Almost 90% of strokes are ischemic strokes. LVOs account for one-quarter to almost one-half (24%-46%) of all acute ischemic strokes (AISs). Strokes secondary to LVOs are associated with high rates of morbidity and mortality. The only available treatment options are the use of the IV thrombolytic agent alteplase or the use of endovascular therapy (i.e., mechanical thrombectomy [MT]). Investigators have been exploring the potential of combining both drug therapy and endovascular therapy in an effort to improve prognosis.

The Society of Vascular and Interventional Neurology Guidelines and Practice Standards (GAPS) Committee released a brief practice update statement on the use of IV thrombolysis before MT in patients with LVO AIS. The statement provides a summary of recent trials which have examined the use of combination therapy.

Among the trials highlighted are:

• SKIP: a trial that studied the direct mechanical thrombectomy in acute LVO stroke
• DEVT: a trial that studied direct endovascular thrombectomy versus combined IV thrombolytic and endovascular thrombectomy for patients with acute LVO in the anterior circulation
• DIRECT-MT: a multicenter, randomized clinical trial (RCT) that studied direct intraarterial thrombectomy in order to revascularize AIS Patients with LVO efficiently in Chinese tertiary hospitals
• MR CLEAN NO-IV: a multicenter, RCT of endovascular treatment for AIS in the Netherlands; also known as IV treatment followed by endovascular treatment versus direct endovascular treatment for AIS caused by a proximal intracranial occlusion study protocol
• SWIFT-DIRECT: an RCT that studied Solitair with the intention for thrombectomy plus IV tissue plasminogen activator versus DIRECT Solitair stent-retriever thrombectomy in acute anterior circulation stroke
• DIRECT-SAFE: an RCT of DIRECT endovascular clot retrieval versus standard bridging therapy.

In evaluating the evidence, the GAPS Committee found that noninferiority of MT alone was not achieved in the SKIP, MR CLEAN NO IV, SWIFT-DIRECT, and DIRECT-SAFE trials. There was a nonsignificant association between combination therapy and better functional outcomes in the SKIP trial. DEVT found that noninferiority of MT alone was met during the interim analysis. DIRECT-MT demonstrated that early reperfusion was higher in those who received combination therapy.

Symptomatic intracranial hemorrhage (siCH) did not differ between combination therapy and endovascular monotherapy in the DEVT, DIRECT-MT, or the MR CLEAN NO-IV trials. SWIFT-DIRECT found that reperfusion and functional independence were higher in the combination therapy group than in the MT alone group, but siCH was also higher in the former group. The DIRECT-SAFE trial showed superiority of combination therapy based on modified Rankin scores for Asian patients. Most trials used the standard dose of alteplase at 0.9 mg/kg, except the SKIP trial, which used 0.6 mg/kg.

The BEYOND-SWIFT trial, which was not included in the above statement on combination IV thrombolytic and MT therapy for LVO AIS, showed that while having atrial fibrillation, the use of direct-acting oral anticoagulants or the use of bridging thrombolytic therapy were not significantly associated with siCH; the prior use of vitamin K-antagonists was correlated with increased risk.

Based on the findings from these recent clinical trials, the GAPS Committee recommended combination therapy with IV thrombolytics and MT over MT alone in eligible patients with emergent LVO AIS. Even in facilities that do not have the ability to perform on-site MT, thrombolytic therapy should be initiated, and the patient should be immediately transferred to a center that can perform MT without waiting for completion of alteplase therapy.

This brief practice update provides clarification on the place in therapy of IV thrombolytics as part of combination therapy in LVO AIS for pharmacists who manage patients with stroke. It should help alleviate concerns about the use of combination therapy in this critically ill population.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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