Stroke

DIRECT-MT: Should stroke patients selected for mechanical thrombectomy also receive intravenous thrombolysis?

The first randomized controlled trial investigating treatment with thrombolysis before mechanical thrombectomy was recently published.

After seven randomized controlled trials published in 2014-16 showed that mechanical thrombectomy was an effective treatment for anterior circulation large vessel occlusion stroke, the question remained whether patients should still receive intravenous thrombolysis before treatment with mechanical thrombectomy. Current ESO and AHA guidelines recommend treatment with both intravenous thrombolysis and mechanical thrombectomy whenever indicated.  

The DIRECT-MT study is the first randomized controlled trial investigating whether co-treatment with intravenous thrombolysis is beneficial for patients selected for mechanical thrombectomy. 656 patients in 41 Chinese centres with anterior circulation large vessel occlusion eligible for both mechanical thrombectomy and intravenous thrombolysis were included and randomized 1:1 do receive mechanical thrombectomy with or without pre-treatment with intravenous Alteplase. Median age was 69, about 43% of patients were female, median NIHSS at admission was 17, the two treatment groups were well matched regarding baseline characteristics.

The study found no significant differences in the main outcome variables (modified Rankin Scale at three months, NIHSS after 24 hours and discharge, Barthel Index). Furthermore, rates of both symptomatic and asymptomatic haemorrhage were similar. Thrombectomy alone was shown to be non-inferior compared to thrombectomy plus thrombolysis regarding the primary outcome variable, modified Rankin Scale after three months, albeit using a rather generous non-inferiority margin of 20%.

However, patients in the thrombolysis group more frequently had successful reperfusion on digital subtraction angiography both before and after mechanical thrombectomy (7.0 vs. 2.4% before, 84.5% vs. 79.4% after mechanical thrombectomy), but this did not lead to differences in functional outcome.

Some limitations of the study need to be noted. Patients were only included in intervention centres, the time to symptom onset to start of Alteplase was relatively long (median 184 minutes) and the time from initiation of Alteplase to groin puncture was quite short (median 29 minutes). Tenecteplase was shown to be superior to Alteplase for intravenous thrombolysis before mechanical thrombectomy in the EXTEND-IA-TNK trial, but was not used in this study. Overall, the number of patients with favourable outcome (mRS 0-2 at three months post-stroke) was rather low (36%) compared to most other thrombectomy trials, the proportion of ICA occlusions (35%) higher than previously observed. Furthermore, the health system in China has some characteristics not shared by the majority of European countries and there are known ethnic differences in stroke, potentially limiting generalizability.

This means that the trial’s results cannot easily be translated to different settings, especially to patients with longer times between initiation of thrombolysis and groin puncture for thrombectomy (including patients transferred from primary stroke centres to intervention centres in a drip-and-ship model) and European health care systems. Therefore, it seems to be appropriate to follow current guidelines recommending intravenous thrombolysis for all eligible patients before thrombectomy until additional data are available. Other randomized controlled trials investigating very similar research questions are currently recruiting and expected to clarify some of these open questions.

 

Key points:

  • DIRECT-MT was a randomized controlled trial comparing mechanical thrombectomy with pre-treatment with intravenous thrombolysis with mechanical thrombectomy alone
  • Among the main outcome variables, no differences could be shown between the two treatment groups.
  • However, patients in the thrombectomy with thrombolysis group more frequently had successful reperfusion before and after mechanical thrombectomy
  • Limitations include that patients were only included in thrombectomy centres, short times between initiation of thrombolysis to groin puncture and specifics of the Chinese health system
  • Therefore, these results cannot easily be translated to patients treated in drip-and-ship models and different health care systems.

 

References:

Yang P, Zhang Y, Zhang L, et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020 May 6 (Epub). https://www.ncbi.nlm.nih.gov/pubmed/32374959

Albers G. Thrombolysis before Thrombectomy — To Be or DIRECT-MT? N Engl J Med. 2020 May 6 (Epub). https://www.ncbi.nlm.nih.gov/pubmed/32374954