Faculty Bibliography

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

BACKGROUND:Guidelines for the management of high-risk non ST-segment elevation acute coronary syndrome (NSTE ACS) recommend antithrombotic and antiplatelet therapy combined with an early invasive strategy. While this strategy reduces ischemic complications, it places patients at risk for bleeding complications. OBJECTIVE:We sought to provide a narrative review of the risk factors for bleeding, risks associated with bleeding and strategies to prevent bleeding complications. METHODS:A comprehensive literature review was performed to identify relevant evidence. RESULTS/CONCLUSIONS/CONCLUSIONS:Bleeding complications in NSTE ACS are associated with adverse events and higher mortality. Prevention of bleeding complications can be achieved through judicious dosing of medications, the use of antithrombotic agents associated with a lower bleeding risk and use of the radial artery approach in patients requiring coronary intervention. Future work should focus on delineating the mechanisms underlying the bleeding-mortality relationship and developing a better understanding of the tradeoff between efficacy and safety.

OBJECTIVES/OBJECTIVE:Our goal was to compare trends in the prevalence and outcomes of the radial and femoral approaches to percutaneous coronary intervention (PCI) in contemporary clinical practice. BACKGROUND:There are few current data on the use and outcomes of the radial approach to PCI (r-PCI) in clinical practice. METHODS:Data from 593,094 procedures in the National Cardiovascular Data Registry (606 sites; 2004 to 2007) were analyzed to evaluate trends in use and outcomes of r-PCI. Logistic regression was used to evaluate the adjusted association between r-PCI and procedural success, bleeding complications, and vascular complications. Outcomes in elderly patients, women, and patients with acute coronary syndrome were specifically examined. RESULTS:Although the proportion of r-PCI procedures has recently increased, it only accounts for 1.32% of total procedures (n = 7,804). Compared with the femoral approach, the use of r-PCI was associated with a similar rate of procedural success (adjusted odds ratio: 1.02 [95% confidence interval: 0.93 to 1.12]) but a significantly lower risk for bleeding complications (odds ratio: 0.42 [95% confidence interval: 0.31 to 0.56]) after multivariable adjustment. The reduction in bleeding complications was more pronounced among patients <75 years old, women, and patients undergoing PCI for acute coronary syndrome. CONCLUSIONS:The use of r-PCI is rare in contemporary clinical practice, but it is associated with a rate of procedural success similar to the femoral approach and with lower rates of bleeding and vascular complications, even among high-risk groups. These results suggest that wider adoption of r-PCI in clinical practice may improve the safety of PCI.

OBJECTIVES/OBJECTIVE:To describe the association between transfusion and outcomes as a function of nadir hematocrit (HCT) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND:The adverse outcomes associated with transfusion in NSTE ACS is uncertain and may vary by nadir HCT of the transfused. METHODS:Using data from 44242 patients with NSTE ACS in 400 US hospitals in the CRUSADE initiative (January 2004-December 2005), we describe blood transfusion as a function of nadir HCT and associated outcomes across nadir HCT groups (<or=24%, 24.1%-27%, 27.1%-30%, >30%). We further explore patient and process variation across hospital quartiles defined by transfusion use. RESULTS:Overall, 22.2% of patients with NSTE ACS are anemic and 10.4% receive a blood transfusion during their care. Likelihood of transfusion rose from 1% when nadir HCT was >30% to 70% when nadir HCT was <or=24%. The threshold for transfusion is a median nadir HCT of 25.7% (interquartile range 23.8%-27.5%). Although nadir HCT of transfused remains constant across quartiles of transfusion use, occurrence of bleeding increases. Inhospital mortality is higher in lower nadir HCT groups. In those with a nadir HCT of <or=24%, transfusion tended to have a beneficial impact on mortality (HCT <or=24% adjusted odds ratio [OR] 0.68 [0.45-1.02]). In the median range where transfusion occurs, transfusion had a neutral impact on mortality (HCT 24%-27% adjusted OR 1.01 [0.79-1.30]). Although rare, those transfused with nadir HCT of 27% to 30% (adjusted OR 1.18 [0.92-1.50]) or HCT of >30% (adjusted OR 3.47 [2.30-5.23]) had higher mortality. CONCLUSION/CONCLUSIONS:Anemia and transfusion are common in the care of NSTE ACS. The observed association between transfusion and adverse outcomes is neutral in the nadir HCT range where transfusions are most often given and trends strongly to benefit when nadir HCT is <or=24%. Although reassuring, randomized trials are needed to confirm the safety of transfusion in NSTE ACS. In the meantime, avoiding the need for transfusion is the best approach.