Bleeding in very old patients on vitamin K antagonist therapy.

A common topic in clinical anticoagulation research used to be bleeding risk in old age. Times have changed, as well as the population of patients on anticoagulants, and the topic now is bleeding risk in very old patients. What is it about age that stimulates clinical investigators to launch studies of age and bleeding risk with vitamin K antagonist (VKA) therapy? First, the decision to initiate a VKA must always follow a consideration of the risks and benefits of therapy, regardless of age, and one should have a reasonable knowledge of the risk of bleeding at various age intervals. Second, the elderly, however defined, are the major users of oral anticoagulants because the 2 most common indications for such treatment, atrial fibrillation (AF) and venous thromboembolism, are most prevalent in the elderly. Third, a number of studies suggest that older individuals are at greater risk of bleeding than their younger counterparts with similar diagnoses.1–4 Fourth, the perception, real or not, that older age is associated with a greater risk of bleeding represents a barrier to the treatment of the elderly with oral anticoagulants for well-established indications. Multiple studies document that individuals with AF are undertreated or not treated at all with VKA therapy, thus denying one of the most effective stroke prevention therapies to a large segment of the population most in need.5–8 The consequence of this paradox is exemplified by the recent Apixaban versus Acetylsalicylic Acid to Prevent Strokes (AVERROES) study with a new direct factor Xa inhibitor, apixaban, in which investigators randomized patients with AF who were thought to be poor candidates for a VKA (mean age, 70 10 years) to apixaban versus aspirin.9 The principal criticism of this study was the rationale behind the decisions not to treat patients with a VKA, which in many cases was that they were thought to be at too high a risk for such therapy.10 The outcome overwhelmingly favored the anticoagulant, as was the case in trials of warfarin versus aspirin in AF,11 without an increased incidence of major bleeding compared with aspirin alone, thus indicating that anticoagulation therapy really is safe for these individuals. Finally, there are ongoing debates and contradictory evidence12 as to whether older age is a risk factor for major bleeding and, if so, if is it an independent risk factor for major bleeding. A number of bleeding risk indexes incorporate age as an independent risk factor and have been validated prospectively such as the Outpatient Bleeding Risk Index,13 the HEMORR2HAGES score,14 and the HAS-BLED index.15