Faculty Bibliography

OBJECTIVES: We sought to examine angiographic and clinical outcomes with sirolimus-eluting stents (SES) in total coronary occlusion (TCO) revascularization. BACKGROUND: Despite evaluation of drug-eluting stents beyond approved indications, few studies have evaluated their clinical benefit in TCO revascularization. METHODS: Among 15 centers in North America, 200 consecutive TCO patients (78.8% >6 weeks TCO age) were enrolled for treatment with SES. The primary end point was 6-month angiographic binary restenosis within the treated segment. RESULTS: Patient characteristics included: diabetes, 24.5%; prior infarction, 33.5%; and stent length, 45.9 mm median (quartile 1, 30.2 mm; quartile 2, 62.1 mm). A total of 199 patients (99.5%) were treated with SES, and procedural success was 98.0%. The 6-month binary restenosis rates were 9.5% in-stent, 12.4% in-segment, and 22.6% in-"working length" representing the entire treatment segment. Rates of 1-year target lesion revascularization, myocardial infarction, and target vessel failure were 9.8%, 1.0%, and 10.9%, respectively. Stent thrombosis occurred in 2 patients (1.0%). Using logistic regression modeling with propensity score adjustment, the absolute reduction in binary restenosis with SES compared with a historical bare-metal stent control was 37.7% (95% confidence interval [CI]: 27.2% to 48.3%, p < 0.001; odds ratio: 0.17, 95% CI: 0.09 to 0.30, p < 0.0001). Among 32 patients (16%) identified with stent fracture, target lesion revascularization was more common than patients without fracture (25.0% vs. 6.7%, p = 0.005). CONCLUSIONS: Despite greater lesion complexity than prior TCO trials, percutaneous revascularization with SES appears safe and results in substantial reductions in angiographic restenosis and failed patency and a low rate of repeat revascularization. These findings support the use of SES in TCO revascularization. (The ACROSS/TOSCA Trial; NCT00378612).

OBJECTIVE:To evaluate the burden of major bleed in patients with non-ST segment elevation acute coronary syndromes (NSTE ACS) receiving injectable anticoagulation from the hospital perspective. METHODS:Retrospective analysis of inpatient medical and pharmacy data from the Premier Perspective Comparative Database between 1/1/2003 and 3/31/2006. Hospitalized patients aged >or=18 years with a diagnosis of UA or NSTEMI who received an injectable anticoagulant agent during the same hospital stay were stratified into two cohorts: those who experienced a major bleed during hospitalization and those who did not, defined by the presence of >or=1 pre-specified ICD-9 codes. Length of hospital stay (LOS), inpatient mortality, 30-day readmissions, and hospitalization costs over 30 days were assessed between the cohorts using statistical models to control for covariates which may have impacted the outcomes. RESULTS:Patients with a major bleed had significantly longer length of stay (13.8 days vs 5.6 days), higher readmission rates (31.3% vs 14.7%), and increased all-cause mortality (15.0% vs 4.5%) compared with patients who did not bleed. After controlling for covariates, major bleeding was significantly associated with increased length of stay, readmission rate, and mortality. Adjusted costs were $13,856 higher on average for patients with a major bleed (95% CI: $13,828-$18,884; p < 0.0001). Subanalyses conducted on patients aged >or=65 years and those undergoing invasive procedures demonstrated higher occurrence of bleed than the general population and a similar impact on outcomes assessed. CONCLUSION/CONCLUSIONS:In conclusion, the study showed that patients with UA or NSTEMI who experience a major bleed have significantly longer hospital stays, higher readmission rates, increased costs, and increased mortality than those without a major bleed. These data emphasize the importance of considering the safety profile in context of the efficacy of the recommended agents. The findings from this study are limited by the retrospective study design and certain endpoints, such as readmissions, may have been underreported.

Published mortality models for percutaneous coronary intervention (PCI), including the Clinical Outcomes Assessment Program (COAP) model, have not considered the effect of out-ofhospital cardiac arrest. The primary objective of this study was to determine if the inclusion of out-of-hospital cardiac arrest altered the COAP mortality model for PCI. The COAP PCI database contains extensive demographic, clinical, procedural and outcome information, including out-of-hospital cardiac arrest, which was added to the data collection form in 2006. This study included 15,586 consecutive PCIs performed in 31 Washington State hospitals in 2006. Using development and test sets, the existing COAP PCI logistic regression mortality model was examined to assess the effect of out-of-hospital arrest on in-hospital mortality. Overall, 2% of individuals undergoing PCI had cardiac arrest prior to hospital arrival. Among 8 hospitals with PCI volumes < 120 cases per year, 4 had cardiac arrest volumes that exceeded 10% of total volume, whereas none of the centers with > 120 cases per year did. In-hospital mortality was 19% in the arrest group and was 1.0% in remaining procedures (p < 0.0001). In the new multivariate model, out-of-hospital cardiac arrest was highly associated with mortality (odds ratio = 5.50; 95% confidence interval [CI] = 3.28-9.25). When evaluated in the test set, the new model had excellent discrimination (c-statistic = 0.89; 95% CI = 0.85-0.93). Out-of-hospital cardiac arrest is an important determinant of risk-adjusted in-hospital mortality for PCI, particularly for hospitals with low volumes and relatively high volumes of cardiac arrest cases.

Definitions of bleeding must be considered when evaluating results of clinical trials. Assessments of bleeding impact based on clinical criteria may be more relevant to patient outcomes than those based on simple laboratory measures like an isolated change in hemoglobin, that do not appear to affect patient care. The risk of excessive bleeding in patients who receive antiplatelet and antithrombotic therapy is related to a combination of patient characteristics (older age, female sex, impaired renal function), and delivery factors (excessive dosing, stacking of anticoagulants). Investigators should justify components of bleeding endpoints as being clinically meaningful, sufficiently frequent in the study population, and affected by the intervention.

BACKGROUND:Bleeding among patients with acute myocardial infarction (AMI) is associated with worse long-term outcomes. Although the mechanism underlying this association is unclear, a potential explanation is that withholding antiplatelet therapies long beyond resolution of the bleeding event may contribute to recurrent events. METHODS AND RESULTS/RESULTS:We examined medication use at discharge, 1, 6, and 12 months after AMI among 2498 patients in the Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER) registry. Bleeding was defined as non-coronary artery bypass graft-related Thrombolysis of Myocardial Infarction major/minor bleeding or transfusion among patients with baseline hematocrit > or =28%. Logistic regression was used to evaluate the association between bleeding during the index AMI hospitalization and medication use. In-hospital bleeding occurred in 301 patients (12%) with AMI. Patients with in-hospital bleeding were less likely to be discharged on aspirin or thienopyridine (adjusted odds ratio=0.45; 95% CI, 0.31 to 0.64; and odds ratio=0.62; 95% CI, 0.42 to 0.91, respectively). At 1 month after discharge, although patients with in-hospital bleeding remained significantly less likely to receive aspirin (odds ratio=0.68; 95% CI, 0.50 to 0.92), use of thienopyridines in the 2 groups started to become similar. By 1 year, antiplatelet therapy use was similar among patients with and without bleeding. Postdischarge cardiology follow-up was associated with greater antiplatelet therapy use than either primary care or no clinical follow-up. CONCLUSIONS:Patients whose index AMI is complicated by bleeding are less likely to be treated with antiplatelet therapies during the first 6 months after discharge. Early reassessment of antiplatelet eligibility may represent an opportunity to reduce the long-term risk of adverse outcomes associated with bleeding.

The optimal duration of clopidogrel administration after percutaneous coronary intervention (PCI) remains unknown. Clopidogrel is currently recommended for minimums of 1 and 12 months after bare-metal stent and drug-eluting stent implantation, respectively. To determine the impact of clopidogrel discontinuation 1 year after PCI, the outcomes of 530 consecutive patients who underwent PCI from January 2004 to July 2006, were free of cardiovascular events for 6 months after PCI, and had follow-up available for >12 months were examined. The outcomes of patients who received clopidogrel for > or =1 year were compared with those of patients who received it for <1 year. The mean age was 65 +/- 9 years. Patients often presented with acute coronary syndromes (57%), and 85% received drug-eluting stents. Clopidogrel was used for > or =1 year and for <1 year in 341 and 189 patients, respectively. During a mean follow-up period of 2.4 +/- 0.8 years, 40 patients (8%) died, 21 (4%) had acute myocardial infarctions, and 89 (17%) underwent repeat coronary revascularization. Compared with patients with clopidogrel administration for <1 year after PCI, those who received clopidogrel for > or =1 year had lower mortality (14.8% vs 3.5%, p <0.001). On multivariate analysis, clopidogrel use for > or =1 year was associated with lower mortality (hazard ratio 0.28, 95% confidence interval 0.14 to 0.59), independent of traditional cardiovascular risk factors, clinical presentation, and the use of drug-eluting stents. In conclusion, the use of clopidogrel for > or =1 year after PCI was associated with lower mortality.

