Faculty Bibliography

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.

OBJECTIVES/OBJECTIVE:This study sought to update and validate a contemporary model for inpatient mortality following percutaneous coronary intervention (PCI), including variables indicating high clinical risk. BACKGROUND:Recently, new variables were added to the CathPCI Registry data collection form. This modification allowed us to better characterize the risk of death, including recent cardiac arrest and duration of cardiogenic shock. METHODS:Data from 1,208,137 PCI procedures performed between July 2009 and June 2011 at 1,252 CathPCI Registry sites were used to develop both a "full" and pre-catheterization PCI in-hospital mortality risk model using logistic regression. To support prospective implementation, a simplified bedside risk score was derived from the pre-catheterization risk model. Model performance was assessed by discrimination and calibration metrics in a separate split sample. RESULTS:In-hospital mortality was 1.4%, ranging from 0.2% among elective cases (45.1% of total cases) to 65.9% among patients with shock and recent cardiac arrest (0.2% of total cases). Cardiogenic shock and procedure urgency were the most predictive of inpatient mortality, whereas the presence of a chronic total occlusion, subacute stent thrombosis, and left main lesion location were significant angiographic predictors. The full, pre-catheterization, and bedside risk prediction models performed well in the overall validation sample (C-indexes 0.930, 0.928, 0.925, respectively) and among pre-specified patient subgroups. The model was well calibrated across the risk spectrum, although slightly overestimating risk in the highest risk patients. CONCLUSIONS:Clinical acuity is a strong predictor of PCI procedural mortality. With inclusion of variables that further characterize clinical stability, the updated CathPCI Registry mortality models remain well-calibrated across the spectrum of PCI risk.

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.

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:This study sought to examine whether rates of inappropriate percutaneous coronary intervention (PCI) differ by demographic characteristics and insurance status. BACKGROUND:Prior studies have found that blacks, women, and those who have public or no health insurance are less likely to undergo PCI. Whether this reflects potential overuse in whites, men, and privately insured patients, in addition to underuse in disadvantaged populations, is unknown. METHODS:Within the National Cardiovascular Data Registry CathPCI Registry, we identified 221,254 nonacute PCIs performed between July 2009 and March 2011. The appropriateness of PCI was determined using the Appropriate Use Criteria for coronary revascularization. Multivariable hierarchical regression was used to evaluate the association between patient demographics and insurance status and inappropriate PCI, as defined by the Appropriate Use Criteria. RESULTS:Of 211,254 nonacute PCIs, 25,749 (12.2%) were classified as inappropriate. After multivariable adjustment, men (adjusted odd ratio [OR]: 1.08 [95% CI: 1.05 to 1.11]; p < 0.001) and whites (adjusted OR: 1.09 [95% CI: 1.05 to 1.14]; p < 0.001) were more likely to undergo an inappropriate PCI in comparison with women and nonwhites. Compared with privately insured patients, those who had Medicare (adjusted OR: 0.85 [95% CI: 0.83 to 0.88]), other public insurance (adjusted OR: 0.78 [95% CI: 0.73 to 0.83]), and no insurance (adjusted OR: 0.56 [95% CI: 0.50 to 0.61]) were less likely to undergo an inappropriate PCI (p < 0.001). In addition, compared with urban hospitals, those admitted at rural hospitals were less likely to undergo inappropriate PCI, whereas those at suburban hospitals were more likely. CONCLUSIONS:For nonacute indications, PCIs categorized as inappropriate were more commonly performed in men, whites, and those who had private insurance. Higher rates of PCI in these patient populations may, in part, be due to procedural overuse.

Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary intervention. In an earlier consensus document, we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate (ADP) associated with post-percutaneous coronary intervention ischemic events for various platelet function tests (PFTs). Updated American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention, although routine testing is not recommended (Class III). Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor. Recent prospective randomized trials of PFT did not demonstrate clinical benefit, thus questioning whether treatment modification based on the results of current PFT platforms can actually influence outcomes. However, there are major limitations associated with these randomized trials. In addition, recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding. Therefore, a therapeutic window concept has been proposed for P2Y12 inhibitor therapy. In this updated consensus document, we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events. In addition, we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy.