Tapan Mehta, MBBS, MPH
Mechanical thrombectomy (MT) has been proven to be superior to intravenous thrombolysis (IVT) in proximal large vessel anterior circulation strokes (LVO); however, the standard of care is still to provide IVT to eligible patients before MT. Rigorous data is lacking, however; the need for IVT in the patients with LVO who are eligible for MT is being questioned.
The article by Mistry et al is an important meta-analysis of 13 studies that explored the differences in clinical outcomes (mortality, morbidity with mRS (Modified Rankin Scale; 0-2 defined as good outcome), symptomatic intracranial hemorrhagic (sICH), and successful recanalization rates for patients receiving MT+IVT versus only MT (MT – IVT)). This meta-analysis included studies from 2006 to 2016. Separate sub-group analyses were performed for randomized clinical trials (RCT) and non-randomized studies each. Sub-group analysis for the RCT group demonstrated higher, but nonsignificant, Odds Ratio (OR) for good functional outcomes (OR, 1.28 [95% confidence interval (CI), 0.93–1.75], P=0.12) and a significantly lower OR for mortality (OR, 0.56 [95% CI, 0.36–0.86], P=0.007) in MT+IVT compared with MT−IVT patients. The sub-group analysis of patients in nonrandomized studies demonstrated a strong trend with quantitatively similar OR of 1.31 (95% CI, 0.99–1.73, p=0.06) for good functional outcomes and OR 0.76 (95% CI, 0.56–1.03, p=0.08) in MT+IVT compared to MT−IVT patients.
Overall, MT+IVT patients demonstrated higher odds of having good functional outcomes and lower mortality than MT−IVT patients (mRS 0–2: OR, 1.27 [95% CI, 1.05– 1.55], P=0.02); mortality: OR, 0.71 [95% CI, 0.55–0.91], P=0.006. Similar rates of sICH were observed in MT+IVT and MT−IVT patients. The number needed to treat for 1 additional individual to incur a mRS of 0 to 2 was calculated to be 17 (95% CI, 10–83). MT+IVT demonstrated significantly higher odds of achieving a successful recanalization than MT−IVT patients (OR, 1.46 [95% CI, 1.09–1.96], P=0.01), and also showed significantly higher odds of achieving a successful recanalization within 2 passes of mechanical thrombectomy device (OR, 2.06 [95% CI, 1.37–3.10], P=0.0005) compared with MT−IVT patients.
Outcome heterogeneity due to a difference in symptom onset to groin puncture time (a very important variable that determines the interpretation of these study results) was examined by a meta-regression. This analysis did not show any significant correlation between outcomes and symptom to groin puncture time between MT+IVT and MT-IVT groups (slope=−0.5×10−4; P=0.95; see Figure 3 from the article below).
Figure 3: Meta-regression of differences in time to treatment and log of odds ratios of good functional outcomes in studies included in the meta-analysis.
One of the major limitations of the study is that MT+IVT and MT−IVT groups are largely classified based on eligibility for intravenous thrombolysis. Similarly, a significant number of patients classified in the MT-IVT group could have altered coagulation profile with inherent higher risk of bleeding. The study did not show a significant difference for sICH in MT+IVT versus MT-IVT group. This could be due to a classification bias.
In conclusion, the MT+ IVT group had better functional outcomes, lower mortality, and a higher rate of successful recanalization, and required a lower number of device passes compared to MT-IVT patients. There was no significant difference in symptom to groin puncture time among these two groups. In addition to supporting the current guidelines, this study suggests that extreme caution is required in the study design of the clinical trials that examine a possibility of bypassing the need for intravenous thrombolysis in patients with LVO qualifying for endovascular therapy.
