Possible timing for anticoagulation therapy initiation in ischemic stroke patients with atrial fibrillation: further analysis of the hemorrhagic transformation index

Objective: to assess the risk of hemorrhagic transformation (HT), by taking into account an appropriate scale (the hemorrhagic transformation index (HTI)) to clarify the possible timing of anticoagulant therapy (AT) initiation in patients with atrial fibrillation (AF) and ischemic stroke (IS) in the middle cerebral artery (MCA) bed.

Patients and methods. The admission data of 304 consecutively selected patients (111 men and 193 women aged 32 to 94 years (mean age, 72.7 years) with any form of AF and IS in the MCA basin were analyzed. The end point of the study was any HT according to brain computed tomography findings in the first 2 weeks after the development of IS. The HTI scores were divided into categories based on their predicted HT probabilities, thus yielding four models. Their comparison with the standard (the Diener rule) and the choice of the most appropriate model were done using the binary logistic regression and appropriate analysis (receiver operating characteristic, ROC). The final HTI model and the Diener rule were further used in the Royston–Parmar survival analysis to predict the risk of HT by days after the onset of IS. This was used to plot hazard function and survival, as well as the number of patients to be treated (number needed to treat, NNT) and the number of patients who can be harmed (number needed to harm, NNH). Possible periods for AT initiation were determined by the NNT and NNH plots.

Results and discussion. All the HTI models under study were superior to the Diener's rule in the accuracy of HT prediction. However, the HTI model with 0–1, 2–3, 4–5, 6–8 score arrangements was found to be the best one, as shown by the results of tests; it could additionally identify patients at very high (>0.8) risk for HT and somewhat better differentiate patients at low (0.05–0.1) risk. A survival analysis showed that the hazard function peaked on 1 and 3 days after the onset of IS. There was a progressive NNT drop in patients with a HTI score of 0–1 on 1 to 3 days; their curves reached a plateau on day 4. In patients with a HTI score of 2–3, NNT declined on days 1 to 4, with a plateau on day 5. In those with a HTI score of 4–5, NNH was minimal within the first 3 days following the onset of IS, and then there was a significant NNH rise until the end of the second week. In patients with a HTI score of 6–8, NNH remained very low throughout the follow-up period with a significant increase on days 4 to 9, with a subsequent exit to the plateau.

Conclusion. The greatest risk of HT is observed on 1 and 3 days after the onset of IS. AT is recommended to patients with a HTI score of 0–1 on day 4 after the onset of IS, to those with a HTI score of 2–3 on day 5, and to those with a HTI score of 4–5 following 2 weeks. AT may be initiated in patients at very high risk for HT (a HTI score of 6–8) on 9 days, provided that HT is absent.

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