Antithrombotics after a stroke: In whom, when and how?

Large well-designed studies published in recent years point to an association of cerebral microbleeds (CMBs) with increased risks of intracerebral haemorrhage (ICH) and ischaemic stroke (IS). Although the association of CMBs with ICH is greater than with IS, the absolute incidence of IS is still higher than of ICH, implying that antithrombotics should not be routinely withheld for all patients with CMBs.

“CMBs are an MRI marker of small vessel disease and are commonly present in patients of advanced age and those with cognitive impairment, hypertension or history of stroke, particularly haemorrhagic stroke,” said Dr Yannie Soo of Union Hospital, Hong Kong, and the Division of Neurology, Chinese University of Hong Kong, at AIM 2022. “CMBs’ association with both ICH and IS creates a clinical dilemma for using antiplatelets and anticoagulants for IS prevention in patients with CMBs.” [Lancet Neurol 2019;18:653-665]

The prospective, randomized, open-label, blinded-endpoint, parallel-group RESTART trial, conducted across 122 hospitals in the UK, assessed whether starting antiplatelet therapy (n=252) might reduce the risk of recurrent symptomatic ICH compared with avoiding antiplatelet therapy (n=255). The study found no clinically or statistically significant hazards of antiplatelet therapy on recurrent ICH in primary subgroup analyses of CMB presence. [Lancet Neurol 2019;18:643-652]

“At the same time, the risks of ICH and IS are different in patients with microbleeds, atrial fibrillation [AF], history of stroke, or transient ischaemic attack,” noted Soo.

A Microbleeds International Collaborative Network (MICON) pooled individual patient analysis evaluated the risk of subsequent ICH vs IS in patients with AF and CMBs (n=7,839) taking one of the four common antithrombotic regimens: a vitamin K antagonist, a direct-acting oral anticoagulant (DOAC), an antiplatelet agent, or a combination regimen of an anticoagulant and an antiplatelet agent.

“DOACs were found to be the safest among all antithrombotic regimens,” said Soo, citing unpublished data. “Patients with AF and recent IS were found to be at increased risk of vascular events, necessitating concurrent use of an antiplatelet agent. Furthermore, patients with AF receiving a combination of an anticoagulant and an antiplatelet and with high CMB burden have a higher absolute rate of ICH vs IS. Further studies are needed for optimizing stroke prevention in this high-risk group.”

A Swedish study of 2,619 ICH survivors found that antiplatelet use was associated with increased risks of thrombotic stroke and vascular death across all time points, and was not associated with lower risk of subsequent ICH. At the same time, it was found that early initiation of anticoagulation may increase the risk of bleeding. In patients with AF, the benefit from anticoagulation therapy was found to be the greatest when initiated 7–8 weeks after the first ICH. [Stroke 2017;48:314-320]

“The measures that need to be implemented to mitigate the risk of ICH in all patients with CMBs are: choosing an agent with the lowest risk of ICH [eg, DOAC], minimizing the duration of combination therapy in patients with AF, avoiding NSAIDs, frequent monitoring of international normalized ratio with warfarin use and renal function with DOAC use, and stringent blood pressure control,” advised Soo.