Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis.

Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0-1 and 0-2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29-1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31-2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76-28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%-1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.

Treatment of acute basilar artery occlusion: Systematic review and meta-analysis.

INTRODUCTION: Acute basilar artery occlusion (BAO) results in strokes characterized by poor outcome. Intravenous and intraarterial thrombolysis with rt-PA (IV rt-PA and IA rt-PA, respectively) and mechanical thrombectomy (MT) are the most commonly used techniques to treat BAO, but their efficacy remains unclear. Unlike in previous papers, we compared all three methods of the treatment in a single work, including an update of meta-analysis regarding each of the three therapeutic approaches with recent trials. METHODS: We systematically reviewed all original studies testing the efficacy of any of the three basic methods of BAO treatment dated up to the end of Jan 2017. RESULTS: The final analysis included 31 studies that summarized 1358 patients. These subjects were organized into three therapeutic groups: IV rt-PA, IA rt-PA±IV rt-PA, MT±IV rt-PA±IA rt-PA. The weighted pooled estimates of a favorable outcome (mRS 0-2) were 32.57% (95% CI 16.44-51.03%/I2=67.5%, p=0.0795) in the first group, 22.56% (95% CI 16.85-28.79%/I2=52.1%, p=0.027) in the second group, and 37.04% (95% CI 32.27-41.92%/I2=32%, p=0.0895) in the third group. The Q-test subgroup analysis revealed the statistical superiority of MT±IV rt-PA±IA rt-PA over IA rt-PA±IV rt-PA (mRS 0-2: p=0.0003, mRS 6: p=0.0010) and over any rt-PA administration (either IV rt-PA or IA rt-PA±IV rt-PA) (mRS 0-2: p=0.0006, mRS 6: p=0.0056). CONCLUSIONS: Current data on the effects of the three basic approaches of the treatment of BAO are insufficient to generate high-class EBM guidelines. MT seems to be the most effective method of the treatment of acute BAO. The efficacy of IV or IA thrombolytic therapy in this indication remains unclear.