SCAI expert consensus update on best practices in the cardiac catheterization laboratory: This statement was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Rhythm Society (HRS) in April 2021.

The current document commissioned by the Society for Cardiovascular Angiography and Interventions (SCAI) and endorsed by the American College of Cardiology, the American Heart Association, and Heart Rhythm Society represents a comprehensive update to the 2012 and 2016 consensus documents on patient-centered best practices in the cardiac catheterization laboratory. Comprising updates to staffing and credentialing, as well as evidence-based updates to the pre-, intra-, and post-procedural logistics, clinical standards and patient flow, the document also includes an expanded section on CCL governance, administration, and approach to quality metrics. This update also acknowledges the collaboration with various specialties, including discussion of the heart team approach to management, and working with electrophysiology colleagues in particular. It is hoped that this document will be utilized by hospitals, health systems, as well as regulatory bodies involved in assuring and maintaining quality, safety, efficiency, and cost-effectiveness of patient throughput in this high volume area.

Comprehensive electrocardiogram-to-device time for primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: A report from the American Heart Association mission: Lifeline program.

BACKGROUND: Assessing hospital-related network-level primary percutaneous coronary intervention (PCI) performance for ST-segment elevation myocardial infarction (STEMI) is challenging due to differential time-to-treatment metrics based on location of diagnostic electrocardiogram (ECG) for STEMI. METHODS: STEMI patients undergoing primary PCI at 588 PCI-capable hospitals in AHA Mission: Lifeline (2008-2013) were categorized by initial STEMI identification location: PCI-capable hospitals (Group 1); pre-hospital setting (Group 2); and non-PCI-capable hospitals (Group 3). Patient-specific time-to-treatment categories were converted to minutes ahead of or behind their group-specific mean; average time-to-treatment difference for all patients at a given hospital was termed comprehensive ECG-to-device time. Hospitals were then stratified into tertiles based on their comprehensive ECG-to-device times with negative values below the mean representing shorter (faster) time intervals. RESULTS: Of 117,857 patients, the proportion in Groups 1, 2, and 3 were 42%, 33%, and 25%, respectively. Lower rates of heart failure and cardiac arrest at presentation are noted within patients presenting to high-performing hospitals. Median comprehensive ECG-to-device time was shortest at -9 minutes (25th, 75th percentiles: -13, -6) for the high-performing hospital tertile, 1 minute (-1, 3) for middle-performing, and 11 minutes (7, 16) for low-performing. Unadjusted rates of in-hospital mortality were 2.3%, 2.6%, and 2.7%, respectively, but the adjusted risk of in-hospital mortality was similar across tertiles. CONCLUSIONS: Comprehensive ECG-to-device time provides an integrated hospital-related network-level assessment of reperfusion timing metrics for primary PCI, regardless of the location for STEMI identification; further validation will delineate how this metric can be used to facilitate STEMI care improvements.

The effect of high-risk ST elevation myocardial infarction transfer patients on risk-adjusted in-hospital mortality: A report from the American Heart Association Mission: Lifeline program.

BACKGROUND: Hospital mortality is an important quality measure for acute myocardial infarction care. There is a concern that despite risk adjustment, percutaneous coronary intervention hospitals accepting a greater volume of high-risk ST elevation myocardial infarction (STEMI) transfer patients may have their reported mortality rates adversely affected. METHODS: The STEMI patients in the National Cardiovascular Data RegistryAcute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines from April 2011 to December 2013 were included. High-risk STEMI was defined as having either cardiogenic shock or cardiac arrest on first medical contact. Receiving hospitals were divided into tertiles based on the ratio of high-risk STEMI transfer patients to the total number of STEMI patients treated at each hospital. Using the Action Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines in-hospital mortality risk model, we calculated the difference in risk-standardized in-hospital mortality before and after excluding high-risk STEMI transfers in each tertile. RESULTS: Among 119,680 STEMI patients treated at 539 receiving hospitals, 37,028 (31%) were transfer patients, of whom 4,500 (12%) were highrisk. The proportion of high-risk STEMI transfer patients ranged from 0% to 12% across hospitals. Unadjusted mortality rates in the low-, middle-, and high-tertile hospitals were 6.0%, 6.0%, and 5.9% among all STEMI patients and 6.0%, 5.5%, and 4.6% after excluding high-risk STEMI transfers. However, risk-standardized hospital mortality rates were not significantly changed after excluding high-risk STEMI transfer patients in any of the 3 hospital tertiles (low, -0.04%; middle, -0.05%; and high, 0.03%). CONCLUSIONS: Risk-adjusted in-hospital mortality rates were not adversely affected in STEMI-receiving hospitals who accepted more high-risk STEMI transfer patients when a clinical mortality risk model was used for risk adjustment.

