Atrial fibrillation

Introduction
Atrial fibrillation was initially associated with systemic embolism in cases of concurrent mitral valve disease, but in 1974 an association of atrial fibrillation of any etiology and stroke were determined.

Marker of atrial cardiopathy
Atrial fibrillation itself may be an epiphenomenon, and a marker of underlying atrial cardiopathy. In the ASSERT trial, atrial fibrillation was found in 18 of 51 patients who had an ischemic stroke or systemic embolism, but in only 4 patients (8%) was atrial fibrillation detected within 30 days of the embolism and in only 1 of these 4 patients was atrial fibrillation detected at the time of the stroke. In the other 14 patients with ischemic stroke and atrial fibrillation, the most recent episode occurred at a median interval of 339 days (IQR 211-619 days). Similarly, in the TRENDS study, 40 patients had ischemic stroke or systemic embolism. Of those, 20 (50%) had atrial fibrillation detected prior to the event, but only 11 of these (28%) had atrial fibrillation detected in the 30 days prior to the event. The absence of a temporal association calls into question the causative nature of atrial fibrillation in ischemic stroke.

Risk factors

 * Age (older)
 * Congestive heart failure
 * Coronary artery disease
 * Hypertension
 * Obesity
 * Peripheral vascular disease
 * Valve disease

HAVOC score (2017)
This score was developed to predict the incidence of atrial fibrillation after stroke. It used ICD-9 codes for diagnoses and was both derived and validated retrospectively in the same publication with a total of 9,589 patients in a database. It had an AUROC of 0.77. A validation study in 214 patients from the CRYSTAL AF study showed that even among low risk patients (HAVOC score 0-1), 10.6% had atrial fibrillation with long-term monitoring. Of those with a score of 2-3 18.3% had atrial fibrillation, and for >3 31.8% had atrial fibrillation. The study had very few patients with scores ≥ 5. Thus the "low risk" group originally defined (HAVOC 0-4) appears to not be very low risk when monitoring is prolonged. It was also studied in a database of 658 ESUS patients. They found that the risk of AF in patients with a HAVOC score of 0 was 4.3%, with 0-4 was 11.3%, and ≥ 5 was 28.8%. Therefore the originally proposed HAVOC score underestimated the risk of atrial fibrillation in the "low risk" group, which is problematic. It had an AUROC of 0.69, whch was lower than the original publication. Thus this score is probably not very useful, as even low risk patients should be monitored for atrial fibrillation.

AS5F score (2019)
This score was developed and validated in 1,556 patients included in three prospective studies, and uses logistic regression. It has not yet been externally validated, however.

Various calculations have been worked out in the table below for easy reference. An online calculator is available here.

Long term monitoring
30-day or longer cardiac monitoring detects more atrial fibrillation and leads to more anticoagulation being used. However, its effect on stroke prevention itself remains unclear.

30-Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation after a Cerebral Ischemic Event (EMBRACE, June 2014)
This trial randomized 527 patients with age ≥ 55 who had a cryptogenic ischemic stroke or TIA within 6 months to undergo a 30-day event-triggered cardiac recorder or a conventional 24 hour monitor. They discovered atrial fibrillation lasting 30 seconds or longer in 16.1% of the 30-day monitoring group compared with 3.2% in the control group, representing a number needed to screen of 8. Atrial fibrillation lasting 2.5 minutes or longer was noted in 9.9% of the intervention group compared with 2.5% of the control group, representing a number needed to screen of 13.5. These results significantly increased the rate of anticoagulation in the intervention group compared with controls (18.6% vs 11.1%).

Cryptogenic Stroke and Underlying AF (CRYSTAL AF, September 2014)
This trial randomized 441 patients with age ≥ 40 who had a cryptogenic ischemic stroke to either an insertable cardiac monitor or conventional follow-up. By 6 months they had detected atrial fibrillation in 8.9% of patients in the implantable monitor group vs. 1.4% of patients in the control group, for a number needed to screen of 13. By 12 months atrial fibrillation had been detected in 12.4% of the implantable monitor group vs. 2.0% of patients in the control group, for a number needed to screen of 10. Ischemic stroke occurred in 7.1% of patients in the implantable monitor group compared with 9.1% of patients in the control group within one year, although the difference was not statistically significant.

Other data
In a cohort of 9,589 ischemic stroke patients, 482 were found to have atrial fibrillation. Of these, the majority were diagnosed more than a year after stroke onset (26.3% in 1-3 years, and 45.3% after 3 years).

Elderly patients
For elderly patients, DOACs are preferred. Apixaban has been shown to be of benefit for patients up to age 92, but after that may no longer be useful due to a competing risk of mortality. In a study of 11,662 survivors of acute ischemic stroke at median age 80 years (IQR 74-86), patients given DOACs did better than those given warfarin, with much more institution-free home time (aHR 15.6, 9.0-22.1), fewer major adverse cardiovascular events (aHR 0.89, 0.83-0.96), less mortality (aHR 0.88, 0.82-0.92), fewer readmissions overall (aHR 0.93, 0.88-0.97), less hemorrhagic stroke (aHR 0.62, 0.50-0.95), and less bleeding overall (aHR 0.89, 0.81-0.97). However, there were slightly more GI bleeds (aHR 1.14, 1.01-1.30). After age 87, there is probably minimal lifetime net benefit for anticoagulation with warfarin, but benefit continues up to age 92 with apixaban.

Benefits if a stroke occurs
A registry study suggested that patients on DOACs vs. VKAs at the time of ischemic stroke who underwent thrombectomy had better outcomes (90 day mRS 0-1, OR 2.40, 95% CI 1.10-5.27) and lower 90-day mortality (OR 0.47, 95% CI 0.24-0.89). Although retrospective which creates the possibility for confounders, DOACs may provide a benefit in patients even if they have a stroke if they undergo mechanical thrombectomy.

Risk of traumatic hemorrhage
In a retrospective series of 136 patients with traumatic intracranial hemorrhage (mostly subdural hematoma), those taking DOACs compared with those taking VKAs had higher rates of good outcome (GOS 4-5, 66.7% vs 40.2%, aOR 4.32, 95% CI 1.56-11.97) and higher rates of discharge to home or rehabilitation (74.4% vs 55.7%, aOR 6.30, 95% CI 1.98-20.10).

Elderly patients
Favor using DOACs for secondary stroke prevention from atrial fibrillation in the elderly. In a study of 11,662 survivors of acute ischemic stroke at median age 80 years (IQR 74-86), patients given DOACs did better than those given warfarin, with much more institution-free home time (aHR 15.6, 9.0-22.1), fewer major adverse cardiovascular events (aHR 0.89, 0.83-0.96), less mortality (aHR 0.88, 0.82-0.92), fewer readmissions overall (aHR 0.93, 0.88-0.97), less hemorrhagic stroke (aHR 0.62, 0.50-0.95), and less bleeding overall (aHR 0.89, 0.81-0.97). However, there were slightly more GI bleeds (aHR 1.14, 1.01-1.30).