Mausaminben Hathidara, MD
Al-Shahi Salman R, Minks DP, Rodrigues MA, Bhatnagar P, du Plessis JC, Joshi Y, et al. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial. Lancet Neurol. 2019;18:643-652.
Due to high prevalence of vascular diseases, almost one-third of adults in high-income countries are taking antithrombotic (antiplatelet or anticoagulation). Whether it is beneficial to restart antiplatelet after spontaneous intracerebral hemorrhage (ICH) to prevent another vascular occlusive disease such as stroke, myocardial infarction, or peripheral arterial disease is a dilemma to clinicians due to fear of recurrence of ICH. To date, our knowledge to weigh risk and benefits in this situation is derived from observational and retrospective studies. Recently published, RESTART1 was the first prospective, randomized, open-label and blinded end point trial showing evidence that the risk of recurrent intracerebral hemorrhage was very small against the benefit of antiplatelets for secondary prevention. However, some of the sub-groups such as lobar hemorrhage and presence of cerebral microbleed have higher risk of recurrence intracerebral hemorrhage per observational studies,2,3,4 and whether the benefit still exceeds the risk amongst them is unclear.
The sub-group analysis performed by Dr. Al-Shahi Salman et al. recruited patients >18 years with spontaneous intracerebral hemorrhage who were already on antiplatelet or anticoagulation at the time of hemorrhage and after which therapy was discontinued. 537 participants were enrolled, of whom 525 (98%) had intracerebral hemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy), and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). Participants were followed for a median of 2 years to look for primary outcome as recurrence of intracerebral hemorrhage and secondary outcome of vascular occlusive events.
For this sub-group analysis, the authors studied CT characteristics of ICH such as lobar Vs deep Vs infratentorial. Using Edinburgh criteria for cerebral amyloid angiopathy (finger like projections and subarachnoid extension) predicted 6% (29 of total 499 patients) had high probability and 33% (165 patients) had lower probability. Participants’ brain CT commonly showed previous vascular lesions (316 [62%] of 507), severe periventricular lucencies (195 [38%]), and moderate to severe atrophy (80 [16%]). There were small baseline imbalances in intraventricular extension, subarachnoid extension, and periventricular lucencies. In this prespecified exploratory subgroup analysis of CT features, they did not find strong evidence of statistically significant heterogenicity in the effect of antiplatelet therapy on recurrent intracerebral hemorrhage or ischemic stroke. They also evaluated MRI sub-group clinical and radiographic characteristics (for both groups, 122 on antiplatelets and 132 avoiding antiplatelets) such as: age, sex, white matter changes, superficial siderosis, cerebral microbleed location and volume (divided in three groups 0-1, 2-4, 5 and more), atrophy score for both groups. The authors did not find any clinical or statistically significant hazardous effects of antiplatelet therapy on recurrent intracerebral hemorrhage.
These outcome findings are different compared to previous observational trials. This study has limitations such as the median ICH volume was <5ml in all groups and patients were recruited at median 76 days from intracerebral hemorrhage, suggesting cohort population with less severe ICH and predicted good functional outcome at 6 months to begin with. Therefore, these findings would be only applicable to a particular group of ICH patients and cannot be generalized with bigger volume of ICH, patients with poor functional outcome after primary ICH. There were small differences in baseline characteristics in the MRI sub-group for location of ICH, location of most of cerebral microbleed (lobar Vs subcortical), superficial siderosis. It is also possible that hazardous effect was not seen since the sample size was underpowered, which diminished the precision of the findings. Despite the above limitations, this is the only prospective randomized trial to date showing no significant hazardous effect of antiplatelets even with a traditionally considered high-risk patient population for ICH recurrence with CT and MRI characteristics as discussed above in detail. These findings need to be replicated with a larger cohort.
- Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. RESTART Collaboration*
- Charidimou A, Boulouis G, Roongpiboonsopit D, et al. Cortical superficial siderosis and recurrent intracerebral hemorrhage risk in cerebral amyloid angiopathy: large prospective cohort and preliminary metaanalysis. Int J Stroke 2019; published online Feb 20. DOI:10.1177/1747493019830065.
- Charidimou A, Imaizumi T, Moulin S, et al. Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: a metaanalysis. Neurology 2017; 89: 820–29.
- Poon MT, Fonville AF, AlShahi Salman R. Longterm prognosis after intracerebral haemorrhage: systematic review and metaanalysis. J Neurol Neurosurg Psychiatry 2014; 85: 660–67.