Emergency medical services management of ST-segment elevation myocardial infarction in the United States--a report from the American Heart Association Mission: Lifeline Program.

OBJECTIVE: ST-segment elevation myocardial infarction (STEMI) is a major cause of morbidity and mortality in the United States. Emergency medical services (EMS) agencies play a critical role in its initial identification and treatment. We conducted this study to assess EMS management of STEMI care in the United States. METHODS: A structured questionnaire was administered to leaders of EMS agencies to define the elements of STEMI care related to 4 core measures: (1) electrocardiogram (ECG) capability at the scene, (2) destination protocols, (3) catheterization laboratory activation before hospital arrival, and (4) 12-lead ECG quality review. Geographic areas were grouped into large metropolitan, small metropolitan, micropolitan, and noncore (or rural) by using Urban Influence Codes, with a stratified analysis. RESULTS: Data were included based on responses from 5296 EMS agencies (36% of those in the United States) serving 91% of the US population, with at least 1 valid response from each of the 50 states and the District of Columbia. Approximately 63% of agencies obtained ECGs at the scene using providers trained in ECG acquisition and interpretation. A total of 46% of EMS systems used protocols to determine hospital destination, cardiac catheterization laboratory activation, and communications with the receiving hospital. More than 75% of EMS systems used their own agency funds to purchase equipment, train personnel, and provide administrative oversight. A total of 49% of agencies have quality review programs in place. In general, EMS systems covering higher population densities had easier access to resources needed to maintain STEMI systems of care. Emergency medical services systems that have adopted all 4 core elements cover 14% of the US population. CONCLUSIONS: There are large differences in EMS systems of STEMI care in the United States. Most EMS agencies have implemented at least 1 of the 4 core elements of STEMI care, with many having implemented multiple elements.

Safety and efficacy of cangrelor, an intravenous, short-acting platelet inhibitor in patients requiring coronary artery bypass surgery.

OBJECTIVE: Oral P2Y12 platelet receptor inhibitors are a cornerstone of reducing complications in patients with acute coronary syndromes or coronary stents. Guidelines advocate discontinuing treatment with P2Y12 platelet receptor inhibitors before surgery. Cangrelor, a short-acting, reversible, intravenously administered P2Y12 platelet inhibitor is effective in achieving appropriate platelet inhibition in patients who are awaiting coronary artery bypass grafting (CABG) and require P2Y12 inhibition. The objective of this study was to assess the effects of preoperative cangrelor on the incidence of perioperative complications, which are currently unknown. METHODS: Patients (n = 210) requiring preoperative clinical administration of thienopyridine therapy were randomized in a multicenter, double-blinded study to receive cangrelor or placebo while awaiting CABG after discontinuation of the thienopyridine. Optimal platelet reactivity, which was defined as <240 P2Y12 platelet reaction units, was measured with serial point-of-care testing (VerifyNow). Pre- and postoperative outcomes, bleeding values, and transfusion rates were compared. To quantify potential risk factors for bleeding, we developed a multivariate logistic model. RESULTS: The differences between the groups in bleeding and perioperative transfusion rates were not significantly different. The rate of CABG-related bleeding was 11.8% (12/102) in cangrelor-treated patients and 10.4% (10/96) in the placebo group (P = .763). Transfusion rates for the groups were similar. Serious postoperative adverse events for the cangrelor and placebo groups were 7.8% (8/102) and 5.2% (5/96), respectively (P = .454). CONCLUSIONS: Compared with placebo, bridging patients with cangrelor prior to CABG effectively maintains platelet inhibition without increasing post-CABG complications, including bleeding and the need for transfusions. These data suggest cangrelor treatment is a potential strategy for bridging patients requiring P2Y12 receptor inhibition while they await surgery.

Impact of Computer-Interpreted ECGs on the Accuracy of Healthcare Professionals.

