PracticeUpdate Cardiology March 2019

ISC 2019 21

Some Stroke Patients May Benefit FromThrombolysis Beyond Standard 4.5-Hour TimeWindow EXTEND trial reveals that the presence of ischemicpenumbrameansalteplasemayprove beneficial up to 9 hours after stroke onset. S troke patients with evidence of ischemic penumbra on advanced imaging may benefit from thrombolytic therapy even if their symptoms began more than 4.5 hours earlier, according to a presentation at ISC 2019. During his presentation, Henry Ma, MD, of Monash Uni- versity in Melbourne, Australia, explained that current guidelines for thrombolysis in acute ischemic stroke rec- ommend it is used only in patients who present within 4.5 hours of stroke onset. Advanced imaging, however, sug- gests that ischemic penumbra can remain up to 24 hours after stroke onset, and salvaging this penumbra may lead to improved clinical outcomes. Thus, using advanced imag- ing to identify patients with ischemic penumbra may help detect those who would benefit from thrombolysis beyond the standard 4.5-hour time window. Dr. Ma and colleagues conducted the multicenter, rand- omized, double-blind, placebo-controlled EXTEND trial, which evaluated use of alteplase 0.9 mg/kg among patients who presented with ischemic stroke within 4.5 to 9 hours from stroke onset or those with wake-up stroke, meaning they awoke in the morning with symptoms of stroke. Patient selection was based on automated perfusion imaging soft- ware showing salvageable brain tissue (CT perfusion or MR diffusion/perfusion). The primary endpoint of the trial was excellent functional outcome, defined as a modified Rankin Score (mRS) of 0 to 1 at 3 months. The initial intent of the trial was to recruit 310 patients, but the trial was stopped early after accruing 225 patients (113 given alteplase and 112 given placebo) due to loss of clin- ical equipoise based on other trial results. Based on an intent-to-treat analysis, patients who received alteplase were more likely to achieve an excellent func- tional outcome at 3 months (35% vs 29%, adjusted risk ratio 1.44, P = .042). They were also more likely to achieve a good functional outcome, defined as an mRS 0 to 2 (50% vs 43%, adjusted risk ratio 1.36, P = .017) at 3 months as well as increased early reperfusion (50% vs 28%, adjusted risk ratio 1.73 P = .002) and clinical improvement (National Institutes of Health Stroke Score reduction 22% vs 10% adjusted risk ratio 2.51, P = .006) at 24 hours. Mortality was similar in both groups (12% vs 9%, adjusted risk ratio 1.17 P = .665), but there was a trend toward an increased risk of symptomatic intracranial hemorrhage with alteplase (6% vs 1%, adjusted risk ratio 7.22 P = .053). During his presentation, Dr. Ma pointed out that this is the first trial to demonstrate the benefits of thromboly- sis therapy in an extended time window using automated penumbral imaging. www.practiceupdate.com/c/79802

Late Thrombectomy for Stroke LinkedWith Better Quality of Life Outcomes in DEFUSE 3 The quality of life benefits remainevenafter controlling for stroke severity. P atients who underwent endovascular therapy in the DEFUSE 3 trial have better quality of life outcomes than those who under- went medical therapy alone. For this trial, 182 selected patients with acute ischemic stroke asso- ciated with an initial infarct size <70 mL and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomized to treatment with endovascular therapy plus stand- ard medical therapy or standard medical therapy alone. The trial was terminated early because the primary outcome of modified Rankin Scale score at 90 days clearly favored endovascular therapy. In the present study, the 146 patients from DEFUSE 3 trial who were alive at 90 days were asked to undergo the Neuro-QoL, a measure- ment tool designed to assess quality of life outcomes in adults with neurologic disorders. Among these patients, 128 completed all four Neuro-QoL forms, 8 completed a subset of the forms, and 10 did not complete any of the forms. The findings were presented by Laura Pol- ding, BA, a medical student at Stanford University School of Medicine. Treatment with endovascular therapy was associated with superior quality of life outcomes in all five domains measured by the Neuro- QoL, compared with medical therapy alone: mobility (P < .001), social participation (P < .001), cognition (P = .013), and depression (P = .003). A higher National Institutes of Health Stroke Score at baseline was associated with worse outcomes in mobility, social participation and cognition, older age with worse mobility and depression, and female gender with worse mobility, cognition and depression (multivariable P < .05). The benefit of endovascular therapy in each quality of life domain remained significant even after adjusting for these variables, however. “This study demonstrates that endovascular therapy in late-window patients not only improves disability scores, but also has a major beneficial impact on quality of life,” Ms. Polding told Elsevier’s PracticeUpdate . “Multivariable regression identified increased age as a predictor of worse outcomes in mobility and depression and female sex as a predictor of worse outcomes in all four measured domains. These findings suggest that there is an opportunity to more deeply study the effects of age and sex on social, cognitive, and mental health outcomes in late-window stroke, which could inform selection of more optimal rehabilitative services for patients at risk of worse outcomes.” She highlighted the need for clinical trials of stroke therapy to rou- tinely evaluate quality of life measures. “Analysis from the DEFUSE 3 trial has demonstrated that the modified Rankin Scale is correlated strongly with physical outcomes and moderately with social outcomes, but only weakly with cognition and depression in late-window stroke patients,” she explained. “Mental, cognitive, and social outcomes are all critical measures of patient well-being that should be evaluated as comprehensively as physical outcomes in assessing the benefits of a therapy. Clinical trials should routinely pair measures of physical disability like the modified Rankin Scale with quality of life measure- ment tools to assess a broader range of outcomes important to the individual.” www.practiceupdate.com/c/79800

VOL. 4 • NO. 1 • 2019