Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio.Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death.The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent.Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
To the Editor.— The cat's eye reflex, first noticed in 1765 in an infant by its father,1is the most common presenting sign in retinoblastoma. Strabismus is the second most common sign.2 The early amaurotic cat's eye is often a white, yellow, or pinkish and nonreproducible pupillary flash best noted under diminished natural illumination. On physical examination with extraocular illumination, replacement of the normal red pupillary reflex with a white reflex may be observed. A relatively small tumor will elicit the reflex when located at the posterior pole of the eye, whereas tumors located in the retinal periphery must be larger2and the reflex is more apt to be instantaneous and nonreproducible. Other causes of a white reflex are tuberous sclerosis, angiomatosis, inflammatory lesions such as parasites, and congenital malformations of the eye, such as retinal dysplasia and hyperplastic vitreous.3 The Figure brilliantly demonstrates the
