LeRoy LeNarz

Mortality Benefit With Prasugrel in the TRITON–TIMI 38 Coronary Artery Bypass Grafting Cohort : Risk-Adjusted Retrospective Data Analysis

OBJECTIVES The objective of this study was to characterize the bleeding, transfusion, and other outcomes of patients related to the timing of prasugrel or clopidogrel withdrawal before coronary artery bypass grafting (CABG). BACKGROUND There is little evidence to guide clinical decision making regarding the use of prasugrel in patients who may need urgent or emergency CABG. Experience with performing CABG in the presence of clopidogrel has raised concern about perioperative bleeding complications that are unresolved. METHODS A subset of the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38), in which patients with acute coronary syndrome were randomized to treatment with aspirin and either clopidogrel or prasugrel, underwent isolated CABG (N = 346). A supplemental case report form was designed and administered, and the data combined with the existing TRITON-TIMI 38 database. Baseline imbalances were corrected for using elements of the European System for Cardiac Operative Risk Evaluation and The Society of Thoracic Surgeons predictive algorithm. RESULTS A significantly higher mean 12-h chest tube blood loss (655 ± 580 ml vs. 503 ± 378 ml; p = 0.050) was observed with prasugrel compared with clopidogrel, without significant differences in red blood cell transfusion (2.1 U vs. 1.7 U; p = 0.442) or the total donor exposure (4.4 U vs. 3.0 U; p = 0.463). All-cause mortality was significantly reduced with prasugrel (2.31%) compared with 8.67% with clopidogrel (adjusted odds ratio: 0.26; p = 0.025). CONCLUSIONS Despite an increase in observed bleeding, platelet transfusion, and surgical re-exploration for bleeding, prasugrel was associated with a lower rate of death after CABG compared with clopidogrel.

Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials ∗

BACKGROUND Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. METHODS Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. RESULTS The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27); transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. CONCLUSIONS Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.

Effect of prasugrel pre-treatment strategy in patients undergoing percutaneous coronary intervention for NSTEMI: the ACCOAST-PCI study.

BACKGROUND After percutaneous coronary intervention (PCI) for non-ST-segment elevation myocardial infarction (NSTEMI), treatment with a P2Y12 antagonist with aspirin is recommended for 1 year. OBJECTIVES The oral P2Y12 antagonists ticagrelor and prasugrel have higher recommendations than clopidogrel, but it is unknown if administration before the start of PCI is beneficial. METHODS In the randomized, double-blind ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction) trial, 4,033 patients were diagnosed with NSTEMI and 68.7% underwent PCI; 1,394 received pre-treatment with prasugrel (30-mg loading dose), and 1,376 received placebo. At the time of PCI, patients who received pre-treatment with prasugrel received an additional 30-mg dose of prasugrel, and those who received placebo received a 60-mg loading dose of prasugrel. Primary efficacy was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization. Investigators captured the presence of thrombus on initial angiography and during PCI. RESULTS The incidence of the primary endpoint through 7 days from randomization in the pre-treatment group versus the no pre-treatment group was 13.1% versus 13.1% (p = 0.93). Pre-treatment with prasugrel was not associated with decreases in any ischemic event, including total mortality. Patients with thrombus on angiography had a 3-fold higher incidence of the primary endpoint than patients without thrombus. There was no impact of pre-treatment with prasugrel on the presence of thrombus before PCI or on occurrence of stent thrombosis after PCI. There was a 3-fold increase in all non-coronary artery bypass graft Thrombolysis In Myocardial Infarction (TIMI) major bleeding and a 6-fold increase in non-coronary artery bypass graft life-threatening bleeding with pre-treatment with prasugrel; the same trends persisted in patients who had radial or femoral access even with use of a closure device. CONCLUSIONS These findings support deferring treatment with prasugrel until a decision is made about revascularization in patients with NSTEMI undergoing angiography within 48 h of admission. (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction [ACCOAST]; NCT01015287).

Management of esophageal gunshot wounds.

The records of 20 patients with gunshot wounds of the esophagus seen from 1973 through 1985 were reviewed. Nine perforations were cervical, 10 were thoracic, and 1 was abdominal. Because physical findings and plain roentgenograms lack specificity, a high index of suspicion based on the path of the bullet tract is essential for early diagnosis. Esophageal injury should especially be suspected when the bullet wound is transcervical or transmediastinal. Perforation was diagnosed by esophagoscopy in 9 patients, esophagography in 4, and surgical exploration in 7. Mean time from admission to operation was 3.8 hours. Associated injuries occurred frequently. Eighteen patients were treated by primary closure and wide drainage, and 2 were managed by esophageal exclusion. There were 2 perioperative deaths, both in patients with associated aortic injuries, and 1 late death, for an overall mortality of 15%. There was one postoperative leak following a cervical repair. No leaks occurred in patients having a thoracic repair. The findings indicate that esophageal perforation must be sought by a variety of methods. With prompt diagnosis and early operation, primary repair can be safely accomplished. When sepsis from esophageal leak is avoided, mortality and major morbidity are related to associated injuries.

