Ramanathan, Kadirvel

Abstract Background and aims Intravenous thrombolysis (IVT) is the most common acute ischemic stroke (AIS) treatment. This study compared the efficacy and safety of different IVT agents to determine the optimal option for AIS management. Methods A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Cochrane CENTRAL until 23 March 2025. Randomized controlled trials (RCTs) on alteplase (tPA), tenecteplase (TNK), reteplase, and recombinant human pro-urokinase (rhPro-UK) of any dose in AIS were included. A frequentist network meta-analysis was conducted using R software to pool risk ratios (RRs) with 95% confidence intervals (CIs). Results Twenty-one RCTs (10,852 patients) were included. Compared with tPA 0.9 mg/kg, tPA 0.6 mg/kg showed a lower risk of symptomatic intracranial hemorrhage (RR, 95% CI: 0.48 [0.27–0.86]), whereas TNK 0.4 mg/kg showed a higher risk (RR, 95% CI: 1.88 [1.06–3.35]). Reteplase 18 + 18 mg (RR, 95% CI: 1.13 [1.05–1.21]) and TNK 0.25 mg/kg (RR, 95% CI: 1.05 [1.01–1.10]) were associated with higher rates of excellent functional outcome at 90 days (mRS 0–1) compared with tPA 0.9 mg/kg. No significant differences were observed among interventions in 90-day mortality and favorable function outcomes (mRS 0–2), or serious adverse events. Conclusions Thrombolytic efficacy and safety in AIS appear to be dose dependent. A lower tPA dose (0.6 mg/kg) improved safety; reteplase 18 + 18 mg and TNK 0.25 mg/kg favored functional recovery, whereas a higher TNK dose increased sICH risk, underscoring the importance of dose optimization in IVT selection. Conflict of interest Haneen Sabet: nothing to disclose, Moaz Elsayed Abouelmagd: nothing to disclose, Abdelrahman Shata: nothing to disclose, Mohamed El-Moslemani: nothing to disclose, Diana Kadi: nothing to disclose, Dina Essam Abo-elnour: nothing to disclose, Abdallah Abbas: nothing to disclose, Ramanathan Kadirvel: nothing to disclose, Sherief Ghozy: nothing to disclose Figure 1 - belongs to Results

Background Mechanical thrombectomy (MT) has become the standard of care for stroke patients. The majority of the clinical trials and publications analyzing the outcomes related to the procedures report interventional performance by experienced practitioners. However, few of them individualize their preliminary metrics according to the operator's experience. Objective To summarize the literature and report safety and efficacy outcomes following MT procedures and correlate them with the operator's experience. Primary outcomes were successful recanalization, defined as modified thrombolysis in cerebral infarction greater or equal to 2b or 3, duration of the procedure measured in minutes, and serious adverse event. Methods This systematic review was performed according to the PRISMA guidelines. The PubMed, Embase, and Cochrane databases were utilized. Results There were six studies comprising 9348 patients (mean age 69.8 years; 51.2% males), and 9361 MT procedures were included. Each publication used for this review used a different experience definition to report their data. Higher interventionists’ experience demonstrated a positive relationship with the possibility of successful recanalization and an inverse relationship with the duration needed for the operation in almost all of the included studies. As for the complications, none of the authors reported a statistically significant risk reduction of an adverse event, except Olthuis et al. correlating increasing training with lower odds of stroke progression. Conclusions A higher experience level is associated with better recanalization rates and shorter procedural duration in MT operations. Further studies are warranted to define the minimum required level of experience for operational autonomy.