Efficacy and Safety of Cangrelor in Women Versus Men During Percutaneous Coronary Intervention: Insights From the Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PHOENIX) Trial.

BACKGROUND: Cangrelor is an intravenous ADP receptor antagonist that leads to potent and reversible inhibition of platelet aggregation. The relative safety and efficacy of some antiplatelet drugs in women has been disputed. METHODS AND RESULTS: The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PHOENIX) trial randomized 11,145 patients undergoing elective or urgent percutaneous coronary intervention to cangrelor or clopidogrel. The primary efficacy end point was the composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was GUSTO severe bleeding at 48 hours. Of subjects analyzed, 3051 (28%) were female. Cangrelor reduced the odds of the primary end point by 35% in women (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.48-0.89) and by 14% in men (OR, 0.86; 95% CI, 0.70-1.05; P interaction=0.23) compared with clopidogrel. Cangrelor reduced the odds of stent thrombosis by 61% in women (OR, 0.39; 95% CI, 0.20-0.77) and 16% in men (OR, 0.84; 95% CI, 0.53-1.33; P interaction=0.11). The odds of severe bleeding were similar in both women and men treated with cangrelor (0.3% versus 0.2%, P=0.30 [women]; 0.1% versus 0.1%, P=0.41 [men]; P interaction=0.88) versus clopidogrel. Cangrelor increased the odds of moderate bleeding in women (0.9% versus 0.3%, P=0.02), but not in men (0.2% versus 0.2%, P=0.68; P interaction=0.040). The net clinical benefit (primary efficacy and safety end point) favored cangrelor in both women (OR, 0.68; 95% CI, 0.50-0.92) and men (OR, 0.87; 95% CI, 0.71-1.06; P interaction=0.26). CONCLUSIONS: In CHAMPION PHOENIX, cangrelor reduced the odds of major adverse cardiovascular events and stent thrombosis in women and men and appeared to offer greater net clinical benefit than clopidogrel. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01156571.

Impact of cangrelor overdosing on bleeding complications in patients undergoing percutaneous coronary intervention: insights from the CHAMPION trials.

Overdosing of parenteral antithrombotic therapies can increase the risk of bleeding. Cangrelor is a potent intravenous platelet P2Y12 receptor antagonist with rapid onset and offset of action. In patients undergoing percutaneous coronary interventions (PCI), compared with control, cangrelor (30 µg/kg bolus, followed immediately by a 4 µg/kg per minute infusion for 2-4 h or until the conclusion of the index PCI, whichever was longer) reduces periprocedural thrombotic complications without an increase in major bleeding complications, although minor bleeding is increased. The impact of cangrelor overdosing on bleeding is unknown and represented the aim of this analysis. Patients with cangrelor overdosing were identified among safety population patients enrolled in the CHAMPION program (n = 25,107). Overdose was defined as administration of an excess >20 % of the bolus dose (30 µg/kg) and/or infusion rate (4 µg/kg per min). Bleeding complications were assessed. Among the safety analysis population in the CHAMPION program, 12,565 patients received cangrelor. A total of 36 overdosed cangrelor patients (0.29 %) were identified in this pooled analysis (20 with both bolus and infusion, 5 with bolus only, and 11 with infusion only). In the majority of patients, the dose did not exceed 2.5 times the recommended dose. Bleeding events were balanced between treatment arms and were consistent with those in the overall CHAMPION program. Only one overdosed patient experienced a serious bleed. There was no correlation between bleeding and magnitude of cangrelor overdose. In a large clinical trial program of patients undergoing PCI, cangrelor overdosing was rare and not associated with an increase in bleeding complications, an observation that may be attributed to its very short-half life and rapid offset of action.

Outcomes with cangrelor versus clopidogrel on a background of bivalirudin: insights from the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]).

