I. Background
As a common disease with increasing incidence year by year, atrial fibrillation and its complications have always been the focus of clinical prevention and treatment. Stroke due to atrial fibrillation affects the function of most brain tissues, and this type of stroke is more likely than other types to result in death or loss of self-care. Clinically, patients with atrial fibrillation are treated orally with long-acting anticoagulants to reduce the risk of stroke or systemic embolism.
Voices questioning the role of anticoagulants persist, mainly because of the increased risk of bleeding events associated with such drugs. Therefore, the choice of the appropriate anticoagulation regimen for the patient in clinical care is often a dilemma for physicians.
Current status of epidemiological studies
A recent study of the global incidence of atrial fibrillation suggests that the incidence of atrial fibrillation in the United States will be 3.5 times greater in the next 50 years than it is today, based on extrapolations from existing conditions. Cohort studies in North America and Europe indicate that the status of AF in these two regions is not encouraging, with approximately one quarter of the population likely to be at lifetime risk for AF. Recent studies have suggested that the incidence of AF is related to race.
Background and rationale for atrial fibrillation anticoagulation
The results of the Framingham cohort study were the first to suggest a correlation between atrial fibrillation and stroke. Early studies showed a 5-fold increased risk of stroke in patients with non-rheumatic AF compared with 17-fold in patients with rheumatic AF. Subsequent studies have focused on the causal link between AF and stroke.
The high incidence of left ear embolism in patients with atrial fibrillation is the more used theory to explain the link at this stage. Further it is due to atrial blood flow arrest after atrial fibrillation. On the other hand, there are also in vitro studies that point out that patients’ blood is in a hypercoagulable state after atrial fibrillation. Regardless of the cause, stroke in patients with atrial fibrillation does occur as a result of cardiogenic thromboembolism.
The relationship between atrial fibrillation and stroke has prompted a search for solutions to the problem. Several controlled clinical trials have shown that antithrombotic agents, including antiplatelet agents and anticoagulants, are effective in preventing stroke in patients with atrial fibrillation. At this stage of clinical care, patients are stratified according to stroke risk factors to maximize the benefits of anticoagulation while avoiding bleeding events that occur with anticoagulation.
IV. Early risk stratification
The Framingham cohort study showed an increased risk of stroke in patients with rheumatic atrial fibrillation, which may be due to rheumatic mitral stenosis.
The Framingham cohort study failed in its attempt to further stratify patients for risk.
V. Stroke risk score
The CHADS2 scoring system is commonly used clinically to assess stroke risk rates in patients with non-valvular lesions in atrial fibrillation. In this system, congestive heart failure, hypertension, age over 75 years and diabetes mellitus are each recorded as 1 point, and a history of stroke and transient ischemic attack are scored as 2 points. Many cohort studies have confirmed the good performance of this scoring system in stroke risk assessment.
When attempts were made to improve risk stratification in the CHADS2 low-risk patient group, the system did not apply to emerging risk factors. The resulting CHA2DS2-VASc further stratified for age and counted women or the presence of vascular disease as a score of 1. Follow-up studies demonstrated that the CHA2DS2-VASc improved the scoring in the low-risk score patient group.
However, the ability to discriminate between CHADS2 and CHA2DS2-VASc remains limited. This may be due to the relatively small sample size of the two scoring systems. CHA2DS2-VASc has improved the discrimination of low-risk scores, but its confidence intervals are controversial. Therefore, the guidelines indicate that a revision of the CHA2DS2-VASc will be made soon.
In conclusion, the main reason for these problems is the large variability in the pro-stroke effect due to risk factors. The “contribution” of the same risk factor varies across patient groups.
VI. Bleeding event score
Bleeding event scoring systems have been developed to weigh the pros and cons of bleeding against stroke. The most commonly used include the ATRIA, HAS-BLED, and HEMORR2HAGES scoring systems. These scoring systems cover a wide range of factors that may contribute to future bleeding events and have been validated in relevant cohort studies.
However, some of the risk factors in these scoring systems are difficult to measure, and no studies have shown a positive effect of forgoing anticoagulation in patients at high risk for bleeding events.
On the other hand, it is difficult to equate risk factors for bleeding events in patients with atrial fibrillation with contraindications to anticoagulation therapy. Moreover, these decisions depend heavily on individual subjective judgment. While the guidelines recognize the potential status of such scoring systems as tools, they also state that these scores alone should not be relied upon to exclude patients from anticoagulation therapy.
Although the presenting event scoring system intersects with the risk factors involved in stroke scoring systems, evidence at this stage points to a net clinical benefit for patients with the exception of those at high risk for bleeding events.
VII. Balancing risk factors
Although all anticoagulants may cause an elevated risk of presenting events, apixaban is the only one that has been validated by the AVERROES study as an effective and safe ideal alternative to warfarin. this was also confirmed by the ARISTOTLE study. Therefore, apixaban may be a good alternative for patients at high risk for bleeding events and for whom vitamin K antagonists are contraindicated.
On the other hand, dabigatran is the best treatment for patients at risk of ischemic stroke. Studies have shown that dabigatran is the only one of the three drugs that can reduce the risk of non-ischemic stroke.
However, patients at high risk of non-ischemic stroke also have a high risk of acute coronary syndrome, and studies have associated dabigatran with myocardial infarction, although the results of these studies are debatable and we should try to balance these factors.
VIII. Conditions requiring special consideration
10% of patients on dabigatran develop dyspepsia and a change in medication can eliminate the symptoms. Therefore, dabigatran should not be given to patients with dyspepsia, acid reflux, or gastrointestinal dysmotility disorders. Apixaban may be used in this case.
For some patients who cannot take the drug multiple times a day, rivaroxaban is the only alternative to warfarin that can be taken only once a day.
IX. Change of medication during treatment
For newer oral anticoagulants, it is not recommended to change the drug class easily. Because of the rapid onset of action of these drugs, the pharmacokinetics of which are identical to those of drugs such as low-molecular-weight heparin, there is little benefit in using low-molecular-weight heparin as a substitute for newer oral anticoagulants.
On the other hand, the use of new oral anticoagulants early in the postoperative period may be detrimental to the patient, whereas warfarin has a rapid onset of action and less impact on coagulation after a few days.
X. Management of bleeding events
Prevention of stroke in patients with atrial fibrillation must be prepared for the management of bleeding events. In patients on warfarin, blood products or vitamin K supplementation are often given based on clinical experience, with the former being used for emergencies and the latter having a slow onset but long-lasting effect.
There are no particularly effective preventive measures for bleeding events caused by new anticoagulants. Although some investigators believe that supplementation with coagulation factors may have some effect, there is a lack of sufficient studies to confirm this, and the possible thrombotic complications that may result from this approach could diminish its own antihemorrhagic effects.
XI. Summary
Thromboembolism is a major contributor to morbidity and mortality in patients with atrial fibrillation. Oral anticoagulants can provide benefits for patients at risk of stroke. On the other hand, we need to risk stratify patients to better improve drug safety and treatment outcomes. The bleeding event scoring system is in urgent need of further improvement.
The new oral anticoagulants represent a major breakthrough in clinical care, but their types and dosages need to be carefully considered. Although these drugs are effective in reducing intracranial hemorrhage, prevention and control of bleeding events in patients with atrial fibrillation remain important issues in clinical care. We must continue to improve our current bleeding event management protocols.