Faculty Bibliography

CONTEXT/BACKGROUND:Bleeding complications with percutaneous coronary intervention (PCI) are associated with adverse patient outcomes. The association between the use of bleeding avoidance strategies and post-PCI bleeding as a function of a patient's preprocedural risk of bleeding is unknown. OBJECTIVE:To describe the use of 2 bleeding avoidance strategies, vascular closure devices and bivalirudin, and associated post-PCI bleeding rates in a nationally representative PCI population. DESIGN, SETTING, AND PATIENTS/METHODS:Analysis of data from 1,522,935 patients undergoing PCI procedures performed at 955 US hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry from January 1, 2004, through September 30, 2008. MAIN OUTCOME MEASURE/METHODS:Periprocedural bleeding. RESULTS:Bleeding occurred in 30,654 patients (2%). Manual compression, vascular closure devices, bivalirudin, or vascular closure devices plus bivalirudin were used in 35%, 24%, 23%, and 18% of patients, respectively. Bleeding events were reported in 2.8% of patients who received manual compression, compared with 2.1%, 1.6%, and 0.9% of patients receiving vascular closure devices, bivalirudin, and both strategies, respectively (P < .001). Bleeding rates differed by preprocedural risk assessed with the NCDR bleeding risk model (low risk, 0.72%; intermediate risk, 1.73%; high risk, 4.69%). In high-risk patients, use of both strategies was associated with lower bleeding rates (manual compression, 6.1%; vascular closure devices, 4.6%; bivalirudin, 3.8%; vascular closure devices plus bivalirudin, 2.3%; P < .001). This association persisted following adjustment using a propensity-matched and site-controlled model. Use of both strategies was used least often in high-risk patients (14.4% vs 21.0% in low-risk patients, P < .001). CONCLUSIONS:In a large national PCI registry, vascular closure devices and bivalirudin were associated with significantly lower bleeding rates, particularly among patients at greatest risk for bleeding. However, these strategies were less often used among higher-risk patients.

Thrombocytopenia is associated with increased patient risk. However, the costs of this complication are not well defined. This study assessed the impact of thrombocytopenia on in-hospital costs using results from CATCH, an observational study that examined 1988 consecutive patients receiving prolonged heparin therapy (> or =96 h). Thrombocytopenia was defined as: (group 1) an absolute reduction in platelet count to <150 x 10(9)/L; (group 2) a relative reduction in platelet count of >50% from admission levels; or (group 3) both criteria. We found that the development of thrombocytopenia was associated with significantly higher total in-hospital costs for all groups: (group 1) (difference, $8,222; 95% CI, $5,020-$11,425; P<.001); (group 2) (difference, $15,429; 95% CI, $7,472-$23,385; P<.001); and (group 3) (difference, $27,077; 95% CI, $22,901-$31,252; P<.001). However, in our adjusted model, longer lengths-of-stay and greater use of blood transfusions accounted for most incremental in-hospital cost differences.

Antithrombotic and antiplatelet drugs and percutaneous interventions have decreased the ischemic outcomes of non-ST-elevation acute coronary syndromes, but they pose risks of bleeding. The authors review the scope of the problem and ways to prevent and manage bleeding in this situation.

AIMS/OBJECTIVE:We studied the clinical and economic impact of bivalirudin in clinical practice. METHODS AND RESULTS/RESULTS:Consecutive patients undergoing PCI via the common femoral artery for stable, unstable, or atypical angina, silent ischaemia, or non-ST-elevation myocardial infarction indications during 2007-2008 were prospectively studied. In-hospital bleeding events were systematically assessed and classified as either major or minor. Use of bivalirudin, vascular closure devices, heparin and/or glycoprotein (GP) IIb/IIIa inhibitor was at the operator's discretion. Among 1,364 patients, 503 received bivalirudin and 861 received usual care consisting of either heparin monotherapy (n=687) or heparin+GP IIb/IIIa (n=174). Any post-PCI bleeding occurred in 356 (26.1%) patients, including 32 (2.3%) major and 324 (23.8%) minor events. Compared with usual care, bivalirudin was associated with reduced bleeding before adjustment (any: 17.3% vs. 31.2%, P<0.001; major: 1.2% vs. 3.0%, P=0.03; minor: 16.1% vs. 28.2%, P<0.01) and after propensity-matching (OR 0.46, 95% CI 0.34-0.63, P<0.001). Use of vascular closure devices was associated with an increase in any bleeding (32.2% vs. 17.7%, P<0.001), primarily due to an increase in minor bleeding (30.8% vs. 14.1%, P<0.001) while there was a significant decrease in major bleeding (1.4% vs. 3.7%, P=0.007). Bivalirudin was associated with total hospitalisation costs that were lower than usual care (mean cost savings, $463/patient; 95% CI 1,594 less to 621 more). CONCLUSIONS:In this prospective PCI cohort, bivalirudin was associated with reduced major and minor bleeding without a significant increase in hospital costs compared with other anticoagulation regimens. Closure device use was associated with decreased major but increased minor bleeding.