OBJECTIVES: The aim of this study was to examine the efficacy and bleeding outcomes of cangrelor in patients in the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]) who underwent percutaneous coronary intervention with bivalirudin. BACKGROUND: Cangrelor is a potent intravenous P2Y12 inhibitor with rapid onset and offset. In the CHAMPION PHOENIX, cangrelor compared with clopidogrel significantly reduced 48-h ischemic events including stent thrombosis, without increasing major bleeding. Bivalirudin has demonstrated ischemic outcomes similar to those with heparin plus glycoprotein IIb/IIIa inhibition, with reduced bleeding but increased early stent thrombosis. METHODS: In the modified intent-to-treat population, 2,059 patients (18.8%) received bivalirudin, with 1,014 patients in the cangrelor treatment arm and 1,045 in the clopidogrel treatment arm. RESULTS: At 48 h, the primary endpoint of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis was lower with cangrelor versus clopidogrel (48 [4.7%] vs. 70 [6.7%]; odds ratio [OR]: 0.68, p = 0.047). Death was similar in both arms (2 [0.2%] vs. 2 [0.2%]). Myocardial infarction was reduced by cangrelor (37 [3.6%] vs. 59 [5.6%]; OR: 0.63, p = 0.03), as was death/myocardial infarction (39 [3.8%] vs. 61 [5.8%]; OR: 0.65, p = 0.04). Cangrelor was associated with a nonsignificant trend toward less stent thrombosis (7 [0.7%] vs. 15 [1.4%]; OR: 0.48, p = 0.10), which was evident within 2 h after percutaneous coronary intervention (p = 0.057). GUSTO (Global Use of Strategies to Open Occluded Arteries) severe bleeding was similar in both arms (2 of 1,021 [0.2%] vs. 2 of 1,055 [0.2%]) as were other bleeding definitions and transfusions. Efficacy and safety results were consistent in patients with stable angina, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction (p for interaction: 0.62 and 0.29). CONCLUSIONS: Cangrelor may offer an attractive benefit risk profile when used in combination with bivalirudin.

Impact of intraprocedural stent thrombosis during percutaneous coronary intervention: insights from the CHAMPION PHOENIX Trial (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention).

OBJECTIVES: This study sought to evaluate the clinical impact of intraprocedural stent thrombosis (IPST), a relatively new endpoint. BACKGROUND: In the prospective, double-blind, active-controlled CHAMPION PHOENIX (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention) trial, cangrelor significantly reduced periprocedural and 30-day ischemic events in patients undergoing percutaneous coronary intervention (PCI), including IPST. METHODS: An independent core laboratory blinded to treatment assignment performed a frame-by-frame angiographic analysis in 10,939 patients for the development of IPST, defined as new or worsening thrombus related to stent deployment at any time during the procedure. Adverse events were adjudicated by an independent, blinded clinical events committee. RESULTS: IPST developed in 89 patients (0.8%), including 35 of 5,470 (0.6%) and 54 of 5,469 (1.0%) patients in the cangrelor and clopidogrel arms, respectively (odds ratio: 0.65; 95% confidence interval: 0.42 to 0.99; p = 0.04). Compared to patients without IPST, IPST was associated with a marked increase in composite ischemia (death, myocardial infarction [MI], ischemia-driven revascularization, or new-onset out-of-laboratory stent thrombosis [Academic Research Consortium]) at 48 h and at 30 days (29.2% vs. 4.5% and 31.5% vs. 5.7%, respectively; p < 0.0001 for both). After controlling for potential confounders, IPST remained a strong predictor of all adverse ischemic events at both time points. CONCLUSIONS: In the large-scale CHAMPION PHOENIX trial, the occurrence of IPST was strongly predictive of subsequent adverse cardiovascular events. The potent intravenous adenosine diphosphate antagonist cangrelor substantially reduced IPST, contributing to its beneficial effects at 48 h and 30 days. (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX]; NCT01156571).

Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data.

