BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.
clinicaltrials.gov Identifier: NCT00091637.
Contributing factors are identified in the majority of SI patients. We recommend CT, ECG, echocardiography and blood cultures in all cases. Atrial fibrillation should be sought in older patients, while APLS and haematologic disorders should be suspected in younger ones. KEY MESSAGES There is no consensus regarding the diagnostic approach and management of splenic infarction. Cardiovascular disease and atrial fibrillation are the main causes for SI in elderly subjects while hematological, infectious and other causes are more prevalent in younger ones. Our data strongly suggests a high diagnostic yield for CT scan, ECG, blood culture and echocardiogram in every patient with SI.
Experimental and clinical observations suggest that thyroid hormone [L-thyroxine (T 4 ) and 3,5,30 -triiodo-Lthyronine (T 3 )] can support cancer cell proliferation. T 3 and T 4 promote both tumor cell division and angiogenesis by activating mitogen-activated protein kinase (MAPK) via binding to a hormone receptor on the avb3 integrin, overexpressed on many cancer cells. We have studied the responsiveness of several MM cell lines to T 3 and T 4 and characterized hormonal effects on cell survival, proliferation, and MAPK activation. Overnight T 3 (1-100 nmol/L) and T 4 (100 nmol/L) incubation enhanced, up to 50% (P < 0.002), MM cell viability (WST-1 assay) and increased cell proliferation by 30% to 60% (P < 0.01). Short exposure (10 minutes) to T 3 and T 4 increased MAPK activity by 2.5-to 3.5-fold (P < 0.03). Pharmacologic MAPK inhibition blocked the proliferative action of T 3 and T 4 . Antibodies to the integrin avb3 dimer and av and b3 monomers (but not b1) inhibited MAPK activation and subsequent cell proliferation in response to thyroid hormone, indicating dependence upon this integrin. Moreover, tetraiodothyroacetic acid (tetrac), a non-agonist T 4 analogue previously shown to selectively block T 3 /T 4 binding to avb3 receptor site, blocked induction of MAPK by the hormones in a dose-dependent manner. This demonstration of the role of thyroid hormones as growth factors for MM cells may offer novel therapeutic approaches. Mol Cancer Res; 9(10); 1385-94. Ó2011 AACR.
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