Safety Of Intra-arterial Thrombolysis Research Articles

Efficacy and safety of intra-arterial thrombolysis in patients with central retinal artery occlusion: a systematic review and meta-analysis.

To investigate the efficacy and safety of intra-arterial thrombolysis (IAT) in patients with central retinal artery occlusion (CRAO). PubMed and EMBASE were searched for potentially eligible studies that reported IAT in CRAO patients from inception to Nov 8, 2021. Standard mean difference (SMD) was pooled to compare visual acuity (VA) at baseline with final in IAT patients. The rates and odds ratios (OR) were meta-analyzed to compare VA improvement in IAT with non-IAT patients, stratified to different times from onset to procedure, different definitions of VA improvement, and three CRAO stages. Adverse effects were recorded. Fifteen studies were included, enrolling 507 CRAO patients who received IAT and 296 CRAO patients who did not. VA was significantly improved from baseline to final VA in IAT patients (SMD [LogMAR] 0.70, 95% CI [0.51, 0.90]). VA improvement rate was higher in IAT patients than that in non-IAT (56% vs 32%, OR 3.55, 95%CI [1.74, 7.24]), with greater OR in IAT within 6h from onset to procedure (OR 4.60, 95%CI [1.24, 16.99]) than that beyond 6h (OR 3.36, 95%CI [1.43, 7.85]). The benefit remained consistent when VA improvement was defined as ≥ 3 lines on the Snellen chart (OR 4.68, 95%CI [2.10, 10.41]) and was even greater when CRAO was incomplete. Five patients had a symptomatic intracranial hemorrhage and 21 patients had ischemic stroke or transient ischemic attack after IAT. IAT treatment has certain potential in ameliorating VA in CRAO patients, which should be balanced against cerebral complications.

Intra-Arterial Thrombolysis Vs. Mechanical Thrombectomy in Acute Minor Ischemic Stroke Due to Large Vessel Occlusion.

BackgroundThe efficacy and safety of mechanical thrombectomy (MT) in acute large vessel occlusion (LVO) patients with minor stroke (NIHSS ≤ 5) remains undetermined. We aimed to compare the efficacy and safety of intra-arterial thrombolysis (IAT) alone vs. MT for LVO patients with minor stroke.MethodsPatients were selected from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry, a prospective multicenter registry study, and divided into MT and IAT alone groups. We compared the outcome measures between the two groups, including 90-day functional outcome evaluated by the modified Rankin Scale (mRS), the final recanalization level, intracranial hemorrhage, and mortality within 90-days by logistic regression models with adjustment. Besides the conventional multivariable analysis, we performed a sensitivity analysis by adjusting the propensity score to confirm our results. The propensity score was derived using a logistic regression model.ResultsOf the 120 patients, 63 received IAT alone and 57 received MT as the first-line treatment strategy. As compared to MT group, patients in the IAT alone group were associated with a higher chance of 90-day mRS 0-2 [93.7% vs. 71.9%, odds ratio (OR) = 4.75, 95% confidence interval (CI): 1.20–18.80, P = 0.027], a high chance of 90-day mRS 0-3 (96.8% vs. 86.7%, OR = 11.35, 95% CI: 1.93–66.86, P = 0.007), a shorter median time from puncture to recanalization (PTR) (60 min vs. 100 min, β = −63.70, 95% CI: −81.79– −45.61, P < 0.001), a lower chance of any intracranial hemorrhage (ICH) within 48 h (3.2% vs. 19.3%, OR = 0.15, 95% CI: 0.03–0.79, P = 0.025), and a lower chance of mortablity within 90 days (1.6% vs. 9.2%, OR = 0.05, 95% CI: 0.01–0.57, P = 0.016). Similarly, the sensitivity analysis showed the robustness of the primary analysis.ConclusionsCompared with MT, IAT may improve 90-day clinical outcomes with decreased ICH rate and mortality in LVO patients with minor stroke.

