With multiple large clinical trials currently underway to assess thrombectomy treatments in patients with medium vessel occlusion (MeVO) stroke, Johanna Ospel (Calgary, Canada) takes a look at the possibility of endovascular therapy (EVT) becoming the standard of care for these cases further down the line.

Since 2015, EVT has become the standard of care for acute ischaemic stroke patients with large vessel occlusions (LVOs) meeting certain eligibility criteria.¹ In the following years, treatment criteria have been expanded to the late time window, patients with large baseline infarcts and basilar occlusions. Life has become much busier for neurointerventionists and the majority of LVO patients, including those with proximal M2 occlusions, who are admitted to a hospital are nowadays treated with EVT in many countries.

Current MeVO treatments

But, what happens with smaller occlusions, such as distal M2 or M3 occlusions? Treatment of these so-called MeVOs is much more variable—while some centres follow very aggressive treatment regimens and routinely attempt EVT in MeVO patients, others pursue medical treatment only, especially when staff and financial resources are limited.

There are good arguments for both approaches. MeVOs are smaller, more likely to recanalise with intravenous thrombolysis (IVT) and the procedural complication risk is expected to be higher; clearly, there is less to gain and more to lose compared to LVOs.

On the other hand, data from prospective cohort studies have clearly shown that the prognosis of medically treated MeVO stroke is poor, with one in three patients not being functionally independent at 90 days and one in 11 patients dying within three months after their stroke.²

Ongoing EVT trials

Clearly, high-level evidence from randomised trials is necessary to standardise management of MeVO stroke and offer the best possible treatment to our MeVO patients. To do so, several randomised MeVO trials have been initiated: ESCAPE-MeVO in Canada, DISTAL in Switzerland, DISCOUNT in France and DISTALS in the USA.

Except for DISTALS, which uses successful reperfusion as a primary outcome, all the other trials aim to demonstrate clinical benefit of MeVO EVT on the modified Rankin scale (mRS). The choice of the primary outcome is a tricky one when it comes to MeVO stroke, as reperfusion success is an angiographic outcome that is not immediately meaningful to patients, and therefore not sufficient to change guidelines.

The most commonly used and widely accepted clinical outcome is the mRS—a relatively crude measurement scale, which is used as the primary outcome in the other MeVO trials. But, since MeVO patients are less severely affected than LVO patients, they generally do well, and demonstrating benefit on the mRS could be challenging because the scale may lack the necessary granularity to detect the subtle deficits caused by MeVO stroke.

Will randomised studies give us the answer?

Randomised trial results are not necessarily generalisable to the ‘real-world setting’ because of the strict trial eligibility criteria, since EVT-capable hospitals participating in such trials may differ from those who do not, and because of the Hawthorne effect whereby physicians and other hospital staff are aware that a given MeVO patient is part of a trial and may treat these patients differently from non-trial patients.

Even if the currently ongoing MeVO trials end up showing benefit of MeVO EVT, not all MeVO patients will benefit from EVT performed by any neurointerventionist in any hospital. It may well be that less experienced neurointerventionists should be more cautious and opt for medical treatment in more distal MeVOs until they have gained the skillset and experience to safely treat these small occlusions.

On the other hand, if the MeVO trials fail to show EVT’s benefit, this does not mean that no benefit exists. The sample size may be too small or, perhaps, the right endovascular tools do not exist yet. Over time, as more and more MeVOs get treated, smaller and more flexible catheters and stent retrievers will be developed, which will make MeVO EVT safer and shift the risk-benefit balance.

So, will MeVO EVT become the standard of care after all? Only time will tell. Irrespective of what trial results will be, sound clinical reasoning and a careful evaluation of the potential treatment risks and benefits will remain essential in every patient.

References:

1. Goyal M, Menon B K, van Zwam W H, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016; 387(10029): 1723–31. DOI: 10.1016/S0140-6736(16)00163-X.
2. Ospel J M, Menon B K, Demchuk A M, et al. Clinical Course of Acute Ischemic Stroke due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment. Stroke. 2020; 51: 3232–40. DOI: 10.1161/STROKEAHA.120.030227.