Despite progress achieved in medicine, stroke remains a severe threat to life. The risk of this often fatal pathology sharply increases in patients with atrial fibrillation (AF), which in turn promotes the formation of thrombi. These thrombi, if they reach the brain, block the blood flow.
On the other hand, atherosclerosis (the appearance of fatty deposits in the walls of the arteries) increases the risk of stroke because, along with narrowing the blood vessel lumen, it activates the thrombotic cascade.
The standard approach to prevent stroke caused by AF involves the use of oral anticoagulants (OACs), which aim to prevent intracardiac thrombosis. And in individuals with atherosclerosis, antiplatelet medications (e.g., aspirin) are typically used to reduce the risk of stroke by inhibiting thrombus aggregation on plaques.
When these two pathologies coexist, doctors face a complex dilemma: how to prevent stroke without increasing the risk of bleeding? Current recommendations do not provide clear guidelines for solving this issue.
The ATIS-NVAF Study:
Due to the existing uncertainty, it became necessary to determine which antithrombotic strategy would bring real clinical benefit in these high-risk patients. The ATIS-NVAF study partially resolves this therapeutic dilemma.
The study’s goal is to evaluate which antithrombotic regimen is superior. It compares OAC monotherapy with its combination with antiplatelet agents. The research focuses on the prevention of recurrent cerebral ischemia in patients with non-valvular atrial fibrillation (NVAF) and atherosclerotic cardiovascular disease (ASCVD).
The ATIS-NVAF study was conducted in 41 centers in Japan. It included 316 patients who had recently suffered a cerebral ischemic event (stroke or transient ischemic attack – TIA) and were simultaneously diagnosed with NVAF and ASCVD.
Patients were randomly divided into two groups:
OAC monotherapy (anticoagulant only).
OAC combined with an antiplatelet agent.
The antithrombotic agents and their doses were individually prescribed by the treating physicians, reflecting real clinical practice. Prospective observation of the patients continued for two years; monitoring was carried out for recurrence of cerebral ischemia, cardiovascular events, and hemorrhagic complications.
Study Results:
When comparing the overall frequency of ischemic cardiovascular events and severe bleeding, no sharp clinical difference was found between the two groups.
The rate for combined therapy was 18%.
In the case of OAC only, the rate was 20%.
However, combined therapy noticeably increased the risk of bleeding:
The frequency of severe bleeding in the combined therapy group was 9.4%, versus 5.6% with monotherapy.
Furthermore, non-severe, but clinically significant, bleeding was recorded twice as often in the combined group.
Based on this data, bleeding was the main safety concern. Gastrointestinal and intracerebral hemorrhages dominated among the serious complications. The high frequency of bleeding was recorded on the background of dual antithrombotic therapy. This increased risk may outweigh the benefit of preventing embolism-related stroke.
Study Limitations:
The open-label design (where the treatment is known to both the doctor and the patient) may influence the reporting and management of side effects.
The individual selection of treatment (in terms of drugs and dosing) led to study heterogeneity.
Ultimately, the study’s results call into question the routine use of a combined antithrombotic regimen for secondary prevention of ischemic stroke in patients with NVAF and ASCVD. This finding will contribute to simplifying therapeutic protocols and improving patient outcomes.
Source: Jama Neurology