BACKGROUND:Short-term use of clopidogrel plus aspirin among patients with acute coronary syndrome reduces ischemic events, but concerns about coronary artery bypass graft (CABG) surgery-related bleeding limit its early use. METHODS:Using data from 4,794 consecutive CABG procedures in the Duke Databank for Cardiovascular Disease (January 1999 to December 2003), we developed multivariable models for associations with CABG-related bleeding defined as reoperation for bleeding, red cell transfusion, and a composite of reoperation/transfusion/hematocrit drop>or=15%. We examined clopidogrel use<or=5 days versus no clopidogrel<or=5 days before CABG in each model. Models were adjusted for propensity for clopidogrel use<or=5 days. RESULTS:Of 4,794 CABG patients, 332 (6.9%) received clopidogrel<or=5 days before CABG, 127 (2.6%) had reoperation for bleeding, 3,277 (68.4%) received red cell transfusion, and 4,387 (91.5%) had the composite outcome. After adjustment, clopidogrel use<or=5 days was not significantly associated with reoperation (odds ratio [OR] 1.24, 95% CI 0.63-2.41) or the composite end point (OR 1.23, 95% CI 0.72-2.10). Clopidogrel<or=5 days was modestly associated with red cell transfusion (OR 1.40, 95% CI 1.04-1.89) but more weakly than other factors, including which surgeon performed the procedure. CONCLUSION/CONCLUSIONS:Clopidogrel administration<or=5 days before CABG was not significantly associated with reoperation for bleeding or a bleeding composite, and only weakly with red cell transfusion after surgery. The impact of withholding clopidogrel acutely in those for whom clopidogrel has proven benefits and the impact of delaying CABG to prevent bleeding among patients treated with clopidogrel should be viewed in the context of other stronger determinants of bleeding.

BACKGROUND:Clinical trials of drug-eluting stents (DES) vs bare metal stents (BMS) report a reduced need for target lesion revascularization with no difference in death or myocardial infarction. However, these trials selectively enrolled patients with lower risk, single-vessel coronary artery disease (CAD) and limited the follow-up period to 1 year or less. Thus, it is not known how these short-term results apply to patients with higher risk, multivessel CAD seen in community practice settings. The objective of this study was to compare the long-term clinical outcomes of patients receiving DES vs BMS in a clinical practice setting. METHODS:Patients from the Duke Databank for Cardiovascular Disease undergoing their initial revascularization with DES or BMS from January 1, 2000, through July 31, 2005, were included in the study population. Propensity scores and inverse probability weighted estimators were used to adjust for treatment group imbalances. RESULTS:The study population included 1501 patients who received DES and 3165 who received BMS. After adjustment, DES reduced target vessel revascularization (TVR) rates at 6, 12, and 24 months compared with BMS (24-month rates: DES, 6.6%; BMS, 16.3%; difference, -9.7%; 95% confidence interval [CI], -11.7% to -7.7%; P < .001). The TVR benefit for DES increased among patients with multivessel CAD (1-vessel CAD: -8.3%; 95% CI, -10.9% to -5.8%; P < .001; 2-vessel CAD: -9.7%; 95% CI, -3.6% to -5.8%; P < .001; 3-vessel CAD: -16.2%; 95% CI, -25.2% to -7.2%; P < .001). However, in the overall cohort there were no statistically significant differences in the composite of death or myocardial infarction. CONCLUSIONS:Patients receiving DES vs BMS in a clinical practice setting have lower TVR rates, albeit with less absolute benefit than those observed in clinical trials. Patients with multivessel vs single-vessel disease experience a greater reduction in TVR.

Cardiovascular procedures performed in the United States have more than tripled in the last decade, a trend that is expected to continue with the aging of the population, coupled with epidemics of obesity and diabetes mellitus. Helping to drive this increase are new medical devices that address conditions previously treated by medication alone. Many of these novel devices receive expedited reviews before Food and Drug Administration (FDA) approval and are rapidly adopted into clinical practice. However, recent high-profile cases involving potentially dangerous defects in widely used medical devices have increased concerns about the adequacy of premarket trials and postmarket surveillance in establishing the safety of these devices. In response to these concerns, the American College of Cardiology and the Duke Clinical Research Institute sponsored a 'think tank' of experts representing the industry, regulatory authorities, academic medicine, and professional societies to examine these concerns and propose possible solutions. This group examined case studies including drug-eluting stents and implantable cardioverter-defibrillators. Challenges inherent in the current system, including the difficulty of establishing accurate event rates for medical devices and potential disincentives for the industry to conduct comprehensive monitoring, were discussed. Possible solutions to these problems included improving and enforcing current regulations, considering creative study design strategies that link pre- and postmarket data, declaring postmarket surveillance a public health issue, creating financial incentives for participation in postmarketing studies, using more relevant animal models, encouraging postmortem device retrieval, and aligning professional societies with the FDA to evaluate breakthrough technologies and communicate findings to patients and clinicians