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Cerebral microbleeds should not preclude anticoagulation

JAMA Neurology
Reuters Health - 29/10/2020 - The presence of cerebral microbleeds should not be a contraindication to anticoagulation in patients with embolic stroke of undetermined source (ESUS), according to a subgroup analysis of the NAVIGATE ESUS trial.

"Patients with embolic stroke of undetermined source who had small occult brain bleeds or 'microbleeds' seen on brain MRI responded similarly to rivaroxaban (compared with aspirin) as patients without microbleeds," Dr. Ashkan Shoamanesh of McMaster University, in Hamilton, Canada, told Reuters Health by email.

Cerebral microbleeds (CMBs), present in a third of patients with ischemic stroke, have been associated with recurrent stroke and intracerebral hemorrhage. This association calls into question the safety of anticoagulant therapy in patients with stroke and cerebral microbleeds.

Dr. Shoamanesh and colleagues investigated whether microbleeds affected the rates of recurrent stroke or the responses to anticoagulation in their analysis of 3,699 participants in the NAVIGATE ESUS randomized controlled trial.

Eleven percent had at least one CMB on the MRI. Independent predictors of CMBs included advancing age, East Asian race/ethnicity, hypertension, multiterritorial ESUS, chronic infarcts, and occult intracerebral hemorrhage (ICH).

The burden of disease (according to CMB count) was mild in 68% of participants, moderate in 27% and severe in 5%.

During a median follow-up of 11 months, the rate of recurrent stroke of any type was significantly higher among participants with CMBs (7.7 per 100 person-years) than among those without CMBs (5.0 per 100 person-years), the researchers report in JAMA Neurology.

The rate of recurrent stroke increased with greater CMB burden, from 5.6 per 100 person-years with mild disease to 8.5 per 100 person-years with moderate-severe disease to 12.1 per 100 person-years in individuals with strictly lobar CMBs.

Study participants with CMBs had a 4.18-fold increased risk of ICH (1.0 per 100 person-years vs. 0.2 per 100 person-years for participants without CMBs), and this risk also increased with greater CMB burden (0.5 per 100 person-years with mild disease and 3.0 per 100 person-years with moderate-severe disease).

The rate of all-cause death was significantly higher in patients with CMBs (2.5 per 100 person-years) than in patients without CMBs (1.2 per 100 person-years), regardless of CMB burden.

The risk of recurrent stroke for patients randomized to rivaroxaban versus aspirin did not differ significantly among patients with CMBs or among those without CMBs, and the presence of CMBs did not alter the effect of rivaroxaban versus aspirin on the secondary outcomes of ischemic stroke, ICH, or all-cause mortality.

"Current evidence does not support the use of cerebral microbleeds on MRI to stratify anticoagulant decision making (particularly with non-vitamin K antagonist oral anticoagulants) where otherwise indicated in ischemic stroke patients," Dr. Shoamanesh said.

"As the underlying small-vessel diseases that form microbleeds in older age are believed to be similar across ischemic stroke subtypes, our findings likely generalize to all ischemic stroke patients," he said. "Accordingly, our findings support the continued use of blood thinners in patients with ischemic stroke who are incidentally found to have these lesions on imaging."

"Whether microbleeds can modify the effect of anticoagulation in ICH survivors towards net harm has yet to be assessed in randomized controlled trials and remains uncertain," Dr. Shoamanesh said. "MRI substudies of several ongoing trials assessing optimal stroke prevention in ICH survivors with atrial fibrillation, such as the ongoing global ENRICH-AF trial, will ultimately provide more insights in this regard."

"CMBs should not be considered independent lesions associated with risks on their own," write Dr. Laurent Puy and Dr. Charlotte Cordonnier of Universite Lille, in France, in a linked editorial. "Yes, CMBs are markers of the severity of the underlying vessel disease, but they are just one among others."

"In the era of precision medicine, we should take into account the nature of the ongoing underlying vessel disease by looking at all types of lesions (white matter hyperintensities, enlarged perivascular spaces, superficial siderosis, atrophy, and lacunes)," they conclude. "Gathering different lines of imaging biomarkers in each individual should be encouraged to precisely understand the individual benefit-risk balance of antithrombotic treatment."

Dr. Yuji Ueno of Juntendo University School of Medicine, in Tokyo, Japan, who recently reviewed the underlying pathology of CMB in cryptogenic stroke but was not involved in the new study, told Reuters Health by email, "Physicians should be aware of the presence of microbleeds, (but) the optimal antithrombotic treatments for ESUS are still unknown."

By Will Boggs MD

SOURCE: https://bit.ly/35sEYSD and https://bit.ly/3jgFfg6 JAMA Neurology, online October 19, 2020

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