Managing antithrombotic treatment in a patient with atrial fibrillation and coronary stent with transient neurological symptoms in cerebral amyloid angiopathy

Abstract

We present the antithrombotic dilemma in a case with atrial fibrillation and a coronary stent and suspected transient ischemic attacks after diagnosed as a probable cerebral amyloid angiopathy and discuss plausible treatment options for the patient based on the available evidence.

Short abstract

Cerebral microbleeds seen in cerebral amyloid angiopathy are not only markers of bleeding tendency but also markers of future ischemic events. Patients with atrial fibrillation should have stroke prevention irrespective of their cerebral microbleeds.

1. INTRODUCTION

Cerebral amyloid angiopathy (CAA) is an age‐related small‐vessel disease characterized by β‐amyloid deposits in the walls of leptomeningeal and cortical blood vessels leading to symptomatic lobar intracerebral hemorrhage (ICH), as well as smaller bleedings including numerous cerebral microbleeds (CMBs) and cortical superficial siderosis. ¹ Typical CAA features include cognitive impairment and transient focal neurological episodes (TFNEs), also called amyloid spells, which are brief disturbances in motor, somatosensory, visual, or language functions that often mimic transient ischemic attacks (TIAs). ²

In this report, we present a case of a 71‐year‐old man with atrial fibrillation (AF) and a coronary stent in well‐regulated warfarin therapy. He was diagnosed as a probable CAA with numerous CMBs and TFNEs that mimics TIAs. We present the antithrombotic dilemma and discuss plausible treatment options for the patient.

2. CASE PRESENTATION

A 71‐year‐old male patient with a history of a left anterior descending artery (LAD) stent, hypertension, hypercholesterolemia, and paroxysmal AF treated with warfarin.

The patient was referred to a neurologist with suspected TIA after two episodes of aphasia, one lasting a couple of minutes and the other 1 h. Magnetic resonance imaging (MRI) of the cerebrum revealed moderate ischemic white matter hyperintensities of presumed vascular origin, along with numerous CMBs restricted to lobar cortical–subcortical regions (Figure 1). Based on the MRI findings, age over 55 years, and absence of other cause of hemorrhage, the diagnosis was probable CAA according to the modified Boston Criteria. ¹ Captopril was started to further reduce the patient's blood pressure with a target blood pressure below systolic blood pressure of 140 mmHg and diastolic blood pressure of 90 mmHg, and the well‐regulated warfarin treatment (time in therapeutic range: 80%–88%) was continued.

FIGURE 1.

MR imaging showing multiple cerebral microbleeds (CMBs). Multiple CMBs restricted to lobar cortical–subcortical regions on a susceptibility‐weighted imaging sequence at the level of the basal ganglia (A) and corona radiata (B).

Subsequently, the patient was admitted to the emergency department due to sudden dysesthesia, blurred vision, dizziness, and headache, which remitted after 2 h. The INR was 3.0. Neurological examination revealed slightly reduced left hand motor function. The patient underwent stroke work‐up, which was unremarkable, and he was referred to the thrombosis clinic to further optimize the antithrombotic treatment.

3. DISCUSSION

Hemorrhagic and ischemic manifestations occur frequently in CAA and cause management dilemmas. ³ , ⁴ A presenting feature of CAA may be a TFNE, which may be difficult to distinguish from TIAs. CAA‐related TFNEs can be an initial sign for a high risk of future ICH. ² Therefore, it is important to differentiate TFNE from TIA, and MRI can therefore be useful in patients eligible to thrombolysis. The patient described in this report presented with transient, self‐resolving two episodes of aphasia and later one episode of upper extremity weakness. These symptoms were initially interpreted as TIAs. However, the diagnosis of CAA with the aid of appropriate imaging and the well‐regulated warfarin treatment of the patient for AF suggested that these symptoms are most probably due to TFNE and unlikely to be related to TIA. This assessment is done after the acute course, which also explains why the patient was not considered to be subscribed steroid initially as a treatment for neurological symptoms, but instead treated according to the national guidelines for TIA. It is also important to note that steroid treatment is indicated in CAA‐related inflammation (CAA‐ri), which appears to represent a distinct manifestation of CAA characterized by an inflammatory response to amyloid deposition in the brain with subacute neurologic symptoms. ⁵ The most common presenting symptoms of CAA‐ri are cognitive decline, seizures, and headache. ⁵ These were not the main symptoms for the patient and therefore CAA‐ri diagnosis was not considered for the patient and steroid treatment was not initiated in the subacute period, either.

