Faculty Bibliography

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.

Coronary artery plaque rupture results in platelet adhesion and activation, the release of adenosine diphosphate (ADP), thromboxane A(2), and the generation of thrombin. These factors propagate further platelet activation through a positive feedback mechanism, resulting in the formation of a platelet plug. The treatment of patients with ACS is centered upon the prompt initiation of both antiplatelet and anticoagulant agents. The widespread use of antiplatelet and anticoagulant agents has resulted in a significant reduction in morbidity and mortality but has also increased the risk for bleeding complications. Female gender, advanced age, low body mass index (BMI), low creatinine clearance, and the use of percutaneous coronary intervention have been consistently shown to be risk factors for bleeding. While bleeding was thought to be a necessary side effect and of little clinical significance in the past, it is now clear that bleeding is an independent predictor of adverse ischemic events and mortality. The mechanisms underlying this relationship are not yet fully elucidated and are likely multifactorial (direct effects of bleeding, increased incidence of blood transfusions, less use of antiplatelet agents in both the short and long term). Current treatment guidelines for the use of antithrombotic therapy recommend utilization of evidence-based therapies using clinical strategies shown to minimize the risk of bleeding should when possible. Novel therapies that minimize bleeding risk while providing protection against thrombotic events are needed and may improve outcomes among patients with ACS. Multiple platelet activation pathways and the coagulation cascade regulate hemostasis and thrombosis. Current antiplatelet and anticoagulant therapies for acute coronary syndromes (ACS) act on distinct sites in the pathways for platelet activation and coagulation. While these therapies are effective in reducing the morbidity and mortality associated with ACS, they are associated with a clinically significant increase in the risk of bleeding events. Novel therapies that minimize bleeding risk while providing protection against thrombotic events may improve outcomes in patients with ACS.

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.

BACKGROUND:Although bivalirudin compared with unfractionated heparin with glycoprotein IIb/IIIa inhibitors reduces bleeding and hospitalization costs in patients undergoing percutaneous coronary intervention (PCI), little is known about the economic impact of bivalirudin versus heparin alone and at what threshold of procedural bleeding risk bivalirudin would be considered cost-effective. METHODS AND RESULTS/RESULTS:A validated model was used to predict risk of major bleeding for 81,628 National Cardiovascular Data Registry (NCDR) CathPCI Registry patients from 2004 to 2006 who received unfractionated heparin only. Costs were derived from multiple sources including wholesale acquisition costs (for drugs) and single-center data (for PCI-related complications). Based on ISAR-REACT 3, we assumed that bivalirudin would reduce the risk of major bleeding by 33% compared with unfractionated heparin alone. A Markov model was used to estimate lost life expectancy associated with a major bleed. Major bleeding was predicted to occur in 2.2% of patients. Bivalirudin for all patients was estimated to increase costs by $571 per patient, yielding cost-effectiveness ratios of $287,473 per bleeding event averted and $1,173,360 per quality-adjusted life-year gained. Bivalirudin was cost saving for patients with a predicted bleeding risk >20% (0.16% of CathPCI population). At willingness-to-pay thresholds of $50K and $100K per quality-adjusted life-year gained, bivalirudin was cost-effective for patients with a bleeding risk > or = 8% (2.5% patients) and > or = 5% (7.9% patients), respectively. CONCLUSIONS:This decision-analytic modeling study demonstrates that for patients undergoing PCI, substitution of bivalirudin for unfractionated heparin monotherapy is projected to increase costs for virtually all patients and would be considered cost-effective for only a minority of patients with a high bleeding risk. From a policy standpoint, studies such as this, aimed at identifying the appropriate risk threshold for initiating treatment, may help in the development of informed guidelines for the use of expensive therapies.

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.

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.

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.

Despite current dual-antiplatelet therapy with aspirin and clopidogrel, adverse clinical events continue to occur during and after percutaneous coronary intervention (PCI). The failure of clopidogrel to provide optimal protection may be related to delayed onset of action, interpatient variability in its effect, and an insufficient level of platelet inhibition. Furthermore, the irreversible binding of clopidogrel to the P2Y(12) receptor for the life span of the platelet is associated with increased bleeding risk especially during urgent or emergency surgery. Novel antiplatelet agents are required to improve management of patients undergoing PCI. Elinogrel is a potent, direct-acting (ie, non-prodrug), selective, competitive, and reversible P2Y(12) inhibitor available in both intravenous and oral formulations. The INNOVATE-PCI study is a phase 2 randomized, double-blind, clopidogrel-controlled trial to evaluate the safety, tolerability, and preliminary efficacy of this novel antiplatelet agent in patients undergoing nonurgent PCI.