Alejandro Rodríguez-Vázquez, MD

Du H, Wilson D, Ambler G , Banerjee G, Shakeshaft C, Cohen H, Yousry T, Al-Shahi Salman R, Lip GYH, Houlden H, et al. Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia. Stroke. 2021;52:91–99.

Atrial fibrillation (AF) is one of the most important risk factors associated with ischemic stroke, with a 4.7 to 7.7%/year risk of cerebrovascular events despite anticoagulation. These recurrences could be explained because of an inadequate anticoagulation or alternative stroke mechanisms such as small vessel disease (SVD).

The authors analyzed data from the CROMIS-2 study, a multicenter prospective inception cohort study of patients anticoagulated for AF after an ischemic stroke or transient ischemic attack. They included 1419 patients with MR imaging and a total follow-up of 24 months after the first cerebrovascular event. SVD was present in 768 (54.1%) patients, defined as the presence of ≥11 basal ganglia perivascular spaces (BGPV), ≥11 centrum semiovale perivascular spaces, cerebral microbleeds, lacunes and/or moderate to severe white matter hyperintensities (which included periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2).

The ischemic stroke rate in patients with SVD was 2.20 per 100-patient years (95% CI, 1.60–3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59–1.62) in those without SVD presence, and a higher SVD score was also associated with an increasing risk of recurrent cerebrovascular events during follow-up (HR per point increase, 1.45 [95% CI, 1.14–1.83]; P=0.002). After adjusting by confounders such as CHA₂DS₂-VASc score, therapeutic time in range in vitamin K antagonist-treated patients, carotid-artery stenosis, and antihypertensive and statin treatment, SVD still remained as an independent risk factor for ischemic recurrence. Analyzing SVD components separately, the presence of ≥11 BGPV was the one with the highest risk (2.98 per 100-patient years [95% CI, 1.99–4.44], compared with 1.18 per 100 patient-years [95% CI, 0.82–1.70] in those with 0 to 10 BGPVS) and the only statistically significant after adjusting for CHA₂DS₂-VASc score as a single confounder. Finally, although there were no significant differences in baseline SVD among different stroke mechanisms, the absolute rate of recurrent small artery occlusion in patients with SVD was higher than in those without it (7.9% versus 0%).

The results of this study point to that AF is not necessarily the exclusive cause of an ischemic stroke recurrence in stroke patients with AF, since AF commonly coexists with other potential etiologies such as SVD or large carotid atherosclerosis. There is data from studies like ORBIT-AF, ROCKET-AF and ARISTOTLE which do not support combining antiplatelet treatment with standard-dose anticoagulation for stroke prevention in patients with AF. On the other hand, COMPASS and PIONEER-AF-PCI suggested that antiplatelet therapy added to low-dose rivaroxaban could be reasonable in terms of efficacy and safety in patients with AF and atherosclerotic cardiovascular disease. In any case, identifying the most probable source of ischemia is key in choosing the best prophylaxis. SVD burden, independently of AF, is a marker that could help us clinicians to understand the individual pathophysiology of each patient’s stroke so we can offer the best treatment. In that sense, this group of patients with AF and SVD should be the focus for new prevention trials and strategies.