Use of antithrombotics alongside endovascular stroke therapy is ill-advised, lest patients have a treatment-induced intracranial haemorrhage, a major study has shown.

While some observational studies have suggested benefit with antiplatelets or unfractionated heparin, the first randomised clinical trial of intravenous aspirin and low molecular weight heparin with thrombectomy found the combination increased risk of intracranial bleeding without providing any functional benefit to patients.

Previous studies have reported mixed results with antiplatelet-endovascular therapies, ranging from improved microvascular reperfusion and functional outcomes plus slight to moderately-elevated risk of intracranial haemorrhage, to no net effect on ischaemic stroke patients in general.

Published in The Lancet, the Dutch MR CLEAN trial assessed disability and safety outcomes in 628 ischaemic stroke patients who had an intracranial large-vessel occlusion in the anterior chamber and could start endovascular treatment within six hours of symptom onset.

They received either a 300 mg bolus of IV aspirin, no aspirin and/or a moderate dose of unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose heparin (5000 IU bolus followed by 500 IU/h for 6 h) or no heparin, during treatment.

The study showed aspirin and heparin recipients had a higher risk of intracranial haemorrhage versus non-users at 14% versus 7% (adjusted odds ratio [OR]: 1.95, 95% CI: 1.13–3.35) and 13% versus 7% (adjusted OR: 1.98, 95% CI: 1.14–3.46), respectively.

Together, the drugs were also associated with worse, though not significantly different, Rankin Scale scores at 90 days follow-up, signalling increased functional disability compared with pre-stroke capabilities (adjusted common OR: 0.91, 95% CI: 0.69–1.21).

The poor outcomes outweighed any recanalisation benefit seen in heparin users and put an early stop to the trial, which planned to enrol 1,500 patients.

The results suggest routine periprocedural treatment with aspirin or unfractionated heparin — particularly in the studied doses — should be avoided and that this “might increase chances of recovery after endovascular stroke treatment”, the authors wrote.

They also advised against using lower dosages in endovascular therapy or other indications, such as acute carotid stenting), until their safety and efficacy have been further evaluated.

Fortunately, “routine periprocedural use of antiplatelet or anticoagulation is already not done in most centres,” an accompanying editorial stated.

“Current guidelines discourage heparin use in combination with intravenous thrombolytics and recommend postponing antiplatelets start after thrombolytic therapy.”

The quest to bridge the gap between stroke patients with successful endovascular reperfusion and those who attain favourable outcomes continues.

Yet, reviewing the effect of antithrombotics in stroke patients undergoing thrombectomy was a worthy cause, the editorial suggested, since incomplete microvascular reperfusion is a potential mechanism behind the gap.

“These microthrombi either form in situ by the slow flow state while the occlusion is ongoing or result from distal migration of emboli from the proximal occlusion,” the editorial read.

“These observations justified testing the adjunctive use of antiplatelet or anticoagulant therapies to treat microcirculatory occlusion that persists even after recanalisation of the primary occlusion.”

The study did have some limitations, including failure to exclude patients who were previously on antiplatelets or anticoagulants — and therefore — already at higher haemorrhagic risk of intravenous thrombolysis, and treatment delays — where nearly 500 patients were transferred from the primary hospital before treatment.

“No details about the transport time or door-in-door-out time for the transferred patients exist. Delays of transfer affect the outcome even when the onset to puncture time is relatively short,” the editorial read.

Despite this, the editorialists agreed that there probably isn’t a place for anticoagulation or antiplatelet therapy in stroke patients on thrombolytic therapy before thrombectomy. Questions remain on whether the drugs may be helpful in microvascular reperfusion, relative to risks, in those who aren’t candidates for intravenous thrombolysis, it read.