Page 33 - BH-2-3

Brain & Heart Digital tools for stroke and bleeding risk in AF

HAS-BLED features a warfarin-specific variable: 5. Recent guideline updates
labile INR. When “time in therapeutic INR range,” a
variable inversely related to labile INR, was added to the Current guidelines from the European Society of
ATRIA and ORBIT scores, their predictive performance Cardiology/European Association for Cardio-Thoracic
improved. This evidence highlights the importance of Surgery/European Heart Rhythm Association (ESC/
65
considering labile INR and/or time in the therapeutic EACTS/EHRA) in 2020 and the Asia Pacific Heart
INR range when assessing bleeding risk in patients with Rhythm Society (2021) recommend the CHA DS -VASc
2
2
AF receiving warfarin. However, DOACs, including score for estimating stroke risk and the HAS-BLED score
rivaroxaban, apixaban, edoxaban, and dabigatran, are for assessing bleeding risk in the setting of AF. 67,68 The
increasingly prevalent. Since the data used to create the 2023 AHA/ACC/ACCP/HRS guidelines for the diagnosis
aforementioned scoring systems for estimating bleeding and management of AF, which represent the newest society
risk is mostly derived from cohorts of patients with AF guidelines for managing AF to date, note that the risk of
on warfarin, these may not reflect patients’ true risk of stroke can be characterized as low (<1%/year), intermediate
bleeding while on DOACs. (1 – 2%/year), or high (>2%/year) and that the use of a
validated clinical risk score such as CHA2DS2-VASc, ATRIA,
To address this issue, a novel DOAC score was or GARFIELD-AF can do the calculation of this risk. They
30
introduced in 2023. Developed from individuals in both do not endorse a specific risk score. The recommendation
the Randomized Evaluation of Long-Term Anticoagulation to pursue anticoagulation therapy is made based on the
Therapy (RE-LY trial) and the GARFIELD-AF registry, annual percent risk of thromboembolism rather than the
the DOAC score includes 10 different risk factors that point summation of a specific risk score. Anticoagulation
were each assigned a specific number of points. One point therapy for patients with ≥2% annual thromboembolic
each is given for underweight, stroke/TIA/embolism risk (Class I recommendation) is recommended and
history, hypertension, diabetes, and non-steroidal anti- considered reasonable for patients with 1 – 2% annual
inflammatory use. Two points are awarded for liver disease, thromboembolic risk (Class IIa recommendation).
30
and 3 points if the individual has a history of bleeding. For Patients with AF who fall into the intermediate annual
the risk factors of age, creatinine clearance/glomerular risk category of thromboembolic events (<2%) may still
filtration rate, and antiplatelet use, different point values are benefit from consideration of additional factors that could
assigned based on specific categories within each factor. For potentially affect their risk of stroke. These factors include
example, within age, 2 points were given for 65 – 69 years, a higher AF burden, obesity, hypertrophic cardiomyopathy,
3 points for 70 – 74 years, 4 points for 75 – 79 years, and 5 poorly controlled hypertension, impaired kidney function
points for ≥80 years. One point is awarded if the individual (GFR <45 mL/h), proteinuria (>150 mg/24 h), and left atrial
has a creatinine clearance/glomerular filtration rate of 30 enlargement (volume ≥73 mL or diameter (≥4.7 cm). Direct
– 60 mL/min and 2 points if ≤30 mL/min. For antiplatelet oral anticoagulants (DOACs) such as apixaban, dabigatran,
use, aspirin use is assigned 2 points, while dual-antiplatelet edoxaban, and rivaroxaban are first-line medications and
therapy is assigned 3 points. The score classifies patients are preferred over warfarin to reduce the risk of mortality,
into risk categories of very low (0 – 3 points), low (4 stroke, systemic embolism, and intracranial hemorrhage
– 5), moderate (6 – 7), high (8 – 9), and very high (≥10 (Class I recommendation), except in patients with mitral
points) risk. The DOAC score was externally validated in stenosis or mechanical heart valves. The guidelines also
the COMBINE-AF and RAMQ cohorts, where it also had emphasize the need to examine drug interactions between
stronger predictive performance than HAS-BLED for major DOACs and other medications, namely inhibitors and
bleeding. Several factors have been hypothesized to explain inducers of CYP3A4 and p-glycoprotein.
66
the improved predictive performance of the DOAC score.
First, it assigns a different number of points to each variable Concerning the bleeding risk scores, the 2023 AHA/
rather than an equal point to each, reflecting the different ACC/ACCP/HRS guidelines recommend using them as part
magnitudes of bleeding risk for each variable. Second, it of the comprehensive clinical assessment of patients with
assigns a higher cumulative risk for those taking multiple AF and as guidance to determine modifiable risk factors to
antiplatelet/anticoagulant medications, whereas previous reduce a patient’s bleeding risk. Specifically, the guidelines
scores treated those with any combination of NSAIDs, note that unless there is an absolute contraindication to
aspirin, and dual antiplatelet therapy as having similar anticoagulation, the bleeding risk scores have limitations
risks. Third, it accounts for differences in the propensity in clinical guidance. Bleeding risk scores must not be
for bleeding at different levels of kidney function. Fourth, interpreted in isolation, as they do not balance the risk of
it was developed for a contemporary population, reflecting bleeding against the risk of stroke or provide an assessment
current standards of care and DOAC use. of the net clinical benefit of using anticoagulation. In the
30

Volume 2 Issue 3 (2024) 10 doi: 10.36922/bh.3068