Sergey V. Ivanov

The approach to reperfusion therapy for acute ischemic stroke (AIS) in cases of basilar artery occlusion (BAO) remains a matter of debate.    Objective:  to assess the safety and efficacy of Fortelyzin in patients with BAO in real-world clinical practice, based on data from the FORPI registry.   Material and methods.  The FORPI registry is an open-label, prospective, non-interventional observational study of Fortelyzin in patients with ischaemic stroke. An analysis was conducted of the safety and efficacy of Fortelyzin in a group of patients with basilar artery occlusion who underwent intravenous thrombolytic therapy (IVT) and bridging therapy. The safety endpoint was the incidence of symptomatic intracranial haemorrhage (SICH) as defined by ECASS III and SITS-MOST, as well as all-cause mortality at 90 days. The efficacy endpoint was defined as good functional recovery, defined as a score of 0–2 on the modified Rankin Scale (MRS) at 90 days.    Results. This analysis included 1910 patients who underwent IVT and 53 patients who underwent bridging therapy. The median National Institutes of Health Stroke Scale (NIHSS) scores at admission were 9 and 12 points, respectively (p = 0.01). SICH incidence (ECASS III criteria) was significantly higher in the bridging therapy group compared to IVT group (6 % vs 1 %, p = 0.01). All-cause mortality at day 90 did not differ significantly between the groups (9 % and 7 %, respectively, p = 0.52). Good functional recovery at day 90 was achieved by 69 % of patients in the IVT group and 60 % of patients in the bridging therapy group (p = 0.31).    Conclusion. The use of Fortelyzin in AIS patients with BAO may be considered an effective and safe form of reperfusion therapy, as well as a component of bridging therapy aimed at increasing the number of favorable functional outcomes.

The question of whether intravenous thrombolytic therapy (ITT) is appropriate for patients with a minor stroke (NIHSS score < 5) remains a matter of debate. Fortelysin is a thrombolytic agent used to treat ischemic stroke.    Objective:  to assess the safety and efficacy of Fortelyzin in patients who have suffered a minor stroke in real-world clinical practice, based on data from a subanalysis of the FORPI registry.    Material and methods.  The FORPI registry is an open-label, prospective, non-interventional, observational study of Fortelyzin in patients with acute ischemic stroke. We analyzed the safety and efficacy of Fortelyzin in a group of patients with minor stroke characterized by an NIHSS < 5. Safety outcomes were the number of symptomatic intracranial hemorrhage (sICH) according to ECASS III and SITS-MOST definitions, as well as all-cause mortality at day 90. The efficacy outcome was a functional independence, defined by modified Rankin scale (mRS) score of 0–2 points at day 90.    Results.  The analysis included 836 patients with an NIHSS < 5 points. The median age was 64 [56; 72] years, and the median NIHSS score at admission was 4 [3; 4] points. SICH according to ECASS III definition was observed in three patients of 836 (0.4 %), and according to SITS-MOST definition, in four patients of 836 (0.5 %). All-cause mortality at day 90 was 2.2 % (18/836). The proportion of patients with functional independence (mSR of 0–2 points) at day 90 reached in 88 % (737/836) of patients.    Conclusion. The FORPI registry provides compelling evidence that early intensive rehabilitation using Fortelyzin is characterised by a high level of safety and efficacy in patients who have suffered a minor stroke.

Objective. The aim of this study was to evaluate the safety and efficacy of Fortelyzin in patients ≥80 years with ischemic stroke (IS) in real-world clinical practice using data from the FORPI registry. Material and Methods. Fortelyzin (INN/chemical name — a recombinant protein containing the amino acid sequence of staphylokinase, SuperGene LLC, Moscow, Russia) is a thrombolytic used for acute IS treatment within the first 4.5 hours of symptom onset. The FORPI registry is an open-label, prospective, non-interventional, observational study of Fortelyzin in patients with IS. We analyzed the safety and efficacy outcomes in patients ≥80 years compared with patients <80 years. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) according to ECASS III and SITS-MOST definitions, as well as all-cause mortality on day 90. The efficacy outcome was a good functional recovery, defined by an mRS score of 0—2 on day 90. Results. 2649 (15%) patients were ≥80 years, and 14 987 (85%) patients were <80 years. The median age in the group of patients ≥80 years was 83 (82—86) years. Patients ≥80 years were characterized by a more complicated medical history and a higher median of NIHSS and mRS score. The sICH rate according to ECASS III definition in patients ≥80 years old was 4.0%, in patients <80 years old — 1.7% (OR 2.42 (1.90—3.07), p<0.001), according to SITS-MOST definition — 3.2% and 1.6%, respectively (OR 2.03 (1.56—2.61), p<0.001); in-hospital all-cause mortality was 17% and 7% (OR 2.76 (2.44—3.11, p<0.001), all-cause mortality on day 90 was 19% and 7% (OR 3.00 (2.67—3.37, p<0.001), respectively. Good functional recovery (mRS 0—2 score) on day 90 was achieved in 43% of patients ≥80 years and 64% in patients <80 years of age (OR 0.42 (0.38—0.46, p<0.001)). Conclusion. FORPI study showed that although the risk of sICH with Fortelyzin is higher in patients ≥80 years than in patients <80 years, it remains low, suggesting that thrombolytic therapy is safe and necessary in these patients.

