Are antiplatelets and anticoagulants safe and beneficial in people with cavernomas?

Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis.

Zuurbier SM, Hickman CR, Tolias CS, et al; Scottish Audit of Intracranial Vascular Malformations Steering Committee.

Lancet Neurol 2019; 18:935-941.



Antithrombotic (anticoagulant or antiplatelet) therapy is withheld from some patients with cerebral cavernous malformations, because of uncertainty around the safety of these drugs in such patients. We aimed to establish whether antithrombotic therapy is associated with an increased risk of intracranial haemorrhage in adults with cerebral cavernous malformations.


In this population-based, cohort study, we used data from the Scottish Audit of Intracranial Vascular Malformations, which prospectively identified individuals aged 16 years and older living in Scotland who were first diagnosed with a cerebral cavernous malformation during 1999-2003 or 2006-10. We compared the association between use of antithrombotic therapy after first presentation and the occurrence of intracranial haemorrhage or persistent or progressive focal neurological deficit due to the cerebral cavernous malformations during up to 15 years of prospective follow-up with multivariable Cox proportional hazards regression assessed in all individuals identified in the database. We also did a systematic review and meta-analysis, in which we searched Ovid MEDLINE and Embase from database inception to Feb 1, 2019, to identify comparative studies to calculate the intracranial haemorrhage incidence rate ratio according to antithrombotic therapy use. We then generated a pooled estimate using the inverse variance method and a random effects model.


We assessed 300 of 306 individuals with a cerebral cavernous malformation who were eligible for study. 61 used antithrombotic therapy (ten [16%] of 61 used anticoagulation) for a mean duration of 7·4 years (SD 5·4) during follow-up. Antithrombotic therapy use was associated with a lower risk of subsequent intracranial haemorrhage or focal neurological deficit (one [2%] of 61 vs 29 [12%] of 239, adjusted hazard ratio [HR] 0·12, 95% CI 0·02-0·88; p=0·037). In a meta-analysis of six cohort studies including 1342 patients, antithrombotic therapy use was associated with a lower risk of intracranial haemorrhage (eight [3%] of 253 vs 152 [14%] of 1089; incidence rate ratio 0·25, 95% CI 0·13-0·51; p<0·0001; I2=0%).


Antithrombotic therapy use is associated with a lower risk of intracranial haemorrhage or focal neurological deficit from cerebral cavernous malformations than avoidance of antithrombotic therapy. These findings provide reassurance about safety for clinical practice and require further investigation in a randomised controlled trial.


See also

Bervini D, Jaeggi C, Mordasini P, Schucht P, Raabe A. Antithrombotic medication and bleeding risk in patients with cerebral cavernous malformations: a cohort study. J Neurosurg 2018; doi: 10.3171/2018.1.JNS172547 (Epub ahead of print).

Both papers are cited in the neurochecklist:

Cerebral cavernous malformations (cavernomas): clinical features

Abstract link 1

Abstract link 2

By Karlo J Lizarraga and Antonio AF De Salles –, CC BY 2.5, Link

Is intracerebral haemorrhage worse with prior antiplatelet use?

Association between previous use of antiplatelet therapy and intracerebral hemorrhage outcomes

Khan NI, Siddiqui FM, Goldstein JN, et al.

Stroke 2017; 48:1810-1817.



Although the use of antiplatelet therapy (APT) is associated with the risk of intracerebral hemorrhage (ICH), there are limited data on prestroke APT and outcomes, particularly among patients on combination APT (CAPT). We hypothesized that the previous use of antiplatelet agents is associated with increased mortality in ICH.


We analyzed data of 82 576 patients with ICH who were not on oral anticoagulant therapy from 1574 Get with the Guidelines-Stroke hospitals between October 2012 and March 2016. Patients were categorized as not on APT, on single-APT (SAPT), and CAPT before hospital presentation with ICH. We described baseline characteristics, comorbidities, hospital characteristics and outcomes, overall and stratified by APT use.


Before the diagnosis of ICH, 65.8% patients were not on APT, 29.5% patients were on SAPT, and 4.8% patients were on CAPT. There was an overall modest increased in-hospital mortality in the APT group versus no APT group (24% versus 23%; adjusted odds ratio, 1.05; 95% confidence interval, 1.01-1.10). Although patients on SAPT and CAPT were older and had higher risk profiles in terms of comorbidities, there was no significant difference in the in-hospital mortality among patients on SAPT versus those not on any APT (23% versus 23%; adjusted odds ratio, 1.01; 95% confidence interval, 0.97-1.05). However, in-hospital mortality was higher among those on CAPT versus those not on APT (30% versus 23%; adjusted odds ratio, 1.50; 95% confidence interval, 1.39-1.63).


Our study suggests that among patients with ICH, previous use of combination, but not single, antiplatelets was associated with higher risk for in-hospital mortality.

This reference is now cited in the neurochecklist:

Intracerebral haemorrhage (ICH): prognosis and outcome

Abstract link

By Steve Mike NeefOwn work, CC BY-SA 3.0, Link