Antithrombotic therapy after cerebral hemorrhages.

Cerebral Hemorrhages To the Editor: Oral anticoagulation (OAC) generally increases the likelihood of intracerebral hemorrhage (ICH). When there is an indication for OAC in a patient with a history of ICH, the clinician is in the difficult situation of assessing risks and benefits of OAC. In the absence of data from clinical trials, Eckman et al1 have used a decision-analysis model to compare the expected values of 3 treatment strategies— OAC, aspirin, and no antithrombotic therapy—in patients with ICH and atrial fibrillation (AF).1 They conclude that all survivors of lobar ICH and most survivors of deep hemispheric ICH with AF should not be offered OAC. Only patients with deep hemispheric ICH at high risk for stroke or embolism or low risk of ICH recurrence might benefit from OAC.1 Before these recommendations are integrated into clinical practice, several assumptions in the decision-analysis model have to be clarified: 1. The origin of ICH is multifactorial. Some underlying pathologies such as vascular malformations or vasculitis are treatable. For others, no causal treatment is available. Cause and treatment influence the recurrence rate of ICH. Thus, in a patient with ICH and indication for OAC, the ICH origin has to be assessed, as does whether there was any kind of treatment. We miss this kind of evaluation in the model assumptions. Possibly, the assumption is that all “secondary” causes of ICH like vascular malformations, tumors, hemorrhagic infarcts, trauma, and vasculitis have been definitively excluded. If this is the case, it should be stated. 2. For patients with lobar ICH, a high annual recurrence rate of 15% is assumed on the basis of 1 study with 71 patients that also included patients with a previous ICH before the index ICH.2 This rate is much higher than the 0.0% to 5.7% reported by other studies.3 For patients with deep hemispheric ICH, an annual recurrence rate of 2.1% is assumed on the basis of a review of 4 studies.3 Why did the authors use data from a single study for calculation of the recurrence rate of lobar ICH and not aggregated data like they have used for deep hemispheric ICH? How would the outcome of the analysis change if the recurrence rate of lobar ICH were assumed to be 5.4%, as suggested by aggregated data?3 3. The assumption that the site of the index ICH is predictive for the recurrence rate is further modified by a study of 243 patients that found no influences of the site of ICH on the recurrence rate, which was 2.1% per year.4 4. The effect of OAC on recurrent ICH is assumed as a relative risk of 2. This is rather low in view of the findings of a study in which OAC was initiated in 25 patients after the index ICH and tripled the risk of recurrent ICH.4 How would the outcome change if a relative risk of 3 were assumed as the effect of OAC on recurrent ICH? 5. It is unclear why an annual risk of stroke of 4.5% is assumed. The risk for stroke/embolism depends on age and the risk factors of hypertension, diabetes, stroke, or transient ischemic attack. Depending on these factors, the annual rate of stroke/embolism varies between 1.0% and 8.9%.5 From these data, the 69-year-old man, on whom the base case focused, has an annual risk of stroke/embolism of 4.3% if he was without risk factors and of 5.7% if he had 1 risk factors. 6. Aspirin is recommended as an alternative to OAC. Aspirin dosages, however, shown to be effective in preventing stroke/ embolism in AF are 300 mg/d.6 Because of gastrointestinal side effects, these dosages might frequently not be tolerated as a longterm therapy. Furthermore, the rate of aspirin-associated ICH in patients with ICH is unknown. Possibly, pathomechanisms such as amyloid angiopathy play a role in aspirin-associated and in OACinduced ICH.7 Facing these uncertainties, a decision-analysis model may be misleading. On the basis of controversially assessed and “soft” assumptions, the results of the model might pretend “objective” results. There is a need for clarification of risk factors for ICH during OAC. MR gradient-echo imaging or assessment of genetic factors may be helpful. In the meantime, we recommend that, in patients with prior ICH and an indication for OAC, all available information should be collected. Additionally, an extensive evaluation concerning the cause of the ICH should be performed. Knowledge about the potential cause of the ICH and the patient’s present condition will enable us to estimate recurrent ICH risk. If the cause of the ICH cannot be assessed, the decision about OAC has to be individualized.