The interpretation of electrocardiograms (ECGs) involves a dynamic interplay between computerized ECG interpretation (CEI) software and human overread. However, the impact of computer ECG interpretation on the performance of healthcare professionals remains largely unexplored. The aim of this study was to evaluate the interpretation proficiency of various medical professional groups, with and without access to the CEI report. Healthcare professionals from diverse disciplines, training levels, and countries sequentially interpreted 60 standard 12-lead ECGs, demonstrating both urgent and nonurgent findings. The interpretation process consisted of 2 phases. In the first phase, participants interpreted 30 ECGs with clinical statements. In the second phase, the same 30 ECGs and clinical statements were randomized and accompanied by a CEI report. Diagnostic performance was evaluated based on interpretation accuracy, time per ECG (in seconds [s]), and self-reported confidence (rated 0 [not confident], 1 [somewhat confident], or 2 [confident]). A total of 892 participants from various medical professional groups participated in the study. This cohort included 44 (4.9%) primary care physicians, 123 (13.8%) cardiology fellows-in-training, 259 (29.0%) resident physicians, 137 (15.4%) medical students, 56 (6.3%) advanced practice providers, 82 (9.2%) nurses, and 191 (21.4%) allied health professionals. The inclusion of the CEI was associated with a significant improvement in interpretation accuracy by 15.1% (95% confidence interval, 14.3-16.0; P < 0.001), decrease in interpretation time by 52 s (-56 to -48; P < 0.001), and increase in confidence by 0.06 (0.03-0.09; P = 0.003). Improvement in interpretation accuracy was seen across all professional subgroups, including primary care physicians by 12.9% (9.4-16.3; P = 0.003), cardiology fellows-in-training by 10.9% (9.1-12.7; P < 0.001), resident physicians by 14.4% (13.0-15.8; P < 0.001), medical students by 19.9% (16.8-23.0; P < 0.001), advanced practice providers by 17.1% (13.3-21.0; P < 0.001), nurses by 16.2% (13.4-18.9; P < 0.001), allied health professionals by 15% (13.4-16.6; P < 0.001), physicians by 13.2% (12.2-14.3; P < 0.001), and nonphysicians by 15.6% (14.3-17.0; P < 0.001).CEI integration improves ECG interpretation accuracy, efficiency, and confidence among healthcare professionals.

Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial.

BACKGROUND: In the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial, 6 months of high-dose clopidogrel did not reduce cardiovascular events compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity (OTR) after percutaneous coronary intervention, defined as OTR ≥230 P2Y12 reaction units according to the VerifyNow P2Y12 platelet function test. The aim of this analysis was to examine the relationship between outcomes and OTR over the course of the trial. METHODS AND RESULTS: OTR was measured at 12 to 24 hours and 30±7 days after percutaneous coronary intervention. Cox proportional hazards models with OTR as a time-varying covariate were used to determine the association between OTR and the primary end point of cardiovascular death, myocardial infarction, and stent thrombosis. Of the 2800 enrolled patients, 2796 (99.98%) had evaluable platelet function data. OTR <208 P2Y12 reaction units was significantly associated with a lower risk of the primary end point at 60 days (hazard ratio, 0.18; 95% confidence interval, 0.04 to 0.79; P=0.02) and at 6 months (hazard ratio, 0.43; 95% confidence interval, 0.23 to 0.82; P=0.01). After adjustment for other significant predictors of outcome, OTR <208 P2Y12 reaction units remained independently associated with the primary end point at 60 days (hazard ratio, 0.23; 95% confidence interval, 0.05 to 0.98; P=0.047) and tended to be associated at 6 months (adjusted hazard ratio, 0.54; 95% confidence interval, 0.28 to 1.04; P=0.065). CONCLUSIONS: In the GRAVITAS trial, achievement of on-clopidogrel reactivity <208 P2Y12 reaction units at 12 to 24 hours after percutaneous coronary intervention or during follow-up was associated with a lower risk for cardiovascular events. The efficacy of an individualized strategy to target a level of OTR below this threshold merits investigation. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00645918.

Intravenous platelet blockade with cangrelor during PCI.