Efficacy and Safety of Intra-Arterial Thrombolysis in Central Retinal Artery Occlusion

To investigate the efficacy and safety of intra-arterial thrombolysis (IAT) for acute central retinal artery occlusion (CRAO). Records from 101 CRAO patients treated with either IAT (n = 57) or standard treatment (ST; n = 44) were retrospectively reviewed. ST consisted of ocular massage and intraocular pressure-lowering agents. We used fundoscopic and angiographic findings to categorize CRAO as incomplete (diminished visual acuity [VA] with slight retinal edema, slight cherry-red spot), subtotal (severe VA reduction, cherry-red spot, distinct retinal edema), or total (massive edema, occluded perimacular arterioles, additional choroidal blood flow interruption). One-month and final best-corrected VA (BCVA) of the IAT group were compared with those of the ST group. Early (≤3-day) and final (1-month) reperfusion (improvement of retinal perfusion) rates were compared between groups. Subgroup analyses were performed according to CRAO stage. Overall, VA did not significantly differ between groups, but early reperfusion was greater in the IAT group (74.1% vs. 42.9%, P = 0.005). In incomplete CRAO, the IAT group exhibited greater visual improvement after 1 month (1.08 ± 0.21 vs. 0.23 ± 0.26 logarithmic values of the minimum angle of resolution [logMAR], P < 0.001) and at the final visit (1.08 ± 0.53 vs. 0.08 ± 0.57 logMAR, P < 0.001). However, in subtotal and total CRAO, no significant differences in visual outcomes were observed between groups. IAT resulted in clinically insignificant cerebral infarcts, detectable on brain imaging, in 8% of patients. Hemorrhagic transformation was not noted. The IAT treatment may provide early restoration of retinal perfusion and offer functional benefits in the management of incomplete CRAO.

Intra-Arterial Thrombolysis vs. Standard Treatment or Intravenous Thrombolysis in Adults with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Recent evidence has suggested that intra-arterial thrombolysis may provide benefit beyond intravenous thrombolysis in ischemic stroke patients. Previous meta-analyses have only compared intra-arterial thrombolysis with standard treatment without thrombolysis. The objective was to review the benefits and harms of intra-arterial thrombolysis in ischemic stroke patients. We undertook a meta-analysis of randomized controlled trials comparing the efficacy and safety of intra-arterial thrombolysis with either standard treatment or intravenous thrombolysis following acute ischemic stroke. Primary outcomes included poor functional outcomes (modified Rankin Scale 3-6), mortality, and symptomatic intracranial hemorrhage. Study quality was assessed, and outcomes were stratified by comparison treatment received. Four trials (n = 351) comparing intra-arterial thrombolysis with standard treatment were identified. Intra-arterial thrombolysis reduced the risk of poor functional outcomes (modified Rankin Scale 3-6) [relative risk (RR) = 0·80; 95% confidence interval = 0·67-0·95; P = 0·01]. Mortality was not increased (RR = 0·82; 95% confidence interval = 0·56-1·21; P = 0·32); however, risk of symptomatic intracranial hemorrhage was nearly four times more likely (RR = 3·90; 95% confidence interval = 1·41-10·76; P = 0·006). Two trials (n = 81) comparing intra-arterial thrombolysis with intravenous thrombolysis were identified. Intra-arterial thrombolysis was not found to reduce poor functional outcomes (modified Rankin Scale 3-6) (RR = 0·68; 95% confidence interval = 0·46-1·00; P = 0·05). Mortality was not increased (RR = 1·12; 95% confidence interval = 0·47-2·68; P = 0·79); neither was symptomatic intracranial hemorrhage (RR = 1·13; 95% confidence interval = 0·32-3·99; P = 0·85). Differences in time from symptom onset-to-treatment and type of thrombolytic administered were found across the trials. This analysis finds a modest benefit of intra-arterial thrombolysis over standard treatment, although it does not find a clear benefit of intra-arterial thrombolysis over intravenous thrombolysis in acute ischemic stroke patients. However, few trials, small sample sizes, and indirectness limit the strength of evidence.