BACKGROUND: Cangrelor is a potent, rapid-acting, reversible intravenous platelet inhibitor that was tested for percutaneous coronary intervention (PCI) in three large, double-blind, randomised trials. We did a pooled analysis of data from three trials that assessed the effectiveness of cangrelor against either clopidogrel or placebo in PCI. METHODS: This prespecified, pooled analysis of patient-level data from three trials (CHAMPION-PCI, CHAMPION-PLATFORM, and CHAMPION-PHOENIX) compared cangrelor with control (clopidogrel or placebo) for prevention of thrombotic complications during and after PCI. Trial participants were patients undergoing PCI for ST-elevation myocardial infarction (11.6%), non-ST-elevation acute coronary syndromes (57.4%), and stable coronary artery disease (31.0%). Efficacy was assessed in the modified intention-to-treat population of 24,910 patients, with a prespecified primary efficacy composite of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis at 48 h. The primary safety outcome was non-coronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe or life-threatening bleeding at 48 h. FINDINGS: Cangrelor reduced the odds of the primary outcome by 19% (3.8% for cangrelor vs 4.7% for control; odds ratio [OR] 0.81, 95% CI 0.71-0.91, p=0.0007), and stent thrombosis by 41% (0.5% vs 0.8%, OR 0.59, 95% CI 0.43-0.80, p=0.0008). Cangrelor reduced the odds of the secondary triple composite (all-cause death, myocardial infarction, or ischaemia-driven revascularisation at 48 h) by 19% (3.6% vs 4.4%, OR 0.81, 95% CI 0.71-0.92, p=0.0014). Efficacy outcomes were consistent across the trials and main patient subsets. These benefits were maintained at 30 days. There was no difference in the primary safety outcome (0.2% in both groups), in GUSTO moderate bleeding (0.6% vs 0.4%), or in transfusion (0.7% vs 0.6%), but cangrelor increased GUSTO mild bleeding (16.8% vs 13.0%, p<0.0001). INTERPRETATION: Compared with control (clopidogrel or placebo), cangrelor reduced PCI periprocedural thrombotic complications, at the expense of increased bleeding. FUNDING: The Medicines Company.

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.

Effect of platelet inhibition with cangrelor during PCI on ischemic events.

BACKGROUND: The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. METHODS: In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. RESULTS: The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P=0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P=0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P=0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. CONCLUSIONS: Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.).

Rationale and design of the Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON PHOENIX trial.

BACKGROUND: Despite robust efficacy in the reduction of ischemic events in patients who require percutaneous coronary intervention (PCI), current P2Y(12) inhibitors have limitations. In particular, they require hours to be effective, and they can only be administered orally. Cangrelor is an intravenous, potent, and reversible P2Y(12) inhibitor with fast onset and offset of action. We designed CHAMPION PHOENIX to evaluate the efficacy and safety of cangrelor in patients with atherosclerosis undergoing PCI. TRIAL DESIGN: The CHAMPION PHOENIX is a randomized, double-blind, double-dummy, superiority trial comparing cangrelor with clopidogrel standard of care in approximately 10,900 patients who have not previously received a P2Y(12) inhibitor and who require PCI, including patients with stable angina and with acute coronary syndromes (with or without ST-segment elevation). The primary objective of the study is to demonstrate that cangrelor will reduce the incidence of the composite of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis in the 48 hours after randomization compared with clopidogrel without excessive periprocedural bleeding. The key secondary objective is to demonstrate that cangrelor will reduce the incidence of stent thrombosis. Myocardial infarction will be defined according to the universal MI definition, adapting the definition of PCI-related (type 4a) MI. Bleeding will be assessed according to the thrombolysis in myocardial infarction, GUSTO, and Bleeding Academic Research Consortium (BARC) scales. CONCLUSION: The CHAMPION PHOENIX may establish the role of cangrelor in the care of patients who require PCI across the spectrum of stable and unstable coronary diseases in the setting of current treatment strategies.

Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials.

Cangrelor is an intravenous antagonist of the P2Y(12) receptor characterized by rapid, potent, predictable, and reversible platelet inhibition. However, cangrelor was not superior to clopidogrel in reducing the incidence of ischemic events in the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. A prospectively designed platelet function substudy was performed in a selected cohort of patients to provide insight into the pharmacodynamic effects of cangrelor, particularly in regard to whether cangrelor therapy may interfere with the inhibitory effects of clopidogrel. This pre-defined substudy was conducted in a subset of patients from the CHAMPION-PCI trial (n = 230) comparing cangrelor with 600 mg of clopidogrel administered before percutaneous coronary intervention (PCI) and from the CHAMPION-PLATFORM trial (n = 4) comparing cangrelor at the time of PCI and 600 mg clopidogrel given after the PCI. Pharmacodynamic measures included P2Y12 reaction units (PRU) assessed by VerifyNow P2Y12 testing (primary endpoint marker), platelet aggregation by light transmittance aggregometry following 5 and 20 µmol/L adenosine diphosphate stimuli, and markers of platelet activation determined by flow cytometry. The primary endpoint was the percentage of patients who achieved <20 % change in PRU between baseline and >10 h after PCI. The main trial was stopped early limiting enrollment in the platelet substudy. A total of 167 patients had valid pharmacodynamic assessments for the primary endpoint. The percent of individuals achieving <20 % change in PRU between baseline and >10 h after PCI was higher with cangrelor + clopidogrel (32/84, 38.1 %) compared with placebo + clopidogrel (21/83, 25.3 %), but this was not statistically significant (difference:12.79 %, 95 % CI: -1.18 %, 26.77 %;p = 0.076). All pharmacodynamic markers as well as the prevalence of patients with high on-treatment platelet reactivity were significantly lower in patients treated with cangrelor. A rapid platelet inhibitory effect was achieved during cangrelor infusion and a rapid offset of action after treatment discontinuation. This CHAMPION platelet function substudy represents the largest pharmacodynamic experience with cangrelor, demonstrating its potent P2Y(12) receptor inhibitory effects, and rapid onset/offset of action. Although there was no significant pharmacodynamic interaction when transitioning to clopidogrel therapy, further studies are warranted given that enrollment in this study was limited due to premature interruption of the main trial.