BACKGROUND: Intravenous cangrelor, a rapid-acting, reversible adenosine diphosphate (ADP) receptor antagonist, might reduce ischemic events during percutaneous coronary intervention (PCI). METHODS: In this double-blind, placebo-controlled study, we randomly assigned 5362 patients who had not been treated with clopidogrel to receive either cangrelor or placebo at the time of PCI, followed by 600 mg of clopidogrel. The primary end point was a composite of death, myocardial infarction, or ischemia-driven revascularization at 48 hours. Enrollment was stopped when an interim analysis concluded that the trial would be unlikely to show superiority for the primary end point. RESULTS: The primary end point occurred in 185 of 2654 patients receiving cangrelor (7.0%) and in 210 of 2641 patients receiving placebo (8.0%) (odds ratio in the cangrelor group, 0.87; 95% confidence interval [CI], 0.71 to 1.07; P=0.17) (modified intention-to-treat population adjusted for missing data). In the cangrelor group, as compared with the placebo group, two prespecified secondary end points were significantly reduced at 48 hours: the rate of stent thrombosis, from 0.6% to 0.2% (odds ratio, 0.31; 95% CI, 0.11 to 0.85; P=0.02), and the rate of death from any cause, from 0.7% to 0.2% (odds ratio, 0.33; 95% CI, 0.13 to 0.83; P=0.02). There was no significant difference in the rate of blood transfusion (1.0% in the cangrelor group and 0.6% in the placebo group, P=0.13), though major bleeding on one scale was increased in the cangrelor group, from 3.5% to 5.5% (P<0.001), because of more groin hematomas. CONCLUSIONS: The use of periprocedural cangrelor during PCI was not superior to placebo in reducing the primary end point. The prespecified secondary end points of stent thrombosis and death were lower in the cangrelor group, with no significant increase in the rate of transfusion. Further study of intravenous ADP blockade with cangrelor may be warranted. (ClinicalTrials.gov number, NCT00385138.)

Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial.

CONTEXT: Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding. OBJECTIVE: To evaluate the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery. DESIGN, SETTING, AND PATIENTS: Prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery. MAIN OUTCOME MEASURES: The primary efficacy end point was platelet reactivity (measured in P2Y(12) reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery-related bleeding. RESULTS: The dose of cangrelor determined in 10 patients in the open-label stage was 0.75 µg/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery-related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor. CONCLUSIONS: Among patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00767507.

Incidence and clinical consequences of acquired thrombocytopenia after antithrombotic therapies in patients with acute coronary syndromes: results from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.

BACKGROUND: The aim of the study was to investigate the incidence and clinical consequences of acquired thrombocytopenia in patients with acute coronary syndromes (ACS) in the ACUITY trial. METHODS: We examined 10,836 patients with ACS randomized to receive heparin plus glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin plus GP IIb/IIIa inhibitor, or bivalirudin monotherapy. RESULTS: Acquired thrombocytopenia developed in 740 (6.8%) patients; mild (100,000-150,000 platelets/mm³), moderate (50,000-100,000 platelets/mm³), and severe (< 50,000 platelets/mm³) developed in 656 (6%), 51 (0.5%), and 33 (0.3%) patients, respectively. Patients with acquired thrombocytopenia, compared with those without, were more likely to develop major bleeding (14% vs 4.3%, P < .0001) at 30 days and had higher rates of mortality (6.5% vs 3.4%, P < .0001) at 1 year. By multivariate analysis, acquired thrombocytopenia was an independent predictor of major bleeding at 30 days (hazard ratio [HR] 1.68, 95% CI 1.04-2.72, P = .03). Moderate and severe acquired thrombocytopenia were predictors of mortality at 1 year (HR 2.89, 95% CI 0.92-9.06, P = .06, and HR 3.41, 95% CI 1.09-10.68, P = .03, respectively). Compared to heparin plus GP IIb/IIIa inhibitor, bivalirudin monotherapy was associated with less declines in platelet count by >25% (7.6% vs 5.6%, P = .0009) and >50% (1.4% vs 0.7%, P = .004) from baseline. CONCLUSIONS: Acquired thrombocytopenia occurs in approximately 1 in 14 patients with ACS treated with antithrombin and antiplatelet medications and is strongly associated with hemorrhagic and ischemic complications. Compared to an anticoagulant regimen including a GP IIb/IIIa inhibitor, administration of bivalirudin monotherapy appears to be associated with less frequent declines in platelet count.

Impact of baseline thrombocytopenia on the early and late outcomes after ST-elevation myocardial infarction treated with primary angioplasty: analysis from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.