Objective. To evaluate the safety and efficacy of Fortelyzin during bridging therapy (thrombolysis followed by thrombectomy) in real-world clinical practice using data from the FORPI registry. Material and methods. The FORPI registry is an open-label, prospective, non-interventional observational study of Fortelyzin in patients with acute ischemic stroke. In this article we analyzed the safety and efficacy of Fortelyzin in patients undergoing thrombolysis followed by thrombectomy. The safety outcomes were the rate of symptomatic intracranial hemorrhage (sICH) according to ECASS III and SITS-MOST definitions, as well as all-cause mortality on day 90. The efficacy outcome was a good functional recovery, defined by mRS score of 0—2 on day 90. Results. The analysis included 1116 patients undergoing thrombolysis followed by thrombectomy who were enrolled in a registry at 120 medical cites in 55 regions of the Russian Federation. The median patient age was 69 (61—77) years. The median NIHSS score at admission was 15 (12—19) points. The sICH rate according to ECASS III was 13% (144/1116), and according to SITS-MOST was 9% (98/1116). In hospital mortality rate was 27% (301/1116 patients). All-cause mortality on day 90 was 29% (322/1116 patients). Good functional outcome (mRS 0—2) on day 90 was achieved in 38% (422/1116) of patients. Conclusion. This study demonstrates the safety and efficacy of Fortelizin in bridging therapy of acute ischemic stroke in real-world clinical practice.

   Objective:  to evaluate the prognostic value of the THRIVE scale in patients aged 60 years and older with ischemic stroke (IS) after intravenous thrombolysis with Fortelyzin® (INN/chemical name – recombinant protein containing the amino acid sequence of staphylokinase; SuperGene LLC, Russia) compared to alteplase, based on a retrospective analysis of the results of the FRIDA randomised clinical trial.    Material and methods. Patients (n = 336) were randomly assigned to either the Fortelyzin group (n = 168) or the alteplase group (n = 168). There were 124 patients (74 %) aged 60 years or older in the Fortelyzin group and 123 patients (73 %) in the alteplase group, and these patients were included in the analysis presented. Patients aged 60 years and older were also divided into two groups according to their modified Rankin scale (mRS) score on day 90: a group with a good functional outcome (mRS 0–2) and a group with an unfavourable functional outcome (mRS 3–6). The THRIVE scale was used to predict outcomes after treatment with Fortelyzin or alteplase. AUC values were then calculated. AUC ROC values were compared using the DeLong criterion.    Results. For all-cause mortality at day 90, the predicted AUC value on the THRIVE scale was 0.8 (0.71–0.9) in the Fortelyzin group and 0.76 (0.66–0.87) in the alteplase group (p = 0.57). For adverse functional outcomes, the AUC value was 0.73 (0.64–0.82) in the Fortelyzin group and 0.79 (0.71–0.87) in the alteplase group (p = 0.36).    Conclusion. The study confirmed the high predictive value of the THRIVE scale for predicting mortality and adverse outcomes in patients aged 60 years and older with IS after treatment with Fortelyzin and alteplase.

