Angina/Non-ST-Elevation Myocardial Infarction : ACC/AHA 2007 Guidelines for the Management of Patients With Unstable ISSN: 1524-4539 Copyright © 2007 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX doi: 10.1161/CIRCULATIONAHA.107.18194

https://cdr.lib.unc.edu/downloads/vd66w2108

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction)...

Aspirin (ASA) is unique among current therapies because it acetylates cyclooxygenase (COX)-2 enabling the biosynthesis of R- containing precursors of endogenous antiinflammatory mediators. Here, we report that lipidomic analysis of exudates obtained in the resolution phase from mice treated with ASA and docosahexaenoic acid (DHA) (C22:6) produce a novel family of bioactive 17 R -hydroxy-containing di- and tri-hydroxy-docosanoids termed resolvins. Murine brain treated with aspirin produced endogenous 17 R -hydroxydocosahexaenoic acid as did human microglial cells. Human COX-2 converted DHA to 13-hydroxy-DHA that switched with ASA to 17 R -HDHA that also proved a major route in hypoxic endothelial cells. Human neutrophils transformed COX-2-ASA‐derived 17 R -hydroxy-DHA into two sets of novel diand trihydroxy products; one initiated via oxygenation at carbon 7 and the other at carbon 4. These compounds inhibited (IC 50 � 50 pM) microglial cell cytokine expression and in vivo dermal inflammation and peritonitis at ng doses, reducing 40‐80% leukocytic exudates. These results indicate that exudates, vascular, leukocytes and neural cells treated with aspirin convert DHA to novel 17 R -hydroxy series of docosanoids that are potent regulators. These biosynthetic pathways utilize omega-3 DHA and EPA during multicellular events in resolution to produce a family of protective compounds, i.e., resolvins, that enhance proresolution status.

https://rupress.org/jem/article-pdf/196/8/1025/1142248/jem19681025.pdf

Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals.

Context Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the. critically ill is poorly defined. Objectives To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. Design Prospective observational study conducted November 1999, with 2. components: a blood sampling study and an, anemia and blood transfusion study. Setting and Patients The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. Main Outcome Measures Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. Results The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r=0.34; P<.001) and total volume drawn (r=0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; chi(2)=50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; chi(2) =88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P=.02); the Kaplan-Meier log-rank test confirmed this difference. Conclusions This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.

https://jamanetwork.com/journals/jama/articlepdf/195310/jce10054.pdf

Anemia and blood transfusion in critically ill patients.

Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents.

Background— Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur. Methods and Results— The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment–elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103±8% of baseline), ADP-induced aggregation was reduced to 69±3%, 58±7%, and 33±12% of baseline, respectively, in patients in quartiles 2 through 4 (P<0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow...

Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction

http://www.faculty.umb.edu/pjt/epi/gum03.pdf

A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease.

We determined the prevalence and clinical predictors of aspirin resistance by prospectively studying 325 patients with stable cardiovascular disease who were receiving aspirin (325 mg/day for ≥7 days) but no other antiplatelet agents. We also compared the detection of aspirin resistance with optical platelet aggregation, a widely accepted method, with a newer, more rapid method, the platelet function analyzer (PFA)-100, a whole blood test that measures platelet adhesion and aggregation ex vivo. Blood samples were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate (ADP) and arachidonic acid, and by PFA-100 using collagen and/or epinephrine and collagen and/or ADP cartridges to measure aperture closure time. Aspirin resistance was defined as a mean aggregation of ≥70% with 10 μM ADP and a mean aggregation of ≥20% with 0.5 mg/ml arachidonic acid. Aspirin semiresponders were defined as meeting one, but not both of the above criteria. Aspirin resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time (≤193 seconds). By optical aggregation, 5.5% of the patients were aspirin resistant and 23.8% were aspirin semiresponders. By PFA-100, 9.5% of patients were aspirin resistant. Of the 18 patients who were aspirin resistant by aggregation, 4 were also aspirin resistant by PFA-100. Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women (34.4% vs 17.3%, p = 0.001) and less likely to be smokers (0% vs 8.3%, p = 0.004) compared with aspirin-sensitive patients. There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders (65.7 vs 61.3 years, p = 0.06). There were no differences in aspirin sensitivity by race, diabetes, platelet count, renal disease, or liver disease.

