There are likely to be minimal differences in clinical outcomes between acute stroke patients presenting directly to endovascular treatment centres who undergo mechanical thrombectomy alone, and those who receive intravenous thrombolysis (IVT) plus thrombectomy. That is according to a meta-analysis examining six randomised controlled trials (RCTs) and more than 2,300 patients, which is now published in The Lancet, and ultimately found that non-inferiority of thrombectomy alone could not be established in these patients.
Outlining the latest data from the Improving Reperfusion strategies in Ischemic Stroke (IRIS) collaboration, Charles Majoie, Yvo Roos (both Amsterdam University Medical Centers [UMC], Amsterdam, The Netherlands) et al initially note that IVT is recommended before endovascular thrombectomy treatment, but its value “has been questioned” in patients who are admitted directly to centres capable of both treatments.
“Existing RCTs have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive,” they add—also stating that the IRIS collaboration has been formed to assess the non-inferiority of endovascular thrombectomy alone, as compared to IVT plus thrombectomy.
To this end, Majoie, Roos et al conducted a systematic review and individual participant data meta-analysis, searching PubMed and MEDLINE for relevant articles published from database inception to 9 March 2023. They ultimately identified six RCTs on the topic of interest—DIRECT-MT, DEVT, SKIP, MR CLEAN-NO IV, SWIFT DIRECT and DIRECT-SAFE—with the respective authors of each agreeing to take part, and individual participant data from all the trials being provided and collated centrally.
The researchers’ primary outcome was the 90-day modified Rankin scale (mRS) score, they detail. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0.82 for the 95% confidence interval (CI) around the adjusted common odds ratio (OR) for a shift towards improved functional independence outcomes with ordinal regression. The researchers report using mixed-effects models for all their analyses.
The six RCTs deemed eligible for analysis provided data on 2,313 patients—1,153 of whom were randomly assigned to receive thrombectomy alone and 1,160 of whom were randomly assigned to receive IVT plus thrombectomy.
“The risk of bias of the included studies was low to moderate,” Majoie, Roos et al relay. “Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution.”
The researchers found a median 90-day mRS score of 3 (interquartile range [IQR] 1–5) in the thrombectomy-only cohort of patients and 2 (IQR 1–4) in patients who received IVT plus thrombectomy, with an adjusted common OR of 0.89 (95% CI 0.76–1.04). In addition, any intracranial haemorrhage (ICH) occurred less frequently with thrombectomy alone as compared to IVT plus thrombectomy (adjusted common OR 0.82, 95% CI 0.68–0.99), while symptomatic ICH and mortality rates did not differ significantly between the two patient cohorts.
After concluding that their study did not establish non-inferiority of thrombectomy alone versus IVT plus thrombectomy in patients presenting directly at endovascular treatment centres, Majoie, Roos et al deliver the following message: “Further research could focus on cost-effectiveness analysis, and on individualised decisions when patient characteristics, medication shortages or delays are expected to offset a potential benefit of administering IVT before endovascular treatment.”
As the researchers were unable to exclude the possibility that omitting IVT could lead to worse outcomes, further investigations are now planned—for example, via dedicated substudies—to explore the impact individual patient differences may have on the efficacy of thrombolysis.
“It is crucial to recognise that the actual benefit of additional IVT is likely to be small and may vary depending on factors, such as the time from stroke onset, in stroke patients admitted directly to endovascular treatment centres,” co-lead author Majoie is quoted as saying in an Amsterdam UMC press release. “It is imperative that IVT does not cause any delays, restrict access to, or take precedence over endovascular treatment, considering the limited and uncertain effect it has compared to the large impact of endovascular treatment itself.”