Antiplatelet therapy to prevent stroke: risk of brain hemorrhage and efficacy in atrial fibrillation.
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Biomedical subjects
Publications and source records attributed to R G Hart.
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Based on the hypothesis that managing pediatric death--particularly, communicating with survivors--is extremely difficult for most emergency physicians, 122 general emergency physicians at a written board review course were surveyed to assess their attitudes toward pediatric death. Sixty-six percent reported that communicating with the family of a child who had died was the most difficult experience in emergency medicine. Sixty-six percent considered communication with the family of a child who had died to be much more difficult than communication with the family of an adult who had died. Sixty-four percent reported feelings of guilt or inadequacy after unsuccessful pediatric resuscitation, and 47% reported feeling impaired for the remainder of their shift. Only 8% of physicians were aware of published guidelines regarding managing pediatric emergency department (ED) deaths, and only 14% of physicians had ever had any training in death notification. Ninety-two percent of physicians responded that a course directed toward managing the family of a child who had died in the ED would be helpful in dealing with this difficult situation.
BACKGROUND AND PURPOSE: The prothrombin time (expressed as the international normalized ratio [INR]) is the standard method of monitoring warfarin therapy in patients with atrial fibrillation. Prothrombin activation fragment F1.2 provides an index of in vivo thrombin generation and might provide a better index of the effective intensity of anticoagulation. We examined the relationship between F1.2 and INR in patients with atrial fibrillation. METHODS: We measured INR and F1.2 levels in 846 patients with atrial fibrillation participating in the Stroke Prevention in Atrial Fibrillation III study. Two hundred nineteen (26%) were taking aspirin alone, 326 (39%) were taking adjusted-dose warfarin, and 301 (36%) were taking a low fixed dose of warfarin (1 to 3 mg) plus aspirin (combination therapy). F1.2 levels were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients receiving adjusted-dose warfarin or combination therapy had significantly higher INR and significantly lower F1.2 values than those on aspirin alone (P < or = .0001 for each of the four comparisons). F1.2 values (nanomolar) were inversely correlated with INR (F1.2 = -0.1 + 2.3[1/INR]; R2 = .37; P < .0001; simple linear regression). However, significant variability remained. Among patients receiving warfarin, older patients had higher F1.2 values than younger patients after adjustment for INR intensity (P < .001) in the model. There was no difference in the relationship between F1.2 and INR between men and women. CONCLUSIONS: Increasing intensity of anticoagulation, as measured by the INR, is associated with decreasing thrombin generation as measured by the F1.2 level, but significant variability exists in this relationship. Older anticoagulated patients have higher F1.2 values than younger patients at equivalent INR values. The clinical significance of these differences is not clear. F1.2 measurement might provide information regarding anticoagulation intensity in addition to that reflected by the INR.
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BACKGROUND: Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. METHODS: To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. RESULTS: Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study. CONCLUSIONS: Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.
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The Stroke Prevention in Atrial Fibrillation II study compared the efficacy and safety of aspirin and warfarin in patients with atrial fibrillation. Three neurologists, blinded to patient therapy, categorized the pathophysiology of ischemic strokes that occurred in the trial based on predetermined clinical criteria. Upon analyzing the patients being treated with these two drugs, warfarin proved significantly more effective than aspirin in preventing cardioembolic strokes (p = 0.005) and strokes of uncertain pathophysiology (p = 0.01). There was no significant difference in the efficacy for prevention of noncardioembolic strokes.
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In addition to antithrombotic therapy, 2 treatment strategies for intermittent atrial fibrillation (AF) are evolving: suppression of AF or control of the ventricular response during AF. Clinical and echocardiographic features that predict recurrent AF may influence the choice of management. In this study, clinical, echocardiographic, and electrocardiographic data from 486 patients with intermittent AF enrolled in the Stroke Prevention in Atrial Fibrillation studies were analyzed. Patients with intermittent AF were younger (p < 0.001), had fewer incidences of systemic hypertension (p < 0.007) and heart failure (p < 0.001), and had more recent-onset AF than patients with constant AF. They also had a smaller mean left atrial diameter, a lower prevalence of a large (> 5 cm) left atrium, better left ventricular performance by echo, and less mitral regurgitation. After a mean follow-up of 26 months, 51% of patients remained in sinus rhythm and 49% of patients developed recurrent AF, including 12% who had AF, as seen on all follow-up electrocardiograms. Clinical factors predicting recurrent AF were age, heart failure, and myocardial infarction. An enlarged left atrium was associated with recurrent intermittent AF; an enlarged left ventricle predicted conversion to constant AF. Thus, clinical and echocardiographic parameters predict recurrent AF in patients with intermittent nonvalvular AF.
The prevalence of atrial fibrillation (AF) is related to age. Anticoagulation is highly effective in preventing stroke in patients with AF, but the risk of hemorrhage may be increased in older patients. We reviewed the available epidemiologic data to define the age and sex distribution of people with AF. From four large recent population-based surveys, we estimated the overall age- and gender-specific prevalence of AF. These estimates were applied to the recent US census data to calculate the number of men and women with AF in each age group. There are an estimated 2.2 million people in the United States with AF, with a median age of about 75 years. The prevalence of AF is 2.3% in people older than 40 years and 5.9% in those older than 65 years. Approximately 70% of individuals with AF are between 65 and 85 years of age. The absolute number of men and women with AF is about equal. After age 75 years, about 60% of the people with AF are women. In contrast to people with AF in the general population, patients with AF in recent anticoagulation trials had a mean age of 69 years, and only 20% were older than 75 years. The risks and benefits of antithrombotic therapy in older individuals are important considerations in stroke prevention in AF.
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