Intra-Arterial vs Intra-Venous Thrombolysis for Anterior Cerebral Occlusion

The safety and effectiveness of intra-arterial thrombolysis (IAT) in comparison to intravenous thrombolysis (IVT) for the treatment of ischemic stroke is uncertain. Our study aims to assess and compare IAT to IVT for clinically relevant outcomes in patients with occlusion of the anterior cerebral circulation. Patients with acute ischemic stroke were enrolled for either treatment; those whose symptoms occurred within 4.5 hrs after stroke were treated with IVT, whereas those who presented < 4.5 hrs but had contraindications to IVT or presented between 4.5 and 6 hrs were treated with IAT. Evaluated endpoints included: disability at 90 days as measured by the modified Rankin Scale (mRS), incidence of mortality, and incidence of symptomatic intracranial haemorrhage. 78 patients with anterior cerebral circulation occlusion were included in the study (55 in IVT, 23 in IAT). After 90 days, 82.6% patients treated with IAT reached independence in comparison to 56.4% in the IVT group (P = 0.028, RR = 2.66, 95% CI: 1.10-7.04). The incidence of all intracranial haemorrhages in the IAT and IVT groups respectively were 30.4% and 12.7% (P = 0.103, RR = 2.391, 95% CI: 0.946-6.047); symptomatic intracranial haemorrhage occurred in 8.7% and 9.1% of patients (P = 1.00, RR = 0.957, 95% CI: 0.200-4.579), and mortality in 8.7% and 16.4% (P = 0.492, RR = 1.882, 95% CI: 0.440-8.045). Results suggest that IAT is more effective than IVT in allowing patients to achieve independence. While inconclusive, the safety of IAT within 6 hrs is comparable to IVT within 4.5 hrs.

The Role of Recombinant Pro-urokinase (r-pro-UK) and Intra-arterial Thrombolysis in Acute Ischaemic Stroke: the PROACT Trials

SUMMARYBy delivering a higher concentration of drug directly into a clot, intra-arterial (IA) thrombolysis may be more effective than intravenous therapy at opening a blocked artery. The clinical efficacy and safety of IA thrombolysis with the selective thrombolytic r-pro-urokinase (r-pro-UK) has been demonstrated in two randomized acute stroke treatment trials, PROACT I and PROACT II.However, IA pro-UK is not yet FDA approved, and it is not known if IA thrombolysis with other agents would have the same results. However the American Heart Association has deemed IA thrombolysis an 'acceptable alternative therapy' and many stroke centres are offering it to patients with a major acute stroke presenting within 6 h.

Safety and efficacy of intraarterial thrombolysis for perioperative stroke after cardiac operation

Background. Acute ischemic stroke after cardiac operations is a devastating complication with limited therapeutic options. As clinical trials of thrombolysis for acute ischemic stroke exclude patients with recent major surgery, the safety of intraarterial thrombolysis in this setting is unknown. Methods. Thirteen patients with acute ischemic stroke within 12 days of cardiac operation underwent intraarterial thrombolysis within 6 hours of stroke symptom onset. The National Institutes of Health Stroke Scale was used to assess neurologic recovery. Results. The mean age was 69 years (standard deviation ±5 years) and 62% were men. Cardiac procedures included valve operations in 6 patients, coronary artery bypass grafting in 4, valve and coronary artery bypass grafting in 2, and left ventricular assist device in 1 patient. Atrial fibrillation occurred in 5 patients (38%). The mean time from operation to stroke was 4.3 days (standard deviation ± 3 days). Thrombolysis was initiated within 3.6 hours (standard deviation ±1.6 hours) of stroke symptom onset. Recanalization was complete in 1 patient, partial in 5, and 7 patients had low flow. Neurologic improvement occurred in 5 patients (38%). One patient needed a chest tube for hemothorax, 2 others were transfused for low hemoglobin. No operative intervention for bleeding was necessary. Conclusions. In select patients with acute ischemic stroke after recent cardiac operation, intraarterial thrombolysis appears to be reasonably safe and may lead to neurologic recovery.