BACKGROUND: Thrombocytopenia (TP) is a common abnormality in patients presenting with acute coronary syndrome. Whether baseline TP has any influence on the outcome of patients treated with primary angioplasty for acute myocardial infarction is unknown. METHODS: We sought to detect the impact of baseline TP on the early and late outcomes of patients with ST-elevation myocardial infarction in the HORIZONS-AMI trial that included a protocol of immediate angiography and primary percutaneous coronary intervention. RESULTS: Baseline TP was found in 4.2% of patients and was associated with a higher incidence of cardiovascular mortality, major bleeding, and major cardiovascular events at short- and long-term follow-up. The 30-day rates of death, major bleeding, major cardiac events, and major cardiac events plus major bleeding were 6.2%, 11.9%, 9.6%, and 18.5% in the TP group, respectively, compared with 2.1%, 7%, 5.2%, and 10.8% in those without TP (P < .05 for all). Similarly, event rates at 2 years were 11.3%, 12.7%, 24.7%, and 30.8% compared with 5.1%, 7.9%, 18.5%, and 23.3% (P < .05). By multivariate analysis, baseline TP was an independent predictor of 30-day net adverse clinical events but not of any 2-year events. CONCLUSIONS: We found that baseline TP in patients with ST-elevation myocardial infarction undergoing routine angiography and primary percutaneous coronary intervention is strongly associated with early adverse events and is a maker of late events, related to both ischemia and bleeding.

Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial.

CONTEXT: High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined. OBJECTIVE: To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. INTERVENTIONS: High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. MAIN OUTCOME MEASURES: The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days. RESULTS: At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001). CONCLUSIONS: Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00645918.

Novel antiplatelet therapy.

Antiplatelet therapy is a cornerstone of the management of patients with acute coronary syndromes or for those undergoing percutaneous coronary intervention. As the intricacies of platelet biology and mechanisms of thrombus formation are revealed, novel antiplatelet therapies have emerged. Bleeding risk, however, has grown in concert with more potent platelet inhibition. This article reviews platelet biology and receptors to provide a foundation for understanding of antiplatelelet therapy. It also highlights recent advances in antiplatelet therapy, with a focus on mechanisms of action, pharmacodynamic data, and the balance of thrombotic versus bleeding outcomes.

Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial.

AIMS: To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied. METHODS AND RESULTS: A multivariable Cox regression model was developed relating 13 independent baseline predictors to 1-year mortality for 13 819 patients with moderate and high-risk ACS enrolled in the Acute Catheterization and Urgent Intervention Triage strategy trial. After adjustment for baseline predictors, Cox models with major bleeding and recurrent MI as time-updated covariates estimated the effect of these events on mortality hazard over time. Within 30 days of randomization, 705 patients (5.1%) had an MI, 645 (4.7%) had a major bleed; 524 (3.8%) died within a year. The occurrence of an MI was associated with a hazard ratio of 3.1 compared with patients not yet having an MI, after adjustment for baseline predictors. However, MI within 30 days markedly increased the mortality risk for the first 2 days after the event (adjusted hazard ratio of 17.6), but this risk declined rapidly post-infarct (hazard ratio of 1.4 beyond 1 month after the MI event). In contrast, major bleeding had a prolonged association with mortality risk (hazard ratio of 3.5) which remained fairly steady over time throughout 1 year. CONCLUSION: After accounting for baseline predictors of mortality, major bleeds and MI have similar overall strength of association with mortality in the first year after ACS. MI is correlated with a dramatic increase in short-term risk, whereas major bleeding correlates with a more prolonged mortality risk.

Standardized reporting of bleeding complications for clinical investigations in acute coronary syndromes: a proposal from the academic bleeding consensus (ABC) multidisciplinary working group.

BACKGROUND: Clinical trials of antithrombotic agents for the treatment of ACS routinely assess bleeding as a safety endpoint, but variation in bleeding definitions makes comparison of the relative safety of these agents difficult. METHODS: The ABC Multidisciplinary Working Group, an informal working group comprising clinical researchers and representatives from the US Food and Drug Administration, the National Institutes of Health, and the pharmaceutical industry, sought to develop a consensus approach to measuring the incidence and severity of bleeding complications during clinical trials of acute coronary syndromes (ACS). A meeting of the ABC was convened in April 2008 in Washington, DC, with the goal of developing a consensus approach to measuring the incidence and severity of hemorrhagic complications during clinical trials of ACS. Relevant literature on bleeding was reviewed through a series of short lectures and intensive group discussion. RESULTS: Using existing evidence on bleeding and outcomes as well as clinical judgment, criteria for the assessment of bleeding were developed through expert consensus. This consensus statement divides bleeding-related data elements into three categories: essential, recommended, and optional. CONCLUSIONS: The ABC Group recommendations for collection and reporting of bleeding complications provide a framework for consistency in the collection of information on hemorrhagic complications in trials of ACS. Widespread adoption of the statement recommendations will facilitate understanding of the mechanisms of adverse outcomes after bleeding and comparisons of the relative safety of antithrombotic agents, as well as the interpretation of safety results from future studies.

Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial.

BACKGROUND: The aim of this study was to assess anticoagulation with the direct thrombin inhibitor bivalirudin during percutaneous coronary intervention in individuals with moderate and high-risk acute coronary syndromes. METHODS: 13,819 individuals in the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial were prospectively randomly assigned to receive heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitors, bivalirudin plus glycoprotein IIb/IIIa inhibitors, or bivalirudin alone. Of these individuals, 7789 underwent percutaneous coronary intervention after angiography. The effect of the three regimens on the primary 30-day endpoints of composite ischaemia (death, myocardial infarction, or unplanned revascularisation for ischaemia), major bleeding, and net clinical outcomes (composite ischaemia or major bleeding) was assessed in this subgroup. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, with the number NCT00093158. FINDINGS: Of the individuals who underwent percutaneous coronary intervention, 2561 received heparin plus glycoprotein IIb/IIIa inhibitors, 2609 received bivalirudin plus glycoprotein IIb/IIIa inhibitors, and 2619 received bivalirudin alone. 26 (0.3%) individuals dropped out or were lost to follow-up. There was no significant difference in the proportion of individuals with composite ischaemia, major bleeding, or net clinical outcomes at 30 days between those who received bivalirudin plus glycoprotein IIb/IIIa inhibitors and those who received heparin plus glycoprotein IIb/IIIa inhibitors (composite ischaemia: 243 [9%] patients vs 210 [8%] patients, p=0.16; major bleeding: 196 [8%] patients vs 174 [7%] patients, p=0.32; net clinical outcomes: 389 [15%] patients vs 341 [13%] patients, p=0.1). Rates of composite ischaemia were much the same in those who received bivalirudin alone and those who received heparin plus glycoprotein IIb/IIIa inhibitors (230 [9%] patients vs 210 [8%] patients, p=0.45); however, there were significantly fewer individuals who experienced major bleeding among those who received bivalirudin alone than among those who received heparin plus glycoprotein IIb/IIIa inhibitors (92 [4%] patients vs 174 [7%] patients, p<0.0001, relative risk 0.52, 95% CI 0.40-0.66), resulting in a trend towards better 30-day net clinical outcomes (303 [12%] patients vs 341 [13%] patients, p=0.057; 0.87, 0.75-1.00). INTERPRETATION: Substitution of unfractionated heparin or enoxaparin with bivalirudin results in comparable clinical outcomes in patients with moderate and high-risk acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors in whom percutaneous coronary intervention is done. Anticoagulation with bivalirudin alone suppresses adverse ischaemic events to a similar extent as does heparin plus glycoprotein IIb/IIIa inhibitors, while significantly lowering the risk of major haemorrhagic complications.

Treatment strategies in non-ST-elevation acute coronary syndromes in patients undergoing percutaneous coronary intervention: an evidence-based review of clinical trial results and treatment guidelines: report on a roundtable discussion.

With the availability of new data and the recent release of new European and US guidelines, contemporary care paradigms for the treatment of patients with non-ST-elevation acute coronary syndromes (NSTE ACS), including those undergoing percutaneous coronary intervention, are likely to undergo substantial changes. In recognition of this shifting landscape as well as the impact of new guidelines on care models for the treatment of patients with NSTE ACS, a roundtable was convened on October 25, 2007, to discuss the implications of these changes. The purpose of this review is to summarize the presentations and subsequent discussions from the roundtable, which examined the guidelines and evidence from a variety of perspectives, and to explore the best ways to incorporate new treatment paradigms into everyday clinical care. The multiple viewpoints expressed by the roundtable attendees illustrate the recognition that at this point, consensus has not been reached on the optimum algorithm for treatment of these patients. This article focuses on issues discussed during the roundtable from the perspective of the practicing cardiologist.