Objective. To evaluate the safety and efficacy of Fortelyzin thrombolytic drug (non-immunogenic staphylokinase) in AIS patients in an «extended» therapeutic window from 4.5 to 24 h from symptoms’ onset based on data from the FORPI registry. Material and methods. Functional outcomes and the risk of intracranial hemorrhage after thrombolytic therapy (TLT) for acute ischemic stroke (AIS) are known to be directly dependent on the treatment time initiation. Although the most safe and effective time for TLT is the first 4.5 h from symptoms’ onset, a significant proportion of patients are hospitalized beyond this time window. The objective of this study is The FORPI registry is an open-label, prospective, non-interventional observational study of Fortelyzin in AIS patients in real-world clinical practice. A comparative analysis of safety and efficacy outcomes was conducted in groups of patients who received TLT in the first 4.5 h after symptom onset and beyond 4.5 h time window. The safety endpoints were the rate of symptomatic intracranial hemorrhage (sICH) according to ECASS III and SITS-MOST criteria, as well as all-cause mortality at day 90. The efficacy endpoint was good functional recovery, defined by a modified Rankin Scale (mRS) of 0—2 score at day 90. Results. The analysis included 17.636 patients with TLT performed in the first 4.5 h after symptom onset and 358 patients with TLT performed beyond 4.5 h time window (up to 24 hours). In the group of patients with TLT performed in the interval of 4.5—24 hours, there were statistically significantly fewer people over 80 years old (8% vs 16%, p=0.001), and a lower median age (66 vs 68 years, p=0.002) compared with the group of TLT within 4.5 hours. The NIHSS median was slightly higher in the group of patients with TLT performed beyond 4.5 h time window (11 (8—16) vs 11 (8—15), p=0.036). The incidence of sICH (ECASS III) within 4.5 h was 2% compared with 2.5% beyond 4.5 h time window (p=0.454). All-cause mortality at 90 days in the main population was 9%, which is comparable with the mortality rate in the 4.5—24 h group — 7% (p=0.160). Good functional recovery (mSR 0—2) at day 90 was achieved in 61% of patients in the group who received TLT within 4.5 h, compared with 65% of patients who received TLT beyond 4.5 h time window (p=0.227). Conclusion. FORPI registry demonstrates similar data on the safety and efficacy of TLT with Fortelyzin in AIS patients both within 4.5 hours and beyond 4.5 hours from symptoms’ onset.

BACKGROUND: The non-immunogenic staphylokinase is a recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and fibrin selectivity approved in Russia for the acute ischemic stroke (AIS) thrombolytic therapy within 4.5 hours after symptom onset. We evaluated safety and efficacy outcomes of the non-immunogenic staphylokinase usage in patients with AIS in the Fortelyzin Population Investigation registry. METHODS: Between March 2021 and October 2024, patients with AIS treated with the non-immunogenic staphylokinase were enrolled in the prospective, open-label, internet-based, monitored, observational Fortelyzin Population Investigation registry. Demographics, risk factors, baseline stroke severity (defined by National Institutes of Health Stroke Scale), and onset to treatment time were recorded. Safety outcomes included symptomatic intracerebral hemorrhage (according to the ECASS III [European Cooperative Acute Stroke Study III] and SITS-MOST [Safe Implementation of Thrombolysis in Stroke—Monitoring Study] criteria) within 36 hours and all-cause mortality on day 90. Efficacy outcome was evaluated by functional independence using of modified Rankin Scale score of 0 to 2 on day 90. RESULTS: A total of 17 636 patients with AIS were treated with the non-immunogenic staphylokinase in 329 centers participated in the Fortelyzin Population Investigation registry during the study period (median age 68 [60–75]; 56% male; median baseline National Institutes of Health Stroke Scale score, 11 [8–16] points; median onset to treatment time, 2.4 hours [1.8–3.1]). The rate of symptomatic intracerebral hemorrhage according to the ECASS III criteria was 2% (356/17 636; 1.8–2.2), to the SITS-MOST criteria, 2% (330/17 636; 1.8–2.1). All-cause mortality on day 90 was 9% (1588/17 636; 8.6–9.4). The number of patients with a modified Rankin Scale score of 0 to 2 on day 90 was 61% (10 799/17 636; 60.5–61.9). These safety and efficacy outcomes were comparable with FRIDA (Fortelyzin Randomized Investigation Compared With Alteplase) randomized clinical trial results. CONCLUSIONS: The presented data suggest that intravenous thrombolysis with the non-immunogenic staphylokinase is safe and effective in routine clinical practice when used within 4.5 hours of AIS symptoms onset. These findings should encourage the wider usage of thrombolytic therapy with the non-immunogenic staphylokinase for suitable patients. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06707987.

