Letter to the editor Cerebral small vessel disease may be related to antiplatelet-induced gastrointestinal bleeding Dear editor, Aside from central nervous system bleeding, gastrointestinal bleeding (GIB) is a major complication of antiplatelet therapy in stroke patients. A long duration of dual antiplatelets (vs. monotherapy) appears to be a factor leading to increased GIB (1). However, factors related to GIB in patients receiving antiplatelets remain uncertain. Cerebral small-vessel disease (SVD) manifests as lacunes, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds (2). Recent studies have provided evidence that patients with cerebral SVD may have widespread vasculopathy in other organs as well (3), although the clinical expression may be purely neurological. We hypothesized that patients with cerebral SVD may more often develop GIB. We studied patients with cerebral infarction who developed GIB while receiving antiplatelet therapy between May 2007 and May 2013 in a tertiary hospital. Age-and sex-matched control subjects who did not experience GIB were Correspondence: Jong S. Kim*, Department of Neurology, Asan Medical Center, University of Ulsan, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Korea. E-mail: [email protected] Conflict of interest: None declared. DOI: 10.1111/ijs.12345

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Table 1 Multivariate analysis for gastrointestinal bleeding risk

Small-vessel disease White matter hyperintensity Lacune Perivascular space Microbleeds

Odds ratio

95% CI

P-value

4·251 3·324 2·382 4·267 2·026

1·323–13·66 1·273–8·68 1·074–5·283 1·796–10·134 0·779–5·269

0·02 0·01 0·03 0·001 0·34

The variable was selected if the significance level was over 20% in the univariate analysis of each model.

randomly selected from patients attending the outpatient clinic on the same day as the study subjects. Patients receiving anticoagulants were excluded. Brain magnetic resonance images were evaluated for the presence of SVD markers: lacunes, white matter changes, microbleeds, and perivascular spaces. Forty-six patients with GIB and 92 control subjects were enrolled. Between the two groups, no differences were found for the demographic characteristics, vascular risk factors, stroke subtypes, or number of antiplatelets (monotherapy vs. dual therapy). The prevalence of white matter hyperintensities (P = 0·01), lacunes (P = 0·01), and perivascular spaces (P < 0·001) was higher in the GIB group than in control subjects. To avoid multicollinearity among white matter hyperintensities, lacunes, perivascular spaces, and microbleeds, each marker of SVD and SVD itself was individually included in the multivariable analysis, which showed that SVD, white matter hyperintensities, lacunes, and perivascular spaces were independently associated with an increased GIB (Table 1). Our findings suggest that stroke patients with cerebral SVD may have an

increased risk of antiplatelet-associated GIB. This may be related to the systemic small vessel pathology in these patients. We may have to be more cautious in choosing the number and dose of antiplatelets in patients with extensive SVD. Further studies with a larger number of patients are required to confirm our preliminary findings. Sang Mi Noh, Bum Joon Kim, and Jong S. Kim* Department of Neurology, Asan Medical Center, University of Ulsan, Seoul, Korea

References 1 Diener HC, Bogousslavsky J, Brass LM et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004; 364:331–7. 2 Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013; 12:483–97. 3 Thompson CS, Hakim AM. Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis. Stroke 2009; 40:e322–30.

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