Economic Evaluation of Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. METHODS: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0-2) and the extra cost per quality-adjusted life year gained. RESULTS: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, -$16 839 [95% CI, -$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%-22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04-0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. CONCLUSIONS: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: https://www.trialregister.nl/trial/695; Unique identifier: NL695. URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Effect of Heparinized Flush Concentration on Safety and Efficacy During Endovascular Thrombectomy for Acute Ischemic Stroke: Results from the MR CLEAN Registry.

BACKGROUND: Currently, there are no recommendations regarding the use of heparinized flush during endovascular thrombectomy (EVT) for acute ischemic stroke. Periprocedural heparin could, however, affect functional outcome and symptomatic intracranial hemorrhage (sICH). We surveyed protocols on heparin flush concentrations in Dutch EVT centers and assessed its effect on safety and efficacy outcomes. METHODS: Patients registered in the MR CLEAN Registry, from 2014 up to 2017 were included. We collected data on center protocols regarding heparin flush concentrations (IU/L) and grouped patients by their per protocol administered heparin flush concentration. We used a random effects model with random intercepts by EVT center and analyzed endpoints using regression models. Endpoints were sICH, mRS at 90 days, mortality and reperfusion rates. RESULTS: A total of 3157 patients were included of which 45% (6 centers) received no heparin in the flush fluids, 1.8% (1 center) received flush fluids containing 2000 IU/L heparin, 26% (4 centers) received 5000 IU/L, 22% (4 centers) received 10.000 IU/L and 5.6% (1 center) received 25.000 IU/L. Higher heparin concentration was associated with increased sICH (aOR 1.15; 95% CI 1.02-1.29), but not with functional outcome, mortality or reperfusion rates. CONCLUSION: Effect of heparin in flush fluids should not be ignored by clinicians or researchers as higher concentrations may be associated with higher rates of ICH. The observed variation in protocols regarding heparin concentrations between EVT centers should encourage further studies, ideally in a controlled way, resulting in recommendations on heparin use in flush fluids in future guidelines.

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): design and statistical analysis plan of the extended follow-up study.

BACKGROUND: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. METHODS: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. DISCUSSION: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. TRIAL REGISTRATION: NTR1804 . Registered on 7 May 2009; ISRCTN10888758 . Registered on 24 July 2012 (main MR CLEAN trial); NTR5073 . Registered on 26 February 2015 (extended follow-up study).

[Intra-arterial treatment of ischemic stroke--still no evidence but reason for further study]. / Intra-arteriële behandeling van het herseninfarct--nog geen bewijs, maar wel reden voor verder onderzoek.

In 3 recent randomized controlled trials of intra-arterial treatment of acute ischemic stroke - IMS-III, SYNTHESIS and MR RESCUE - intra-arterial treatment increased the proportion of patients with recanalization and the treatment appeared safe. However, the trials did not show an effect on functional recovery, although a substantial effect could not be excluded. The delay between onset of symptoms and treatment was long, and stent retrievers were used in only a few patients. In our view, a rational and ethical approach would now be to treat quickly with IV rtPA and when possible, refer and include in new randomized clinical trials that compare intra-arterial treatment with standard care, such as MR CLEAN or BASICS in the Netherlands.