Four Studies on Stroke Treatment and Prevention

Dear colleagues, I am Christoph Diener, a neurologist from the University of Essen in Germany. This month I will review four articles on stroke that were published during the first few months of 2017.

Find-AF

I want to start with the Find-AF study,^[1] which was published in LancetNeurology. Studies of long-term ECG monitoring in patients with cryptogenic stroke have shown that the incidence of silent asymptomatic paroxysmal atrial fibrillation in this population is about 10% per year.^[2] A research group from the University of Göttingen, Germany, asked how many patients will develop atrial fibrillation after having an acute ischemic stroke rather than a cryptogenic stroke. Investigators recruited about 400 patients within 1 week of an acute ischemic stroke; patients were at least 60 years of age, did not have atrial fibrillation, and did not have a severe stenosis of the carotid artery. Patients were randomly assigned to receive standard-of-care 24-hour ECG versus 10 days of Holter monitoring at baseline, 3, and 6 months after enrollment. The primary endpoint was the new occurrence of atrial fibrillation.

After 6 months, 14% of those in the 10-day Holter monitoring group were found to have atrial fibrillation compared with 5% in the control, standard-of-care group. This shows that not only patients who have a cryptogenic stroke, but also other patients with stroke, have a relatively high risk of developing atrial fibrillation.

SOCRATES Subgroup

SOCRATES^[3] was a large trial with more than 13,000 patients who had a high-risk transient ischemic attack (TIA) or minor stroke. These patients were randomly assigned to receive ticagrelor or aspirin. Overall, the study was negative but differences in outcomes just missed the P value of .05 in favor of ticagrelor.

This new subgroup analysis^[4] looked at the 23% of patients who had ipsilateral atherosclerotic lesions in the carotid artery. As in the main study, the endpoint was stroke, myocardial infarction, or death after 90 days. In this analysis, there was a clear statistical benefit of ticagrelor over aspirin, with an odds ratio of 0.68; the event rate was 6% in the ticagrelor group versus 9.6% in the aspirin group, with no difference in bleeding complications.

This study clearly shows that we have to carefully select patients who are enrolled in secondary prevention trials. To me, it does not make a lot of sense to include people with lacunar strokes in these studies, and this is a good example of why. Unfortunately, ticagrelor is not yet approved for secondary prevention in people with high-risk TIA or a minor stroke.

Get With the Guidelines!

Next, I come to an extremely depressing paper^[5] that was published in JAMA. Get With the Guidelines is a huge registry in the United States that is aimed at improving outcomes for patients with stroke, atrial fibrillation, heart failure, and resuscitation. This study looked at more than 94,000 patients with atrial fibrillation who were admitted to a hospital after an acute ischemic stroke to learn what kind of anticoagulation treatment the patients were receiving at the time of stroke. In total, 7.6% of patients were on warfarin and 8.8% were on novel oral anticoagulants (NOACs). This means that 84% of these patients were not receiving anticoagulation.

In the group that was not (or not well) anticoagulated, 14% had subtherapeutic warfarin treatment, with INR levels below 2; 40% were being treated with aspirin, and about 30% were untreated. This clearly shows that we must do much better with anticoagulating patients with atrial fibrillation. There was an additional very important outcome: People who were adequately anticoagulated at the time of stroke had a much lower incidence of moderate or severe stroke, and they had a lower mortality.

Reversing Anticoagulation After Acute Stroke

Finally, I was involved in a study^[6] that examined the impact of using a reversal agent such as idarucizumab in patients who are anticoagulated with dabigatran after an acute ischemic stroke or a cerebral bleed. We looked at 19 people who had an acute ischemic stroke. They all received idarucizumab followed by systemic thrombolysis. The patients all did well, with no single case of bleeding complications. This shows that we can reverse dabigatran and use tissue plasminogen activator for thrombolysis in patients who are anticoagulated with dabigatran.

The more important group comprised 12 patients with intracranial bleeds while on dabigatran. After receiving the reversal agent, two of the patients had expansion of the hematoma and only one patient died. If we look at the results of imaging studies from warfarin and NOACs, the mortality of these intracranial bleeds is about 45% and half of the patients show a lesion growth.

These are small numbers but nonetheless indicate that the reversal agent may have an impact on how we treat patients on dabigatran who have acute ischemic stroke, and on how we treat patients on dabigatran who have an intracranial bleed.

Ladies and gentlemen, these are four interesting studies, all from the stroke field. I am Christoph Diener, a stroke neurologist from the University of Essen in Germany. Thank you very much for listening.

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