Objective. To evaluate safety and efficacy outcomes of Fortelyzin in AIS patients in the FORPI (Fortelyzin Population Investigation) registry. Material and methods. Between March 2021 and October 2024 AIS patients treated with Fortelyzin were enrolled in prospective, open, monitored, observational FORPI registry. Demographics, risk factors, baseline stroke severity, defined by National Institutes of Health Stroke Scale (NIHSS), and onset to treatment time were recorded. Safety outcomes included symptomatic intracerebral haemorrhage (ICH) (according to the ECASS III and SITS-MOST criteria) within 36 h and all-cause mortality on day 90. Efficacy outcome was evaluated as a functional independence defined by modified Rankin scale (mRS score of 0—2) on day 90. Results. A total of 17 636 AIS patients were treated with Fortelyzin in 329 centres participated in the FORPI registry during the study period (median age 68 [60; 75]; 44% women; median baseline NIHSS score: 11 [8;16] points; median onset to treatment time: 2.4 [1.8; 3.1] h. 73% of patients (12947/17 636) received thrombolytic therapy in the first three hours from symptoms onset. The rate of symptomatic ICH according to the ECASS III criteria was 2% [1.8; 2.2] (356/17636), to the SITS-MOST criteria — 2% [1.8; 2.1] (330/17 636). All-cause mortality on day 90 was 9% [8.6; 9.4] (1588/17 636). The number of patients with mRS 0—2 score on day 90 was 61% [60.5; 61.9] (10799/17636). All safety and efficacy outcomes were comparable with FRIDA randomised clinical trial results. Conclusion. The presented data confirm that intravenous thrombolysis with Fortelyzin is safe and effective in routine clinical practice when used within 4.5 h of AIS symptoms onset. These findings should encourage the wider usage of thrombolytic therapy for suitable patients.

This study aimed to assess the prognostic value of the THRIVE scale in patients aged ≥ 60 years with acute ischemic stroke (AIS) after intravenous thrombolysis with the non-immunogenic staphylokinase compared with alteplase. The post-hoc analysis of FRIDA trial results was performed and enrolled patients aged ≥ 60 years were divided into two groups in accordance with the modified Rankin scale (mRS) score on day 90: good-outcome (mRS 0–2) and poor-outcome (mRS 3–6) groups. The receiver operating characteristic (ROC) curves were compared using Delong test. For all-cause mortality on day 90 the predicted AUC value by the THRIVE scale was 0.8 (0.71–0.9) in the non-immunogenic staphylokinase group and 0.76 (0.66–0.87) in the alteplase group (p = 0.57). For poor outcome, AUC value was 0.73 (0.64–0.82) in the non-immunogenic staphylokinase group and 0.79 (0.71–0.87) in alteplase group (p = 0.36). Thus, our study confirmed the prognostic value of the THRIVE scale to predict the outcomes of the patients aged ≥ 60 years treated with the non-immunogenic staphylokinase. Graphical abstract

Vitaphospholip®, a water-soluble form of phosphatidylcholine, has been evaluated in a clinical trial aimed at reducing non-HDL-cholesterol (non-HDL-C) and triglyceride (TG) levels in patients with combined hyperlipidemia. The randomized, double-blind, placebo-controlled study included 100 patients. Vitaphospholip® or placebo was administered orally 500 mg twice a day for 12 weeks.Treatment with Vitaphospholip® resulted in a 13.2% decrease in non-HDL-C compared to 4.3% in the placebo group (p = 0.001). The absolute decrease of non-HDL-C was 0.6 mmol/l compared to -0.2 mmol/l in the placebo group (p = 0.001). The target non-HDL-C level of less than 3.4 mmol/L was achieved in 15 of 39 patients (38.5%) in the Vitaphospholip® group versus 2 of 41 patients (4.9%) in the placebo group (p = 0.000). The absolute decrease of TG in the group of patients treated with Vitaphospholip® was -0.7 mmol/l versus -0.1 mmol/L in the placebo group (p = 0.001). During therapy with Vitaphospholip®, a significant decrease in the levels of apolipoprotein B, total cholesterol, and very low-density lipoprotein cholesterol was observed. No changes in liver or kidney function, vital signs, or ECG were registered. No serious adverse events were identified. Thus, Vitaphospholip® significantly reduced the levels of non-HDL-C, TG, and atherogenic lipoprotein in patients with combined hyperlipidemia and moderate cardiovascular risk.