medwireNews: Adjunctive intra-arterial thrombolytic treatment during thrombectomy for acute ischemic stroke due to large vessel occlusion does not significantly increase the likelihood of patients being disability free at 90 days, suggest twin studies from China published in JAMA.
In the first study – POST-TNK – the adjusted risk ratio for being disability free 90 days after near-complete to complete endovascular thrombectomy (EVT) was a nonsignificant 1.15 with adjunctive intra-arterial tenecteplase versus no intra-arterial thrombolysis. The findings were similar for the second study – POST-UK – which compared intra-arterial urokinase with no intra-arterial thrombolysis, at a nonsignificant adjusted risk ratio of 1.13.
Freedom from disability was defined as a score of 0 or 1 point on the modified Rankin Scale (mRS), where 0 points equates to no symptoms and 6 points to death.
In a related editorial, Diederik Dippel (Erasmus University Medical Center, Rotterdam, The Netherlands) and colleagues highlight the researchers’ recognition that “each study by itself, although neutral, does not exclude a beneficial effect of adjunctive intra-arterial thrombolytics because the [confidence intervals] around the effect estimates include clinically important benefits.”
Yangmei Chen (The Second Affiliated Hospital of Chongqing Medical University, Yuzhong District, China) – an investigator on both studies – and POST-TNK co-authors explain that the trials were powered to detect a 13 percentage point improvement in freedom from disability with thrombolytic treatment, but the actual risk differences in both POST-TNK and POST-UK were around 5 percentage points.
“[T]here is agreement among clinician stakeholders that the minimum clinically important difference to change practice is 5%, and real-world physician and patient behavior indicates that the minimum clinically important difference for a simple, safe acute ischemic stroke treatment could be as low as 1.1% to 1.5%,” Chen et al note.
Both open-label, blinded studies were identical in design. For POST-TNK, 269 patients received intra-arterial tenecteplase at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) for 10–15 minutes through a distal access catheter or microcatheter, while 271 control patients received no intra-arterial thrombolytic treatment.
The participants had a median age of 69 years and 59.1% were men. Both groups had a median baseline National Institutes of Health Stroke Scale score (NIHSS) of 15 points, out of a possible 42 points, where higher scores signify more neurologic deficits, and a median Alberta Stroke Program Early Computed Tomography score (ASPECTS) of 8 points out of a possible 10 points, with higher scores indicating a smaller infarct core.
All the patients presented with stroke within 24 hours of feeling unwell, none had received intravenous thrombolysis prior to EVT, and all had an expanded Thrombolysis in Cerebral Infarction scale post-EVT of 2c to 3, where 3 equals complete reperfusion.
In all, 49.1% of patients assigned to receive tenecteplase were free of disability 90 days after EVT, compared with 44.1% of controls. Deaths in the first 90 days also occurred in a similar 16.0% and 19.3%, respectively, and although there was a numerically higher rate of symptomatic intracranial hemorrhage within 48 hours in the tenecteplase group, the difference was not significant (6.3 vs 4.4%).
For POST-UK, 267 patients were randomly assigned to receive intra-arterial urokinase at a single dose of 100,000 IU reconstituted with a 10 mL saline solution and the same number to receive no thrombolysis. The median age was 69 years, 58.2% were men, and the patient characteristics were comparable to those in POST-TNK.
The proportion of patients who were free of disability at 90 days was 45.1% in the urokinase treatment group and 40.2% in the control group. The rates of death at 90 days were 18.4% and 17.3%, respectively, and the rates of symptomatic intracranial hemorrhage within 48 hours were 4.1% and 4.1%, with all differences nonsignificant.
Editorialist Dippel points out that there are several ongoing trials examining the effect of periprocedural intra-arterial thrombolytics for ischemic stroke, such as the Safety and Efficacy of Intra-Arterial Tenecteplase for Non-Complete Reperfusion of Intra-Cranial Occlusions (TECNO) and Treatment of Persistent Distal Occlusion After Successful Proximal Recanalization in Thrombectomy (2BE3), and these “may provide more evidence to the efficacy of periprocedural intra-arterial thrombolytics in ischemic stroke patients.”
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