Complete reperfusion may not offer better outcomes than near-complete reperfusion

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Ching-Jen Chen

Ching-Jen Chen discusses his recent publication in the BMJ entitled, “Is a picture-perfect thrombectomy necessary in acute ischaemic stroke?”

Whether imaging findings translate into outcomes of clinical importance is often a point of contention in imaging-dependent medical specialties such as neurology and neurosurgery. As techniques and technologies for acute ischaemic stroke (AIS) thrombectomy continue to improve, whether some of these advances result in better patient outcomes deserve further investigation. Due to its strong correlation with clinical outcome, recanalisation is often regarded as an important surrogate marker for therapeutic activity in recent AIS thrombectomy trials. As higher rates of recanalisation led to concomitant improvements in patient outcomes, efforts to increase recanalisation rates, through improvements in catheters and thrombectomy techniques, have garnered increasing attention.

Although the American Heart Association (AHA) guidelines defined successful reperfusion as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b or higher, there is mounting evidence to suggest better outcomes in patients who achieved reperfusion beyond the recommended 50% threshold. Consequently, the mTICI 2c grade (90–99% reperfusion) was added to differentiate outcomes of patients with near-complete reperfusion from those with closer to 50% reperfusion. However, whether there is diminishing returns beyond this threshold remains unclear. Should picture-perfect angiographic reperfusion be the goal of AIS thrombectomy?

To answer this question, we compared the outcomes between patients who achieved mTICI 2c and those who achieved mTICI 3 reperfusion in AIS thrombectomy. The study was retrospective in nature, included data from 33 centres, and derived from the Stroke Thrombectomy and Aneurysm Registry (STAR). The study was limited to adult patients with anterior circulation arterial vessel occlusion. The total sample size of the study was 2,442, comprising 519 and 1,923 patients in the mTICI 2c and 3 cohorts, respectively. Rates of good functional outcome (primary outcome; modified Rankin Scale [mRS] score 0–2) at 90 days were similar between patients who achieved mTICI 2c and those who achieved mTICI 3 reperfusion (42.4% vs. 45.1%; odds ratio [OR]=1.118 [0.919–1.360]; p=0.264). Secondary outcomes, including functional and neurological outcomes at discharge and 90 days, intracerebral haemorrhage (ICH), and procedure-related complications were also comparable between the two cohorts.

To control the effects of potential confounders, the two cohorts were matched, and the resulting matched cohorts comprised 191 patients each. Although mTICI 3 reperfusion resulted in an absolute increase in the proportion of patients with the primary outcome of 7.8%, this difference was not significant (39.8% vs. 47.6%; OR=1.377 [0.918–2.066]; p=0.122). This was associated with a lower 90-day mRS score for the matched mTICI 3 cohort in shift analysis (median 3 vs. 3; OR=0.702 [0.493–0.999]; p=0.049). The remainder of the secondary outcomes were comparable between the two matched cohorts. Taken together, complete reperfusion was associated with a 7.8% increase in the rate of functional independence compared to near-complete reperfusion. However, this was not statistically significant and its clinical significance is unknown.

In the study, we identified white race, hyperlipidaemia, and higher Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as predictors of 90-day functional independence. Older age, diabetes mellitus, higher pre-stroke mRS score, higher admission National Institute of Health Stroke Scale (NIHSS) score, longer symptom onset to puncture time, use of combined aspiration and stent retriever technique, higher number of passes, and procedure-related complications were predictors of dependence.

White race and higher ASPECTS remained predictors of 90-day functional independence after adjusting for missing data, while older age, diabetes mellitus, higher pre-stroke mRS score, and higher admission NIHSS score remained predictors of dependence after adjusting for missing data. Reperfusion status (mTICI 2c vs. 3) was not a predictor of functional independence. Finally, we also explored potential interactions between patient subgroups and functional independence. In patients with a pre-stroke mRS score ≥2, those who achieved mTICI 3 had a higher odd of 90-day functional independence (36% vs. 7.7%; adjusted OR [aOR] =15.734 [1.869–132.438], p=0.011; pinteraction=0.014). There was also a greater likelihood of functional independence in patients with a history of stroke who achieved mTICI 3 reperfusion (42.3% vs. 15.4%; aOR=15.594 [1.377–176.595]; p=0.027; pinteraction=0.041). These findings may warrant the pursuit of a more aggressive revascularisation in patients with a history of stroke or pre-stroke disability.

The limitations of our study should be recognised. Most importantly, all imaging data and interpretation were self-reported by the treating neurointerventionalist, and a centralised imaging core laboratory was not available. Furthermore, the revised mTICI grading scale that includes 2c was not universally adopted by all centres, and thus, some mTICI 2c outcomes may have been categorised as grade 3. Consequently, this may have diluted a potential outcome difference between the mTICI 2c and 3 cohorts, thereby effectively increasing the type II error rate. Procedural characteristics that can influence the degree of reperfusion, including difficulties in navigating to the occlusion site and extent of clot burden, may not have been fully captured in our data. The decision to pursue revascularisation of occluded distal branches could not be determined, as the stopping point for each centre and neurointerventionalist is subject to variation. However, it is important to note that core laboratory adjudication is not practical in the real-world setting when determining the threshold of successful reperfusion and procedural stopping point, as this is determined intra-procedurally by the treating neurointerventionalist.

In conclusion, complete reperfusion in patients with anterior circulation AIS who underwent thrombectomy did not appear to confer better outcomes compared to near-complete reperfusion. Patients with pre-stroke disability and those with a history of stroke may have better functional outcomes after complete reperfusion in our exploratory analyses. Therefore, aggressive pursuit of complete angiographic reperfusion as interpreted by the treating neurointerventionalist may not be necessary, and the benchmark of success for emerging AIS thrombectomy techniques and technologies may not need to be picture-perfect.

Ching-Jen Chen is a chief resident at the Department of Neurological Surgery, University of Virginia Health System, Charlottesville, USA.

Disclosures: Ching-Jen Chen reports no disclosures.

 


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