Effect of anemia on hemorrhagic complications and mortality following percutaneous coronary intervention.

The relation across anemia, hemorrhagic complications, and mortality associated with percutaneous coronary intervention (PCI) is unclear. We reviewed the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial, which compared bivalirudin plus provisional glycoprotein IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in patients undergoing urgent or elective PCI. Of the 6,010 patients randomized in REPLACE-2, 1,371 (23%) were anemic. Major bleeding was more common in anemic than in nonanemic patients (4.9% vs 2.8%, p = 0.0001). In anemic patients, treatment with bivalirudin (n = 678) resulted in a lower risk of major bleeding versus heparin plus glycoprotein IIb/IIIa blockade (n = 693, 3.5% vs 6.2%, p = 0.0221). Mortality was higher in anemic patients than in nonanemic patients at 30 days (0.9% vs 0.2%, p <0.0001), 6 months (2.6% vs 0.7%, p <0.0001), and 1 year (4.3% vs 1.5%, p <0.0001). There were no differences between anemic and nonanemic patients with regard to ischemic complications at 30 days. Although anemic patients had higher mortality rates, proportions of cardiovascular and noncardiovascular mortalities were equal in anemic and nonanemic patients. In conclusion, anemic patients undergoing PCI have an increased risk of mortality and major bleeding, but not of ischemic events, and the use of bivalirudin with provisional glycoprotein IIb/IIIa blockade decreases the risk of hemorrhagic complications compared with heparin plus planned glycoprotein IIb/IIIa blockade.

Predictors and impact of major hemorrhage on mortality following percutaneous coronary intervention from the REPLACE-2 Trial.

Patients undergoing percutaneous coronary intervention (PCI) have a significant risk of hemorrhagic complications. Predictors of major hemorrhage and its relation to mortality in PCI are not well defined. Baseline and periprocedural predictors of major hemorrhage and its impact on mortality in patients undergoing elective or urgent PCI randomly assigned to heparin plus planned glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin plus provisional GPIs in the REPLACE-2 Trial were determined. Of 6,001 patients, 3.2% experienced a major hemorrhage. Independent baseline predictors of major hemorrhage included advanced age, female gender, impaired creatinine clearance, and anemia. Independent periprocedural predictors of major hemorrhage included treatment with heparin plus GPI, increased procedural duration, provisional use of GPI, increased time to sheath removal, length of intensive care unit stay, and use of an intra-aortic balloon pump (all p <0.05). Mortality rates were higher in patients with than without major hemorrhage at 30 days (5.1% vs 0.2%), 6 months (6.7% vs 1.0%), and 1 year (8.7% vs 1.9%; p <0.001 for all). Furthermore, major hemorrhage was an independent predictor of 1-year mortality (odds ratio 2.66, 95% confidence interval 1.44 to 4.92, p = 0.002). In conclusion, in patients undergoing elective or urgent PCI, major hemorrhage was an independent predictor of 1-year mortality. A number of baseline and periprocedural factors independently predicted major hemorrhage, including treatment with heparin plus GPI.

Bleeding complications in acute coronary syndromes and percutaneous coronary intervention: predictors, prognostic significance, and paradigms for reducing risk.

In clinical trials up to 30% of patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) experience bleeding complications, and even higher rates have been reported in contemporary practice. A growing body of data suggests a strong correlation between bleeding and both short- and long-term adverse outcomes, including mortality, which is independent of baseline characteristics and remains evident in most trials, despite variations in the definition of major bleeding. Although the value of antithrombin and antiplatelet therapy in reducing the risk of ischemic events is well established, the mechanisms of action that confer the benefits of these therapies have an inherent tendency to increase the risk of bleeding complications. As a result, characterization of baseline hemorrhagic risk is critical and must be accomplished before selecting an antithrombotic therapy. Risk factors for bleeding may be divided into two categories: nonmodifiable (including age, gender, race, weight, renal insufficiency, anemia, and acuity of presentation) and modifiable (including choice of antithrombotic therapy and PCI procedural characteristics). Of these predictive factors, the choice, dosage, and duration of the antithrombin and/or antiplatelet regimen are perhaps the most readily modifiable, especially in patients with an increased risk of bleeding. This review explores the nature of the association between bleeding and adverse outcomes, including mortality; evaluates risk factors for bleeding; and examines mechanisms for reducing bleeding complications through the selection of appropriate antithrombotic therapy.