Clotting and Re-bleeding: Focus on ICH survivors

Intracerebral hemorrhage (ICH) is a devastating disease, as while just under a third of strokes are ICH they account for 49% of the global burden of death from stroke. Despite the advances in primary and secondary ischemic stroke prevention, neither the incidence nor the case fatality rates of ICH have substantially decreased since the 1980s, in contrast to the case of ischemic stroke. The management of ICH survivors with co-morbid cardiovascular diseases is particularly challenging, and requires balancing the benefit of ischemic vascular preventative treatments, such as antithrombotic and lipid lowering agents, against their propensity to increase the risk of re-bleeding.

One approach is to identify simply risk factors that can potentially stratify patients into different risk categories. In a recent study with pooled individual patient data from two prospective, population-based cohorts of patients with a first-ever ICH in the UK,¹ the authors identified lobar ICH as the principal risk factor for recurrent ICH and comorbid AF as the principal risk factor for ischemic stroke and all serious vascular events. Of interest, when putting hematoma location and AF together, they showed that risk of recurrent ICH would outweigh the risk of ischemic stroke only for patients with lobar ICH who did not have comorbid AF, highlighting the importance of reducing risks of thromboembolic events if we were to reduce overall risks of stroke burden after ICH. This echoed with findings from another study in the US which found that ICH was associated with an increased risk of ischemic stroke and myocardial infarction compared to patients without ICH.²

It is perhaps not surprising that patients with ICH were at high risk of ischemic events. In the UK study, one out of five patients had comorbid AF, and one out of three patients reported a history of previous occlusive vascular disease.¹ Consequently, at the time of the ICH, half of the patients were on antithrombotic medication treatment, with a third of antithrombotics being anticoagulant drugs, while a third of the patients were on statin treatment.¹ However, most of the patients had their antithrombotic drugs stopped after the ICH.

What should we do about these patients who not only have high risk of recurrent ICH but also high risk of ischemic events?

The Restart or Stop Antithrombotics Randomised Trial (RESTART)³ has been pivotal in trying to answer the question on resuming vs. stopping antiplatelet agents after an ICH. Treatment strategies regarding the cessation vs. (re-)start of antithrombotic medications especially anticoagulants or statins after an ICH are also currently being explored by numerous ongoing randomized controlled clinical trials. In addition to available treatment options there is also an unmet need for novel therapeutic approaches that can ameliorate the thromboembolic risk without increasing the risk of re-bleeding in ICH survivors, especially during the early stages after the ICH ictus. Clotting vs. re-bleeding, we still have many hurdles to overcome before we know the answer.