Each year, the world’s neurologists gather to unveil their latest innovations at the International Stroke Conference (ISC). Other specialties have similar conferences, but neurology exerts an outsized effect on emergency department operations as stroke treatment continues to evolve. This year’s ISC, held in New Orleans, found curiosities across the spectrum of acute stroke care potentially affecting workflow, if not already reflected in the workflow of some departments.
Explore This IssueACEP Now: Vol 41 – No 05 – May 2022
One important clinical question facing neurologists remains the consequence of direct oral anticoagulants on acute stroke care. The current American Heart Association Stroke Guidelines advise against the use of thrombolytic therapy in patients taking novel oral anticoagulants (NOACs)—rivaroxaban, apixaban, edoxaban, dabigatran—unless specific coagulation measures are normal or at least 48 hours have passed since their most recent dose. This recommendation has effectively evolved from prior observations regarding the increase in intracranial hemorrhage associated with thrombolysis in patients concurrently taking warfarin. However, some controversy exists, as the NOACs are generally viewed as having a relatively reduced risk for intracranial hemorrhage as compared to warfarin.
Presented at ISC 2022, a retrospective evaluation of the American Stroke Association registry attempts to add further clarity to this question. Using 163,038 patients treated with alteplase between 2015 and 2020, the authors compared outcomes for patients recorded as taking a NOAC within seven days of hospital arrival with those taking no NOAC. Their primary outcome was that of safety, looking to see if patients taking NOACs were more likely to suffer symptomatic intracranial hemorrhage.
Overall, across the entire cohort of patients who were not taking an oral anticoagulant, the rate of intracranial hemorrhage following thrombolysis was 3.2 percent. For those patients having been recorded as taking a NOAC, the unadjusted rate was 3.7 percent. In the adjusted analysis, as baseline characteristics of those taking a NOAC obviously differ from those who do not, even this small difference in intracranial hemorrhage vanishes. Further analyses of secondary outcomes, such as inpatient mortality and functional outcomes, showed a mix of findings not reliably favoring one cohort or the other.
Retrospective analyses may be potentially biased in several respects. The most obvious issue here is selection bias. During the study period, 22,977 patients taking NOACs arrived at hospitals within the time frame potentially eligible for thrombolysis, but only 2,207 were treated. It is overwhelmingly likely this subset of patients recorded as taking NOACs were chosen by treating clinicians to receive thrombolysis because they demonstrated the most favorable risk/benefit profile. For example, patients selected may have missed their most recent dose of NOAC, may have had coagulation studies specifically supporting treatment with thrombolysis or may have undergone NOAC reversal with a binding agent such as idarucizumab. These important selection biases are not captured in the registry data and severely limit any potential conclusions drawn. It is absolutely not the case that any local procedures or treatment decisions ought to be changed based on these data as presented.
The next bit of curiosity presented at the ISC meeting relates to potential treatment decisions in patients considered for endovascular intervention. The idealized approach to endovascular intervention involves clot retrieval for large vessel occlusions with only a small core infarct surrounded by a large region of reduced perfusion supplied by collateral circulation. Larger core infarcts are considered, generally, on a case-by-case basis, with lower expectations of benefit and greater concern for harm. This study, RESCUE-Japan, randomized patients with stroke from large vessel occlusion and substantial infarct visible on initial imaging, as judged by The Alberta Stroke Program Early CT Score of three to five.
The most immediately apparent finding from these data indicates how dramatically poor the outcomes were for these patients. Patients randomized to medical therapy alone achieved a modified Rankin Score (mRS) of 0–3, the primary outcome for the study, only 12 percent of the time. This cohort suffered severely from disabling strokes, as a patient with mRS 3 exhibits moderate disability but is still able to walk independently. Endovascular intervention was able to improve the percentage of those achieving this primary outcome to 31 percent. Most patients achieved only mRS 2 and 3 but did so in dramatically greater proportion than those managed with medical therapy alone. It is quite likely, if your endovascular team is not already taking patients with large core infarcts for intervention, this study should tip the scales in favor of the procedure.
Finally, the CHOICE randomized clinical trial findings were presented. This trial investigated the value of adding intra-arterial alteplase to standard endovascular therapy for large vessel occlusion. In general, this addresses the concern that clot retrieval is still associated with substantial microcirculatory thrombi following large vessel intervention. In this study, those treated with intra-arterial alteplase achieved mRS 0–1 in 59 percent of the cases, while those receiving placebo did so only 40 percent of the time. Limitations include low enrollment due to the impact of the COVID-19 pandemic, but these data support cautious use of intra-arterial alteplase awaiting further confirmatory investigation.
These trials presented at the International Stroke Conference will likely affect the processes of care and outcomes of patients coming through the emergency department with acute stroke.