Factors associated with clopidogrel use, adherence, and persistence in patients with acute coronary syndromes undergoing percutaneous coronary intervention

Abstract Objective: Recent guidelines recommend use of aspirin and either clopidogrel or prasugrel for at least 12 months following use of drug-eluting or bare metal stents in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). This study evaluated factors associated with clopidogrel use and adherence in ACS patients following PCI. Research design and methods: The US employer-based MarketScan commercial claims database was used to examine factors associated with clopidogrel use and adherence. Adherence was defined as a medication possession ratio of 80% or higher. Multivariate logistic regression analyses were conducted to identify factors associated with clopidogrel use and adherence and included patient demographics, comorbidities, and prior beta-blocker, statin, and angiotensin converting enzyme inhibitor (BSI) use as factors. Results: A total of 10,465 patients aged 18–65 years who met inclusion criteria were hospitalized for ACS and underwent PCI between 01/01/2005 and 12/31/2006. Overall, the rate of clopidogrel use was 92.8% for ACS-PCI patients and 66.8% of the clopidogrel users were adherent. Receiving PCI without stenting (Odds Ratio [OR] = 3.28), comorbid hypertension (OR = 1.50), diabetes (OR = 1.49), and atrial fibrillation (OR = 1.91) were associated with decreased filled prescriptions for clopidogrel. Younger age (OR = 0.83) and prior use of clopidogrel (OR = 0.54) or other BSI medications (OR = 0.44) were associated with increased use of clopidogrel (all p values < 0.05). Factors significantly associated with non-adherence of clopidogrel were prior use of clopidogrel (OR = 1.40), prior hospitalization (OR = 1.34), chronic pulmonary disease (OR = 1.31), PCI without stenting (OR = 1.32), diabetes (OR = 1.17), and younger age (OR = 1.29). Prior use of BSI medications (OR = 0.82) increased adherence to clopidogrel. Conclusions: Prior use of clopidogrel, comorbid conditions such as diabetes and chronic pulmonary disease, prior hospitalization, PCI without stenting, and younger age had a negative impact on clopidogrel adherence. These findings may assist programs to improve thienopyridine compliance through a better understanding of patients’ disease profiles and concomitant medication use.

Transfusion outcomes in patients undergoing coronary artery bypass grafting treated with prasugrel or clopidogrel: TRITON-TIMI 38 retrospective data analysis

OBJECTIVE Coronary artery bypass grafting-related bleeding and associated transfusion is a concern with dual antiplatelet therapy in patients with acute coronary syndromes. The objective of the present study was to characterize a potential risk-adjusted difference in transfusion requirements between prasugrel and clopidogrel cohorts. METHODS The data from 422 patients undergoing isolated coronary artery bypass grafting from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 were analyzed retrospectively. RESULTS We found no difference in baseline transfusion risk scores between cohorts. As predicted, the number of units of red blood cells transfused perioperatively correlated with the transfusion risk score (P < .0001). Overall, the 12-hour chest tube drainage volumes and platelet transfusion rates in the prasugrel cohort were significantly greater. However, no statistically significant differences were found in the number of red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure. A significantly greater number of platelet units were transfused postoperatively in the prasugrel patients who underwent surgery within 5 days or less after withdrawal of drug. In an analysis adjusted for the predicted risk of mortality, total donor exposure was not associated with increased mortality. CONCLUSIONS The use of prasugrel compared with clopidogrel was associated with greater 12-hour chest tube drainage volumes and platelet transfusion rates but without any significant differences in red blood cell transfusions, total hemostatic components transfused, or total blood donor exposure.

Resource utilization and healthcare costs for acute coronary syndrome patients with and without diabetes mellitus

Abstract Objective: This study compared differences in healthcare costs and resource utilization for acute coronary syndrome (ACS) patients with and without diabetes mellitus (DM). Methods: A retrospective cohort study of a large, US employer-based claims database identified adults hospitalized for ACS between 01/01/2005 and 12/31/2006 and categorized them based on DM status. Resource utilization and costs during the index hospitalization and in the 12-month follow-up period were compared for ACS patients with and without DM using the propensity score stratification bootstrapping method, adjusting for differences in demographic and clinical characteristics. Results: Of 12,502 patients who met selection criteria, 3,040 (24%) had a history of DM and 9,462 (76%) did not. Patients with DM were older, female, and had higher rates of previous cardiovascular and renal diseases. After the propensity score stratification, patients with DM incurred higher index hospitalization costs (

Predictors of bleeding in patients with acute coronary syndromes treated with prasugrel

32,577 vs.

Impact of prasugrel pretreatment and timing of coronary artery bypass grafting on clinical outcomes of patients with non-ST-segment elevation myocardial infarction: From the A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST-Elevation Myocardial Infarction (ACCOAST) study.

29,150, p < 0.01) as well as higher total follow-up healthcare costs (

Factors associated with statin selection among privately insured commercial and Medicare patients.

35,400 vs.