Periprocedural bleeding complications after percutaneous coronary intervention (PCI) are associated with increased short- and long-term morbidity and mortality. Although clinical trials have primarily assessed pharmacological strategies for reducing bleeding risk, there is a mounting body of evidence suggesting that adoption of a transradial rather than a transfemoral approach to PCI may permit greater reductions in bleeding risk than have been achieved with pharmacological strategies alone. However, despite a long history of use, a lack of widespread uptake by physicians coupled with the technological limitations of available devices has in the past confined transradial PCI to the status of a niche procedure, and many operators lack experience in this technique. In this review, we examine the history of the transradial approach to PCI and discuss some of the circumstances that have hitherto limited its appeal. We then review the current state of the peer-reviewed literature supporting its use and summarize the unresolved issues affecting broader application of this technique, including lack of operator familiarity and an insufficient evidence base for guiding practice. Finally, we describe potential directions for future investigation in the transradial realm.

OBJECTIVES/OBJECTIVE:We sought to create contemporary models for predicting mortality risk following percutaneous coronary intervention (PCI). BACKGROUND:There is a need to identify PCI risk factors and accurately quantify procedural risks to facilitate comparative effectiveness research, provider comparisons, and informed patient decision making. METHODS:Data from 181,775 procedures performed from January 2004 to March 2006 were used to develop risk models based on pre-procedural and/or angiographic factors using logistic regression. These models were independently evaluated in 2 validation cohorts: contemporary (n = 121,183, January 2004 to March 2006) and prospective (n = 285,440, March 2006 to March 2007). RESULTS:Overall, PCI in-hospital mortality was 1.27%, ranging from 0.65% in elective PCI to 4.81% in ST-segment elevation myocardial infarction patients. Multiple pre-procedural clinical factors were significantly associated with in-hospital mortality. Angiographic variables provided only modest incremental information to pre-procedural risk assessments. The overall National Cardiovascular Data Registry (NCDR) model, as well as a simplified NCDR risk score (based on 8 key pre-procedure factors), had excellent discrimination (c-index: 0.93 and 0.91, respectively). Discrimination and calibration of both risk tools were retained among specific patient subgroups, in the validation samples, and when used to estimate 30-day mortality rates among Medicare patients. CONCLUSIONS:Risks for early mortality following PCI can be accurately predicted in contemporary practice. Incorporation of such risk tools should facilitate research, clinical decisions, and policy applications.

BACKGROUND:Factor Xa and factor IIa (thrombin) play roles in thrombotic complications after percutaneous coronary intervention. M118 is a novel low-molecular-weight heparin that has been rationally designed to capture the desired attributes of unfractionated heparin (UFH) and low-molecular-weight heparin: Potent activity against factor Xa and IIa, predictable pharmacokinetics after both intravenous and subcutaneous administration, ability to be monitored by use of point-of-care coagulation assays, and reversibility with protamine sulfate. We performed a phase 2 randomized trial to evaluate the safety and feasibility of M118 in the setting of elective percutaneous coronary intervention. METHODS AND RESULTS/RESULTS:Overall, 503 patients undergoing elective percutaneous coronary intervention at 43 centers in the United States and Canada were randomized in an open-label fashion to 1 of 4 arms: UFH 70 U/kg, M118 50 IU/kg IV, M118 75 IU/kg IV, or M118 100 IU/kg IV. The primary outcome was the composite of death, myocardial infarction, repeat revascularization, stroke, thrombocytopenia, catheter thrombus, bailout use of glycoprotein IIb/IIIa inhibitor, or any bleeding through 30 days. The primary end point occurred in 31.1% of patients randomized to UFH and in 22.7%, 28.3%, and 30.1% of patients randomized to M118 50, 75, and 100 IU/kg, respectively. The primary analysis comparing the rates of the primary end points between the pooled M118 groups versus UFH demonstrated that M118 was noninferior to UFH at preventing percutaneous coronary intervention-related complications (28.4% pooled M118 arms versus 31.1% UFH). The adverse event profiles of M118 and UFH were comparable. CONCLUSIONS:This phase 2 randomized trial demonstrates that M118 is well tolerated and feasible to use as an anticoagulant in patients undergoing elective percutaneous coronary intervention and forms the basis for further investigation of this agent in ischemic heart disease. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543400.

BACKGROUND:Previous data on bleeding after percutaneous coronary intervention (PCI) have been obtained primarily from randomized trials that focused on in-hospital bleeding. The incidence of late bleeding after PCI, its independent predictors, and its prognostic importance in clinical practice has not been fully addressed. METHODS AND RESULTS/RESULTS:We evaluated 22 798 patients aged >65 years who underwent PCI from December 1, 2003, to March 31, 2007, in Ontario, Canada. Cox proportional hazard models were used to determine factors associated with late bleeding, which was defined as hospitalization for bleeding after discharge from the index PCI, and to estimate risk of death or myocardial infarction associated with late bleeding. We found that 2.5% of patients were hospitalized for bleeding in the year after PCI, with 56% of bleeding episodes due to gastrointestinal bleed. The most significant predictor of late bleeding was warfarin use after PCI (hazard ratio [HR], 3.12). Other significant predictors included age (HR, 1.41 per 10 years), male sex (HR, 1.24), cancer (HR, 1.80), previous bleeding (HR, 2.42), chronic kidney disease (HR, 1.93), and nonsteroidal antiinflammatory drug use (HR, 1.73). After adjusting for baseline covariates, hospitalization for a bleeding episode was associated with a significantly increased 1-year hazard of death or myocardial infarction (HR, 2.39; 95% CI, 1.93 to 2.97) and death (HR, 3.38; 95% CI, 2.60 to 4.40). CONCLUSIONS:Hospitalization for late bleeding after PCI is associated with substantially increased risk of death and myocardial infarction. The use of triple therapy (i.e., aspirin, thienopyridine, and warfarin) is associated with the highest risk of late bleeding.