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.

Imiquimod 3.75% cream applied daily to treat anogenital warts: combined results from women in two randomized, placebo-controlled studies.

OBJECTIVE: To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts. METHODS: In two studies 534 women ≥12 years of age (mean 33.4) with 2-30 warts (mean 7.9) and total wart area ≥10 mm(2) (mean 166.3) were randomized (1:2:2) to placebo (106), imiquimod 2.5% (212) or 3.75% (216) creams applied once daily until complete clearance or a maximum of 8 weeks. RESULTS: For placebo, imiquimod 2.5% and 3.75%, respectively, complete clearance of all warts was achieved in 14.2%, 28.3%, and 36.6% of women (intent-to-treat, P = 0.008 imiquimod 2.5%, and P < 0.001 3.75% versus placebo). Mean changes in wart counts were -10.7%, -50.9%, and -63.5% (per-protocol, P < 0.001 each active versus placebo) and safety-related discontinuation rates 0.9%, 1.4%, and 2.3%. CONCLUSIONS: Imiquimod 3.75% applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts.

Mathematical determination of external defibrillators needed at mass gatherings.

OBJECTIVE: To develop a mathematical formula that assists in determining the number of automated external defibrillators (AEDs) needed at sites of mass gatherings. METHODS: Twenty (10 male, 10 female) healthy volunteers (equally divided between age groups 21-30 and 31-40 years) responded to mock cardiac arrests in a sports stadium. Seven different first-responder scenarios were simulated (ascending and descending three separate stairway slopes (22 degrees, 39 degrees, and 69 degrees ), as well as a response across a horizontal (0 degrees ) surface. To assess the impact of spectator congestion, the same volunteers conducted each scenario in an empty and full stadium. The quantitative relationship between time and distance was then plotted for each situation. Using the quantitative relationship, the area a first responder can cover in a specified time was calculated. RESULTS: The formula for the total number of AEDs needed in a stadium (or other mass gathering site) can be expressed as follows: Total AEDs=[A(1)/(Ds(1)xDh(1))]+[A(2)/(Ds(2)xDh(2))]+[A(3)/(Ds(3)xDh(3))] where A(1), A(2), and A(3) represent the total areas of a stadium with a slight, moderate, or steep stairway slope, respectively; Ds(1), Ds(2), and Ds(3) represent the stairway distance a first responder must ascend or descend for each slope; and Dh(1), Dh(2), and Dh(3) are the horizontal distances a responder can run in the time remaining. CONCLUSION: Given a medical director's targeted response times and goals, the optimal number of AEDs required at a mass gathering can be calculated using time versus distance relationships. Future studies should evaluate the impact of the mathematically derived optimal number of AEDs at mass gatherings.

Teaching ACLS stroke objectives to prehospital providers: a case-based approach.