Profile and prevalence of aspirin resistance in patients with cardiovascular disease.

ContextAlthough aspirin has been shown to reduce cardiovascular morbidity and
short-term mortality following acute myocardial infarction, the association
between its use and long-term all-cause mortality has not been well defined.ObjectivesTo determine whether aspirin is associated with a mortality benefit
in stable patients with known or suspected coronary disease and to identify
patient characteristics that predict the maximum absolute mortality benefit
from aspirin.Design and SettingProspective, nonrandomized, observational cohort study conducted between
1990 and 1998 at an academic medical institution, with a median follow-up
of 3.1 years.PatientsOf 6174 consecutive adults undergoing stress echocardiography for evaluation
of known or suspected coronary disease, 2310 (37%) were taking aspirin. Patients
with significant valvular disease or documented contraindication to aspirin
use, including peptic ulcer disease, renal insufficiency, and use of nonsteroidal
anti-inflammatory drugs, were excluded.Main Outcome MeasureAll-cause mortality according to aspirin use.ResultsDuring 3.1 years of follow-up, 276 patients (4.5%) died. In a simple
univariable analysis, there was no association between aspirin use and mortality
(4.5% vs 4.5%). However, after adjustment for age, sex, standard cardiovascular
risk factors, use of other medications, coronary disease history, ejection
fraction, exercise capacity, heart rate recovery, and echocardiographic ischemia,
aspirin use was associated with reduced mortality (hazard ratio [HR], 0.67;
95% confidence interval [CI], 0.51-0.87; P = .002).
In further analysis using matching by propensity score, 1351 patients who
were taking aspirin were at lower risk for death than 1351 patients not using
aspirin (4% vs 8%, respectively; HR, 0.53 ; 95% CI, 0.38-0.74; P = .002). After adjusting for the propensity for using aspirin, as
well as other possible confounders and interactions, aspirin use remained
associated with a lower risk for death (adjusted HR, 0.56; 95% CI, 0.40-0.78; P<.001). The patient characteristics associated with
the most aspirin-related reductions in mortality were older age, known coronary
artery disease, and impaired exercise capacity.ConclusionAspirin use among patients undergoing stress echocardiography was independently
associated with reduced long-term all-cause mortality, particularly among
older patients, those with known coronary artery disease, and those with impaired
exercise capacity.

https://jamanetwork.com/journals/jama/articlepdf/194177/JOC10315.pdf

Aspirin Use and All-Cause Mortality Among Patients Being Evaluated for Known or Suspected Coronary Artery Disease: A Propensity Analysis

Distal embolization is the main potential risk of carotid stenting, and techniques to minimize this risk are evolving. Between July 1998 and March 2002, 305 consecutive patients who underwent elective or urgent percutaneous carotid intervention at The Cleveland Clinic were prospectively followed. During this period, the clinical practice of carotid stenting evolved from the routine use of glycoprotein IIb/IIIa inhibitors (GPIs) to routine emboli-prevention device (EPD) placement. A total of 199 patients received adjunctive GPIs (91% abciximab), and 106 patients underwent the procedure with an EPD (85% filter design, 15% occlusive balloon). At 30 days, the composite end point of neurologic death, nonfatal stroke, and major bleeding, including intracranial hemorrhage, was significantly lower among patients treated with EPDs compared with those treated with GPIs (0% vs 5.1%, p = 0.02). EPDs may provide an overall safer and more effective means of neuroprotection during carotid stenting than GPIs.

Patricia A. Gum

Papers

A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease.

Profile and prevalence of aspirin resistance in patients with cardiovascular disease.

Aspirin Use and All-Cause Mortality Among Patients Being Evaluated for Known or Suspected Coronary Artery Disease: A Propensity Analysis

Comparison of the safety and efficacy of emboli prevention devices versus platelet glycoprotein IIb/IIIa inhibition during carotid stenting

Aspirin Use and All-Cause Mortality Among Patients Being Evaluated for Known or Suspected Coronary Artery Disease