Faculty Bibliography

IMPORTANCE/OBJECTIVE:The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial. OBJECTIVE:To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Randomized, double-blind, active-controlled superiority trial that enrolled 13,229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection. INTERVENTIONS/METHODS:Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURES/METHODS:The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7. RESULTS:Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov Identifier: NCT01076764.

Women are at higher risk than men for bleeding and vascular complications after percutaneous coronary intervention (PCI). Compared with femoral access, radial access reduces these complications but may be more challenging in women because of higher rates of radial artery spasm, tortuosity, and occlusion as well as lower rates of procedure success. Whether the safety advantages of radial versus femoral access in women undergoing PCI are outweighed by reduced effectiveness has not been studied. The Study of Access site For Enhancement of PCI for Women is a prospective, randomized clinical trial comparing radial with femoral arterial access in women undergoing PCI. In conjunction with the US Food and Drug Administration's Critical Path Cardiac Safety Research Consortium, this study embeds the randomized clinical trial into the existing infrastructure of the National Cardiovascular Data Registry CathPCI Registry through the National Institute of Health's National Cardiovascular Research Infrastructure. The primary efficacy end point is a composite of bleeding (Bleeding Academic Research Consortium types 2, 3, or 5) or vascular complication requiring intervention occurring at 72 hours after PCI or by hospital discharge. The primary feasibility end point is procedure success. Secondary end points include procedure duration, contrast volume, radiation dose, quality of life, and a composite of 30-day death, vascular complication, or unplanned revascularization.

OBJECTIVES/OBJECTIVE:This study sought to develop a model that predicts bleeding complications using an expanded bleeding definition among patients undergoing percutaneous coronary intervention (PCI) in contemporary clinical practice. BACKGROUND:New knowledge about the importance of periprocedural bleeding combined with techniques to mitigate its occurrence and the inclusion of new data in the updated CathPCI Registry data collection forms encouraged us to develop a new bleeding definition and risk model to improve the monitoring and safety of PCI. METHODS:Detailed clinical data from 1,043,759 PCI procedures at 1,142 centers from February 2008 through April 2011 participating in the CathPCI Registry were used to identify factors associated with major bleeding complications occurring within 72 h post-PCI. Risk models (full and simplified risk scores) were developed in 80% of the cohort and validated in the remaining 20%. Model discrimination and calibration were assessed in the overall population and among the following pre-specified patient subgroups: females, those older than 70 years of age, those with diabetes mellitus, those with ST-segment elevation myocardial infarction, and those who did not undergo in-hospital coronary artery bypass grafting. RESULTS:Using the updated definition, the rate of bleeding was 5.8%. The full model included 31 variables, and the risk score had 10. The full model had similar discriminatory value across pre-specified subgroups and was well calibrated across the PCI risk spectrum. CONCLUSIONS:The updated bleeding definition identifies important post-PCI bleeding events. Risk models that use this expanded definition provide accurate estimates of post-PCI bleeding risk, thereby better informing clinical decision making and facilitating risk-adjusted provider feedback to support quality improvement.

OBJECTIVES/OBJECTIVE:The purpose of this study was to compare in-hospital outcomes of percutaneous coronary intervention (PCI) in extreme obesity (EO) (body mass index [BMI] ≥ 40 kg/m²) with those of normal-weight (NW) patients and to examine the influence of access site on outcomes. BACKGROUND:Little is known about the outcomes of PCI in EO patients. METHODS:We analyzed CathPCI Registry data from patients who underwent radial or femoral PCI and were discharged between July 2009 and June 2011 and compared in-hospital outcomes of EO (N = 83,861) with those of NW patients (BMI 20 to 25 kg/m²; N = 217,616). Outcomes included in-hospital mortality and procedural and bleeding complications. Multivariable logistic regression models were used to assess the independent association of EO with outcomes, using previously validated risk models derived from the CathPCI Registry. The role of access site was specifically examined. RESULTS:Compared with NW patients, EO patients were younger (median age 60 vs. 69 years), more likely female (47% vs. 37%), and more likely African American (12% vs. 7%). EO patients had lower unadjusted mortality (1.2% vs. 2.0%); however, after multivariable adjustment, EO was independently associated with increased risk of in-hospital mortality (odds ratio: 1.22; 95% CI: 1.08 to 1.39) in those presenting with ST-segment elevation myocardial infarction (STEMI). Access site had no effect on bleeding or outcome. CONCLUSIONS:EO patients who underwent PCI were younger and had less bleeding compared with NW patients. After multivariable adjustment for risk, EO was independently associated with higher in-hospital mortality overall and particularly in the patients undergoing STEMI.