OBJECTIVES: To determine whether a case-based educational module would increase prehospital care providers' short-term and long-term knowledge about stroke and to compare the educational impact when the module was moderated by a physician versus an advanced cardiac life support (ACLS) instructor. METHODS: A stroke module consisting of two case-based scenarios was administered to emergency medical services (EMS) personnel by either an ACLS instructor or a physician. Identical 25-question tests (based on 1997 ACLS prehospital stroke objectives) were administered before and after the module. Descriptive statistics were calculated by groups, and Wilcoxon tests were used to assess the significance of improvement in scores based on the paired data. RESULTS: Two hundred six EMS personnel [112 (54%) emergency medical technician (EMT)-P, 91 (44%) EMT-B/EMT-I, and three (2%) other training levels] participated in the module, of whom 74 [30 (41%) EMT-P, 42 (57%) EMT-B/EMT-I, and two (2%) other training levels] participated in follow-up testing between six and seven months. Overall, there was a 32% improvement in test scores immediately after completion of the module (p < 0.001) and an 18% improvement at six months (p < 0.001). No significant difference in pretest scores existed between the physician-led and ACLS instructor-led groups (mean EMT-P pretest scores 69% versus 70% and EMT-B/EMT-I scores 55% versus 54%, respectively). There was no significant difference in short-term (p = 0.36) or long-term (p = 0.074) score improvements between the two groups. CONCLUSION: This case-based approach to EMS stroke education is effective and can achieve equal benefit when administered by a physician or an ACLS instructor.

A randomized, controlled trial of panic disorder treatment initiation in an emergency department chest pain center.

STUDY OBJECTIVE: We examine the effect of a protocol for panic disorder recognition and treatment initiation on medication initiation rates and medication continuation rates at 1- and 3-month follow-up. METHODS: Enrolled participants, all at low to moderate risk for acute coronary syndrome, completed a 6-hour emergency department chest pain evaluation and panic disorder screen. Participants who had results positive for panic disorder completed the Panic Disorder Module of the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) by the research psychiatrist and the treating emergency physician, each blinded to the other's rating. Participants with panic disorder were randomized to either paroxetine initiation at 20 mg/d for 1 month or usual care with telephone follow-up at 3 months. RESULTS: Fifty (32%) of 156 enrolled participants met criteria for panic disorder. All 25 (100%) participants in the paroxetine group initiated treatment, compared with 6 (24%) in the usual care group initiating any form of treatment (P =.006, relative risk [RR] 2.58, 95% confidence interval [CI] 1.20 to 5.58). Fourteen (56%) participants continued paroxetine treatment for at least 1 month, and at 3 months, 9 (36%) continued on some antipanic medication, compared with 2 (8%) for the usual care group (P =.05, RR 3.57, 95% CI 0.84 to 15.8). CONCLUSION: Panic disorder is common and severe in this sample of patients with chest pain. A screening measure and a brief (5-minute) structured interview allowed emergency physicians with no extra training to reliably diagnose panic disorder and initiate pharmacologic treatment.

Diagnostic parameters of CK-MB and myoglobin related to chest pain duration.

OBJECTIVE: Cardiac marker sensitivity depends on chest pain duration at the time of sampling. Our objective was to estimate the sensitivity, specificity, and likelihood ratios of early CK-MB and myoglobin assays in patients presenting to the emergency department (ED) with nondiagnostic ECGs, stratified by the duration of ongoing chest pain at the time of ED assessment. METHODS: This was a prospective observational study carried out in 10 US and 2 Canadian EDs. Patients >25 years of age with ongoing chest pain and nondiagnostic ECGs were stratified by pain duration (0-4 h, 4-8 h, 8-12 h, >12 h). CK-MB and myoglobin assays were drawn at T = 0 (ED assessment) and T = 1 hr. Patients were followed for 7-14 days to identify all cases of acute myocardial infarction (AMI). ED test results were correlated with patient outcomes. RESULTS: Of 5005 eligible patients, 565 had AMI. Pain duration was 0-4 h in 3014 patients, 4-8 h in 961, 8-12 h in 487, and >12 h in 543. Marker sensitivity increased with pain duration, ranging from 28%-77% for CK-MB and 39%-73% for myoglobin. The maximal sensitivity achieved by a T = 0 assay was 73%, and this was in patients with 8-12 or >12 h of ongoing pain. No combination of tests achieved 90% sensitivity in any pain duration strata. CONCLUSIONS: Regardless of chest pain duration, single assays and early serial markers (0+1 hr) do not rule out AMI; therefore, serial assays over longer observation periods are required. Likelihood ratios derived in this study will help physicians who use Bayesian analysis to determine post-test AMI likelihood in patients with chest pain.