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Triple Therapy: A Safe Inexpensive Regimen of Heparin, Aspirin, and Clopidogrel for Intracranial Vessel Occlusions in Acute Ischemic Stroke Patients Ineligible for Intravenous Thrombolytics and Endovascular Thrombectomy

Chaudhari, A.; Almajali, M.; Khan, N.; Bhattarai, A.; Ramirez-Abreu, D.; Al-Gheeta, J. K.; Almajali, F.; Yaghi, S.; Nguyen, T. N.; Lin, E.; Zaidat, O. O.

2025-10-17 neurology
10.1101/2025.10.14.25338043 medRxiv
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BackgroundEndovascular thrombectomy (EVT) has revolutionized acute ischemic stroke management but remains inaccessible to many patients due to anatomical, clinical, or logistical barriers. Treatment strategies for patients with intracranial occlusions who are ineligible for intravenous thrombolysis remain undefined. We evaluated the safety of short-term "Triple Therapy" (TT; heparin, aspirin, clopidogrel) in this population. MethodsWe conducted a retrospective analysis of patients aged 18-90 with symptom onset [&le;]24 hours, radiologically confirmed intracranial occlusion, NIHSS [&le;]10, and ineligibility for intravenous thrombolysis. Patients received either TT for 48-72 hours or EVT (serving as controls). Primary outcomes included symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), extracranial hemorrhage, and 30-day mortality. Secondary outcomes included vessel recanalization, NIHSS change, ICU/hospital stay, and modified Rankin Scale (mRS) at 90 days. ResultsForty-seven patients met criteria (median age: 63 years; 43% female); 25 received TT, 22 underwent EVT. TT patients had lower baseline NIHSS (2.44{+/-}2.79 vs. 6.59{+/-}2.77; p<0.001). No sICH occurred with TT vs. 2 cases (9.1%) in EVT (p=0.20). ICH was observed in 8% (TT) vs. 27.3% (EVT) (p=0.11); extracranial hemorrhage rates were similar (4% vs. 4.5%). No 30-day mortality was reported. EVT achieved higher complete recanalization (77.3% vs. 28%; p<0.001), but clinical outcomes were comparable: mean NIHSS change (0.20{+/-}4.22 vs. 0.29{+/-}8.85; p=0.98) and discharge mRS (1.20{+/-}1.22 vs. 2.19{+/-}1.97; p=0.06). ConclusionsShort-term TT showed low hemorrhagic risk, including no sICH, and may offer a safe, accessible treatment alternative for select patients with intracranial occlusions ineligible for thrombolysis or EVT. Comparable clinical outcomes, despite lower recanalization rates, likely reflect the favorable baseline prognosis of TT patients.

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