The patient in this case report had comorbid not only AF, but also a LAD stent, which was placed in 2017 after uncomplicated percutaneous coronary intervention, making the anticoagulation treatment complicated. The risk of ischemic stroke in patients with AF can be up to 20% annually. ⁶ In CAA patients, the risk of ICH varies by phenotype and is highest in patients with TFNEs (24.5% at 2 months) ² , ⁷ and lowest in patients with isolated numerous CMBs (4% annually). ⁸ In the absence of randomized trials, clinicians should consider the risk–benefit of anticoagulation for each patient individually. ³ CHA₂DS₂‐VASc and HAS‐BLED scores were used to assess the risk–benefit in the current case. The patient had a HAS‐BLED score of 3 (hypertension [1 point], age [1 point], and bleeding tendency due to numerous CMBs [1 point] [3.7% risk of bleeding per year]) and a CHA₂DS₂‐VASc score of 3 (hypertension [1 point], age [1 point], and vascular disease [1 point] since the patient has coronary stent [3.2% risk of ischemic stroke per year]) with proviso that the neurological symptoms of the patient were due to TFNEs and not TIA. In the case of the patient's neurological symptoms was assessed as TIA (2 point); instead, the CHA₂DS₂‐VASc score would be 5 (6.7% risk of ischemic stroke per year). However, these scores do not accurately account for CAA in patients with AF, and the risk of ICH may be higher than the HAS‐BLED scores predict. ⁹ Taking into consideration both the patient's additional ICH risk of about 24.5% at 2 months due to the CAA–related TFNEs ² , ⁷ and 4% annually due to the numerous CMBs ⁸ and the HAS‐BLED score prediction (3 points), one could assume that anticoagulants might cause net harm. Supporting this assumption, the 2016 guidelines for the management of AF from the European Society of Cardiology suggested that anticoagulation treatment for stroke prevention in AF should not be considered in patients with probable CAA. ¹⁰ According to the recent NAVIGATE ESUS trial, ¹¹ however, CMBs are not only markers of bleeding tendency but also markers of future ischemic events. Similarly, the CROMiS‐2 study ¹² showed that ischemic stroke in patients with CMBs was much more common than ICH. The growing evidence from the recent studies suggests persistent benefit from anticoagulation treatment of patients with AF and CMBs. ¹¹ , ¹² In the current case, therefore, the combination of AF, the ischemic stroke risk, and an LAD stent means, that discontinuing warfarin without further actions would be inappropriate. Considering the patient's CHA₂DS₂‐VASc score of 3 or 5 (if the patient's neurological symptoms were assessed as TIA) in the setting of AF, a switch from warfarin to aspirin would also be inappropriate. The CROMiS‐2 study further demonstrated that in patients with CMB, the presence of a high HAS‐BLED score and warfarin rather than direct oral anticoagulant (DOAC) increase ICH risk in patients with AF. ¹² Of particular note is the recent meta‐analysis ¹³ suggesting that CMBs are related to warfarin treatment, but not DOAC, and that CMBs increase the risk of warfarin‐associated ICH. Therefore, the continuation of warfarin would also be inappropriate, despite the well‐regulated warfarin treatment.

Compared to warfarin, DOACs show similar or reduced risk of ischemic stroke with less ICH. ¹⁴ After all these considerations, we concluded that our patient with AF should continue stroke prevention irrespective of his CMB and TFNE profile with DOAC. As the AVEROS study ¹⁵ showed that apixaban reduced embolic infarctions in AF patients without increasing the number of CMBs, the patient's warfarin was switched to apixaban, initially as a half‐dose (2.5 mg × 2) after interpreting the patients neurological symptoms most probably as CAA‐related TFNE, which is associated with the high risk of symptomatic ICH of 24.5% at 2 months. ² , ⁷ This decision was later revaluated in a multidisciplinary meeting, and the apixaban was increased to 5 mg × 2. This was due to the presence of the LAD stent, the much more common presentation of ischemic stroke in patients with CMBs than ICH ¹¹ , ¹² and the association of off label underdose DOAC use with higher risk of all‐cause mortality and cardiovascular composite outcome in AF patients. ¹⁶

4. PATIENT OUTCOME

After switching from warfarin to apixaban, the patient has not experienced any symptoms suggesting TIA, TFNE, or ICH in the last 6 months. The diagnosis of CAA coupled with the decision of long‐term apixaban treatment increases the risk of ICH in the long‐term. After discussion of the patient's preferences and concerns, he has been referred to left atrial appendage closure, as a treatment option for AF.

AUTHOR CONTRIBUTIONS

Julie Ravn performed the literature review, interpreted the data, and wrote the first draft of the manuscript and approved the final manuscript. Tobias Sejbæk interpreted the data, helped to write the manuscript, and approved the final manuscript. Mustafa Vakur Bor planned the study, supervised for the recruitment of the subject, interpreted the data, and helped to write the manuscript, and approved the final manuscript.

FUNDING INFORMATION

This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors.

CONFLICT OF INTEREST

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

CONSENT

The patient is aware that his clinical details are used in this paper. Written consent was given by the patient and was not subject to special conditions.

Ravn J, Sejbæk T, Bor MV. Managing antithrombotic treatment in a patient with atrial fibrillation and coronary stent with transient neurological symptoms in cerebral amyloid angiopathy. Clin Case Rep. 2022;10:e06624. doi: 10.1002/ccr3.6624

DATA AVAILABILITY STATEMENT

Data available on request due to privacy/ethical restrictions.