cardiac death, myocardial infarction (MI), and stent thrombosis (ST). Data on whether efficacy is maintained after 1 year and the event rate of very late stent thrombosis (VLST) between 1 and 2 years have not yet been reported. METHODS XIENCE V USA is a prospective, multicenter, single-arm, FDA required condition of approval study designed to examine the safety and effectiveness of EECSS in an all-inclusive, consecutively enrolled population from real-world clinical settings. Clinical end-point events, including ST, cardiac death, MI, and revascularization were adjudicated by an independent Clinical Events Committee. RESULTS  Four thousand eight hundred and seventy-three (96.4%) out of 5,054 participants (1,875 standard-risk; 3,059 extended-risk) reached 2-year follow-up. The 2-year rate of Academic Research Consortium (ARC)-defined definite and probable ST was 0.96% (95% CI 0.70-1.28) in the overall population and 0.34% (95% CI 0.12-0.74) and 1.33% (95% CI 0.95-1.81) in the standard-risk and extended-risk cohorts, respectively. The rate of VLST was 0.06% in the overall population, 0.0% in the standard-risk, and 0.10% in the extended-risk cohorts. The 2-year composite rate of cardiac death and ARC-defined MI was 8.9% (95% CI 8.08-9.70) in the overall population and 5.6% (95% CI 4.61-6.78) and 10.8% (95% CI 9.71-11.94) in the standard-risk and extended-risk cohorts, respectively. CONCLUSION Low event rates observed at 1 year were maintained through 2 years. Despite the increased number of patients who discontinued dual antiplatelet therapy by 2 years, the ST rate remained consistently low, and <1% at 2 years due to low VLST occurrence. These results demonstrate continued safety and effectiveness of the XIENCE V everolimus-eluting stent in a highly complex, real-world patient population through 2 years.

Clinical outcomes in real-world patients with small vessel disease treated with XIENCE V ® everolimus-eluting stents

The purpose of this study was to evaluate the 1‐year clinical outcomes of more complex XIENCE V USA real‐world patients with small versus nonsmall vessel lesions.