Endovascular Treatment Has No Added Benefit on Cerebral Venous Thrombosis Outcomes


Coutinho et al. noted that future studies that feature a larger population will help to better determine recovery rates after endovascular treatment.

Jonathon M. Coutinho, MD, PhD

Jonathon M. Coutinho, MD, PhD

Results from the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) study (NCT01204333) revealed that treating cerebral venous thrombosis (CVT) with endovascular treatment (EVT) plus standard care does not improve functional outcomes compared with standard of care alone.

Research conducted by Jonathon M. Coutinho, MD, PhD, department of neurology, Amsterdam University Medical Centers, and colleagues showed that 22 patients (67%) who received EVT with standard medical care, known as the intervention group, had a modified Rankin Scale (mRS) score of 0 to 1, compared with 23 control patients (68%) at 12-month follow-up (relative risk ratio, 0.99; 95% CI, 0.71—1.38).

Mortality was not statistically significantly higher in the EVT group (12% [n = 4] vs 3% [n = 1]; P = .20) and the frequency of symptomatic intracerebral hemorrhage was not statistically lower as well (3% [n = 1] vs 9% [n = 3]; P = .61).

TO-ACT was a multicenter, open-label, blinded end point clinical trial conducted in 8 hospitals across 3 countries that featured 67 patients who were randomized 1:1 to the intervention group (n = 33) and the control group (n = 34). Demographically, the intervention group had a higher overall age than the control group (median age, 43 [interquartile range (IQR), 33—50] years vs 38 [IQR, 23–48] years) and included fewer women as well (23 women [70%] vs 27 women [79%]).

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At baseline, those in the EVT group had a median National Institutes of Health Stroke Scale score of 12 (IQR, 7—20), compared with 12 (IQR, 5–20) in the standard care group. Patients included in the study began follow-up in March 2012 and completed the trial in December of 2017. Adult patients with radiologically confirmed CVT and who had at least 1 risk factor for a poor outcome, such as mental status disorder, coma state, intracerebral hemorrhage, or thrombosis of the deep venous system met criteria and were included.

The primary outcome of the study was a favorable clinical outcome, measured as a score between 0—1 on mRS at 12 months following randomization. Additional secondary outcomes included recanalization rate of cerebral venous system, all cause mortality, required surgical intervention in relation to CVT, and major extracranial and symptomatic hemorrhagic complications.

The main objective of the TO-ACT trial is to determine if EVT improves functional outcome in patients with a severe form of CVT. In previous studies, EVT has shown different variation of effectiveness as a stroke treatment. A study published in May 2019 showed that the treatment method demonstrated similar rates of successful clinical and procedural outcomes in patients with and without prestrike disability.2

EVT was shown to have similar outcomes compared with EVT and intravenous thrombolysis (IVT) in a study published earlier this March on patients with large vessel occlusion. In the study, favorable outcomes at 90 days was found in 60 of the 101 patients (59.4%) treated with EVT, compared to 59 of 103 patients (57.3%) in the bridging therapy group (odds ratio [OR], 1.09; 95% CI, 0.63 to 1.90; the lower boundary exceeded the noninferiority margin of 0.74; P = 0.18 for non-inferiority).3

TO-ACT was prompted from previous studies that were uncontrolled, and did not fully evaluate the safety and efficacy of EVT in patients with CVT. Coutinho and colleagues concluded, “The neutral results of the TO-ACT trial should not be interpreted as definitive proof that EVT is ineffective in CVT. Although the point estimate of the primary end point in the trial did not point toward a beneficial effect of EVT in CVT (RR ratio, 0.99), the large width of the 95% CI (0.71—1.38) indicated that a clinically meaningful treatment effect cannot be excluded.”

In the conclusions section, researchers noted that this was the first randomized clinical trial on the efficacy and safety of EVT in patients with CVT and at high risk of bad outcome but there were limitations that came with it. The study authors performed magnetic resonance imaging between months 6 to 12, leaving questions on direct impact of EVT on early recanalization. Additionally, because of the sample size and limited number of outcome events, the researchers could not adjust the primary analysis for prognostic variables.

Future studies using methods of patient selection and EVT techniques may identify better recovery rates after EVT for patients with severe CVT and should thus not be excluded.


1. Coutinho JM, Zuurbier SM, Bousser MG, Effect of endovascular treatment with medical management vs standard care of severe cerebral venous thrombosis. JAMA Neurol. Published online May 18, 2020. doi: 10.1001/jamaneurol.2020.1022

2. Salwi S, Mistry A, Espaillat K, et al. Comparative Outcome Analysis of Endovascular Acute Ischemic Stroke Treatment in Patients With and Without Pre-stroke Disability. Presented at: 2019 American Academy of Neurology Annual Meeting. May 4-10, 2019; Philadelphia, PA. Abstract: S57.009.

3. Matsumaru Y, Takeuchi M, Morimoto M, et al. The randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion (SKIP study). Presented at: 2020 International Stroke Conference. February 19-21, 2020; Los Angeles, CA. Abstract LB18.

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