Safety of intra-arterial thrombolysis in the postoperative period.

Limited systemic fibrinolysis and reduced dosage are features of intra-arterial thrombolyis (IAT) that may be advantageous in the treatment of postoperative strokes. However, IAT may increase the risk of surgical bleeding. We sought to determine the safety of postoperative IAT. This was a retrospective case series from 6 university hospitals. All cases of IAT within 2 weeks of surgery were identified. Demographics, stroke mechanism, stroke severity, imaging and angiographic findings, time between surgery and lysis, thrombolytic agent used, surgical site bleeding, intracranial bleeding, and mortality rates were determined. Death or complications directly related to IAT were determined. Thirty-six patients (median age, 71.5 years; range, 45 to 85) were identified. Median time from surgery to stroke was 21.5 hours (range, 1 to 120). Open heart surgery was done in 18 (50%), carotid endarterectomy in 6 (17%), craniotomy in 3 (8%), ophthalmologic-ear, nose and throat surgery in 2 (6%), urologic-gynecologic surgery in 4 (11%), orthopedic surgery in 2 (6%), and plastic surgery in 1 (3%). The stroke causes were cardioembolism in 24 (67%), large-vessel atherosclerosis in 4 (11%), dissection in 3 (8%), postendarterectomy occlusion in 4 (11%), and radiation arteriopathy in 1 (3%). Median time to angiogram was 2.5 hours (0.1 to 5.5). Occlusion sites were M1 in 19 (53%), M2 in 9 (25%), internal carotid artery in 5 (14%), basilar artery in 2 (6%), and posterior communicating artery in 1 (3%). Thrombolysis was completed at a median of 4.5 hours (range, 1 to 8.0). Tissue plasminogen activator was used in 19 (53%) and urokinase in 17 (47%). Nine (26%) patients died. Surgical site bleeding occurred in 9 (25%) cases (minor in 6, major in 3). The major surgical bleeds were 2 post-craniotomy intracranial hemorrhages and 1 hemopericardium after coronary artery bypass grafting; all were fatal. Six deaths were non-IAT related: 3 caused by cerebral edema and 3 by systemic causes. Major bleeding complications were significantly more common among patients with craniotomy (P<0.02). Postoperative IAT carries a risk of bleeding in up to 25% of patients but is usually minor surgical site bleeding. Avoiding IAT in intracranial surgery patients may reduce complications. Mortality rate in this series was similar to that reported in prior IAT trials. IAT remains a viable therapeutic option for postoperative strokes.

Intraoperative lytic therapy: agents and methods of administration.

Intraoperative intraarterial thrombolysis is a valuable adjunct for the removal of residual arterial thrombi after mechanical thromboembolectomy. Early reports by some investigators indicated high rates of bleeding complications, most likely caused by inappropriately high doses of plasminogen activators infused over long periods of time, which led to systemic lytic effects. Animal models and controlled human experiments subsequently have shown the potential efficacy and safety of intraarterial thrombolysis. Since urokinase (UK) has been withdrawn from the market, recombinant tissue-type plasminogen activator (rt-PA) has become the plasminogen activator of choice. Reteplase and other plasminogen activators may be beneficial (and safe); however, data on intraoperative use currently are not available. The most common methods of delivery into the distal arterial tree are bolus infusion with inflow occlusion, drip infusion after restoration of arterial inflow, and the isolated limb perfusion technique. The number of distal vessels involved, the amount of residual thrombus, and severity of ischemia guide the dose of plasminogen activator, volume of perfusate, and the technique and duration of infusion.