Background: Many physicians prescribe various combinations of aspirin, clopidogrel, and warfarin, as these treatments are endorsed in guidelines and expert statements. The use of these medications, however, has not been studied in a setting large enough to understand the safety of these therapies.
Study design: Retrospective cohort.
Setting: All Danish hospitals.
Synopsis: All hospitalized patients in Denmark from 1997 to 2006 who were identified with new onset atrial fibrillation (n=118,606) were monitored for outcomes and the use of aspirin, clopidogrel, and warfarin. These patients were followed for a mean of 3.3 years with the primary endpoint being admission to a hospital for a diagnosis of bleeding and a secondary endpoint of stroke.
Bleeding occurred in 13,573 patients (11.4%). The incidence of bleeding was highest in the first 180 days and then leveled off. Hazard ratios were computed with warfarin monotherapy as a reference. Only the hazard ratio for aspirin monotherapy (0.93) was lower (confidence interval [CI] 0.88-0.98). The highest risk of bleeding was with the triple therapy warfarin-aspirin-clopidogrel, which had a hazard ratio of 3.70 (CI 2.89-4.76).
For strokes, the hazard ratio was slightly better for warfarin-clopidogrel (0.70), although the CI was wide at 0.35-1.4 compared to warfarin monotherapy as a reference. Hazard ratios for monotherapy with clopidogrel or aspirin, dual therapy, and triple therapy all were worse, ranging from 1.27 to 1.86.
Bottom line: Warfarin as a monotherapy might have a bleeding risk comparable to that of aspirin or clopidogrel alone, and prevents more strokes than various combinations of these medications.
Citation: Hansen ML, Sørensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170 (16):1433-1441.
Cognitive and Physical Function Declines in Elderly Severe Sepsis Survivors
Clinical question: Is there a change in cognitive and physical functioning after severe sepsis?
Background: Disability is associated with increased mortality, decreased quality of life, and increased burdens by families and healthcare costs. After severe sepsis, the lasting effects of debility have not been investigated in any large studies.
Study design: Prospective cohort.
Setting: Hospitalized Medicare patients participating in the Health and Retirement Study.
Synopsis: Patients (n=1194) were followed for a minimum of one year between 1998 and 2006. The outcomes were measured by multiple personal interviews before and after a severe sepsis episode. Cognitive impairment was measured using three validated questionnaires dependent upon age or if a proxy was the respondent. For functional limitations, a questionnaire concerning instrumental and basic activities of daily living was used.
Cognitive impairment for those with moderate to severe impairment increased to 16.7% from 6.1% after a sepsis episode with an odds ratio of 3.34 (95% confidence interval 1.53-7.25). There was no significant increase in nonsevere sepsis hospitalized comparison patients (n=5574). All survivors with severe sepsis had a functional decline of 1.5 activities. The comparison group had about a 0.4 activity decline. All of these deficits endured throughout the study.
The authors provide comments that there should be a system-based approach in preventing severe sepsis, its burdens, and its costs. Suggestions include preventing delirium, initiating better standards of care, and involving therapists earlier to prevent immobility.
Bottom line: Severe sepsis is independently associated with enduring cognitive and physical functional declines, which strain families and our healthcare system.
Citation: Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-1794.