BACKGROUND:New percutaneous coronary intervention (PCI) device technologies are often rapidly adopted into clinical practice, yet few studies have examined the overall impact of these new technologies on patient outcomes in community practice. METHODS:In hopes of determining temporal trends in PCI outcomes, we used data from the Centers for Medicare & Medicaid Service's Chronic Condition Warehouse (n = 3,250,836) by comparing patient characteristics and rates of 3-year major adverse cardiac events (MACE) across the balloon angioplasty (POBA) era (01/1991-09/1995), the bare metal stent (BMS) era (02/1998-04/2003), and the drug-eluting stent (DES) era (05/2004-10/2006). The adjusted association between era and outcomes was determined with Cox proportional hazards modeling (POBA era as reference). RESULTS:Compared with the POBA era, patients undergoing PCI were significantly older and had more medical comorbidities, and the risk for 3-year MACE was significantly lower during the BMS and DES eras (BMS vs. POBA adjusted HR [95% CI]: 0.930 [0.926-0.935]; DES vs. BMS: 0.831 [0.827-0.835]). Compared with males, the adjusted risk for 3-year MACE among females was lower during the POBA era, but slightly higher during the BMS and DES eras. Across all three eras, patients ≥75 years of age had higher adjusted risk for MACE compared with younger patients, and the risk for revascularization was lower for both females and older patients. CONCLUSIONS:Despite its application in older and sicker Medicare beneficiaries, there has been a significant decrease in post-PCI MACE over time. The risk for death or myocardial infarction is higher among females and older patients compared with males and younger patients; therefore, future studies should focus on improving clinical outcomes in these high-risk subgroups.

BACKGROUND:Bleeding is a common, noncardiac, preventable complication of percutaneous coronary intervention. We compared the relative safety of radial access and bivalirudin in percutaneous coronary intervention. METHODS AND RESULTS/RESULTS:From CathPCI Registry, we determined the association between the site of arterial access, bivalirudin, and periprocedural bleeding rates in 501 017 patients. Radial access patients receiving heparin (radial group) were compared with those receiving bivalirudin (radial combination group). Femoral access patients who had bivalirudin and a vascular closure device served as a reference group (femoral group). An inverse probability weighting analysis incorporating propensity scores was used to compare groups. The overall rate of bleeding was 2.59%. It was 2.71% in the femoral group, 2.5% in the radial group, and 1.82% in the radial combination groups (P<0.001). When compared with femoral group, the adjusted odds ratio for bleeding was significantly lower for patients with radial combination group (odds ratio, 0.79; 95% confidence interval, 0.72-0.86), but not for radial group (odds ratio, 0.96; 95% confidence interval, 0.88-1.05), unless patients treated with IIb/IIIa were excluded (radial group-IIb/IIIa odds ratio, 0.84; 95% confidence interval, 0.75-0.94).The number needed to treat to prevent 1 bleeding event with radial combination group was 138, whereas the number needed to treat to prevent 1 bleeding event in high-bleeding risk patients was 68. CONCLUSIONS:In this observational analysis, the combination of bivalirudin and radial access was associated with reduced bleeding event rate. This benefit was present across the entire spectrum of preprocedural risk of bleeding, with or without exposure to IIb/IIIa inhibitors. These data support an adequately powered randomized trial comparing bleeding avoidance strategies.

BACKGROUND:Studies examining the association between radial approach and post-percutaneous coronary intervention (PCI) bleeding and mortality have reached conflicting conclusions. There are no current data about the use and outcomes of transradial PCI (r-PCI) in the Veterans Affairs system. METHODS AND RESULTS/RESULTS:Consecutive veterans (n=24143 patients) undergoing PCI in the Veterans Affairs between 2007 and 2010 were examined. On the basis of propensity to undergo r-PCI, 3 cohorts matched with veterans undergoing transfemoral access were constructed among sites performing ≥ 1 r-PCI, ≥ 50 r-PCI (high volume), and <50 r-PCI (low volume). Cox proportional hazard models were used to determine the association between PCI access site, blood transfusion, and mortality. The prevalence of r-PCI increased over time (2007=2.1%; 2010=8.8%). Overall, there was no difference in procedure success between matched groups (r-PCI 97.3% versus transfemoral PCI 96.6%; P=0.182), or in the risk of postprocedure transfusion or mortality. Among matched patients treated at high r-PCI volume sites, radial access was associated with a decreased risk of post-PCI blood transfusion (hazard ratio, 0.4; 95% confidence interval, 0.3-0.7; P<0.001), and no significant difference in the risk of mortality (hazard ratio, 0.7; 95% confidence interval, 0.4-1.3; P=0.279). CONCLUSIONS:Within the Veterans Affairs, the use of r-PCI increased over time. r-PCI may be associated with a significant decreased risk of post-PCI blood transfusion among higher volume r-PCI sites. These data demonstrate that potential benefits of r-PCI in terms of reduced post-PCI blood transfusions may be more pronounced at sites that routinely use radial access.