Strengthening early DOAC support after AF-related stroke

Abu Dhabi, United Arab Emirates — the next day Two new datasets While doubts seemed to be dispelled that essentially all atrial fibrillation (AF) patients should receive direct oral anticoagulants (DOACs) immediately after an acute stroke, the very same message was echoed by last year's breakthrough Powered by a new risk-weighted analysis of major trials.

For those still concerned about iatrogenic bleeding events with early DOAC use, “we would like to argue that our findings essentially eliminate any net harm from early initiation of anticoagulation,” said the study director. said Dr. Alexandros A. Polymeris, MD, Neurology and Stroke Center. , University of Basel, Basel, Switzerland.

The results were published in the latest study on October 25th. 16th World Stroke Congress (WSC) 2024.

The best way to reduce complications

Just over a year ago, 2000 patients ELAN trialwas published in of New England Medical Journalthe net benefit of early DOACs, defined as within 28 hours of AF-related stroke, compared with late DOACs, variably defined as 3-4 days after mild stroke and 6-7 days after moderate stroke. It was confirmed. 14 days after a major stroke.

Net benefit was based on a composite event list of ischemic stroke, systemic embolism, major extracranial hemorrhage, symptomatic intracranial hemorrhage, or vascular death. At 30 days, primary outcome events were less frequent with early than late DOACs (2.9% vs. 4.1%), but the 95% CI includes a 0.5% increase in event risk, and events were equally treated.

Treating these events equally is a problem, Polimeris said. In particular, it does not exclude the possibility of an increased risk of the most catastrophic events.

“We all know that these events [included in the composite endpoint] are not equivalent. They are not equally deadly. They’re not disabling in the same way,” he said.

This was the premise of ELAN's new post-hoc analysis, conducted for those who remain concerned that early DOACs may increase the risk of the most serious complications after stroke.

In this post hoc analysis, specific events were given weight. Using weighting to reflect the relative risk of serious harm, this study found that for early and late DOAC therapy within the 95% interval, not only did the risk of all types of events decrease, but there was also a net reduction in serious harm. We were able to show that there is no possibility of an increase.

This finding was fully consistent with the CATALYST meta-analysis of four major studies, including the randomized OPTIMAS study of 3468 patients and ELAN, which addressed this question. OPTIMAS and CATALYST are both Sequential presentation Just one day ago at WSC.

In remarks after the plenary session in which the OPTIMAS trial and CATALYST meta-analysis were presented, session moderator Craig Anderson, MD, of the George Institute for Global Health in Sydney, Australia, called the results “a change in practice.” I expressed it.

In contrast to some guidelines that suggest later initiation of DOACs after AF-related stroke is better than earlier initiation, he said, accumulating data suggest that starting DOACs after AF-related stroke may reduce post-stroke complications. suggested that early initiation of DOACs was established as the best way to treat the disease.

Risk of intracranial hemorrhage (ICH) must not overshadow net benefits

The data presented by Polymeris makes this story even more convincing. Despite the randomized trial, doubts could still linger if the most serious consequences were not given weight, he noted.

In other words, this new analysis shows that the increased risk of ICH or bleeding is more than compensated by the reduced risk of thrombotic events based on outcomes such as disability and death.

Many clinicians recognize that “ICH is known to carry a much higher risk of disability and death than mild stroke or systemic thromboembolism,” Polymeris said. For this reason, he and his collaborators undertook a comprehensive weight-based analysis.

The net benefit analysis was derived from the outcomes of 958 patients randomized to early DOACs and 959 patients randomized to late DOACs in ELAN. There were no significant differences in baseline characteristics. Outcomes were evaluated at both 30 and 90 days.

Events were weighted according to the risk they caused, using published methodological formulas and adjusting for variables such as age, severity as measured by the National Institutes of Health Stroke Scale, and infarct size. For example, ischemic events were given a value of 1.0, extracranial hemorrhage, a lower risk event, was given a weighting of 0.7, whereas ICH, often the most feared complication, was given a weighting of 1.5. weights were given.

Considering these weighted risk equivalences, there is a consistent benefit for early DOACs after subtracting the proportion of excess major bleeding events attributable to early treatment from the recurrence rate of ischemic events prevented by early treatment. Polymeris reported that there was. This was true for both 30 and 90 days.

Expressing all events as ischemic event equivalents per 100 people, “early DOAC initiation is estimated to prevent 2 to 3 events,” Polymeris reported. Polymeris concludes that while a neutral effect is statistically unlikely when evaluated across the wide range of adjusted 95% CIs employed, the possibility of adverse effects from early DOACs is essentially ruled out. said.

Although current guidelines regarding the early use of DOACs are controversial, ELAN's post hoc analysis, together with new data from the OPTIMAS and CATALYST meta-analyses, supports the use of early DOACs as standard treatment for most patients with acute AF-related illnesses. has been established. According to Polymeris, stroke.

He acknowledged that exceptions should be considered for patients at particularly high risk of bleeding, but these conclusions apply to real-world practice.

Anderson also suggested in his talk that there may be exceptions, such as patients who are frail or have other risk factors for increased bleeding, but the combined results of OPTIMAS and CATALYST suggest that acute stroke It is said that the management of most patients with atrial fibrillation is convincing. .

Professor Anderson said the following day that, like Polymeris, these data should be reassuring to clinicians who have been reluctant to use DOACs initially after atrial fibrillation-related stroke for fear of ICH.

The ELAN study received funding from governments and nonprofit organizations. Polymeris reports no relevant financial relationships. Mr. Anderson reported financial relationships with Penumbra and Takeda China.