OAC, AF, and Recurrent Stroke Risk: New Data

Despite secondary prevention with oral anticoagulation (OAC), the risk for recurrent ischemic stroke (IS) and mortality is high in patients with atrial fibrillation (AF). However, OAC discontinuation doubled the risk for recurrent IS compared with those who continued on blood thinners, new research showed.

Investigators in Denmark studied more than 8000 patients with AF and IS who were initiating or restarting OAC treatment. Those with a recurrent IS were compared with matched patients receiving OAC who had an IS. All patients were followed for a mean of 3 years.

Of those taking OACs who sustained a recurrent stroke during the study, 80% were taking currently OACS. However, those who discontinued OAC doubled the risk for recurrent IS compared with those who continued OAC.

“This finding highlights the importance of OAC continuation and the need for improved secondary stroke prevention in patients with AF,” the investigators, led by Mette Foldager HIndsholm, MD, of the Department of Neurology, Aarhus University Hospital, in Aarhus, Denmark, wrote.

The study was published online on June 24 in JAMA Neurology.

Substantial Residual Risk

OAC in patients with AF is guideline-recommended and reduces the risk for IS, the researchers noted. However, a “substantial residual risk” for IS remains, despite OAC treatment.

While previous studies have examined this increased risk prior to the index IS, few have specifically focused on OAC discontinuation and the risk for IS recurrence. To assess the incidence of IS recurrence in patients with AF receiving OAC, describe the characteristics of patients with recurrent IS, and evaluate the risk for recurrent IS associated with OAC discontinuation, the investigators used Danish registries to identify a cohort of patients with AF who were admitted for IS and then treated with OAC. The first admission for IS during the study period (January 2014-December 2021) was considered the “entry IS,” while IS during the follow-up period (until June 2022) was considered “recurrent IS.”

Cases were patients within the study who had recurrent IS during follow-up, and each was compared with four controls matched by calendar year and time since entry IS within 3 months. The comparison was adjusted for several comparisons, including age, sex, marital status, smoking, calendar year, and time since entry IS.

Severity on admission was compared by the grouped Scandinavian Stroke Scale (SSS) score and mortality of recurrent IS cases in discontinued OAC vs those with continued OCC use.

The final cohort consisted of 8119 patients (54.1% men; mean [SD] age, 78.4 [9.6] years; median [interquartile range] CHA₂DS₂-VASc score, 4.0 [3.0-5.0]). Patients were followed for a mean (SD) of 2.9 (2.2) years.

During follow-up, 663 patients had recurrent IS. Of these, 80.4% were taking OAC at the time of their recurrent IS.

At 1 year, the crude cumulative incidence of recurrent IS and all-cause mortality were 4.3% (95% CI, 5.9%-7.1%) and 15.4% (95% CI, 14.7%-16.2%), respectively. The researchers found similar results in the adjusted analyses.”

Patients who discontinued OAC had an almost twofold higher risk for recurrent IS than patients still receiving OACs. They also had more severe strokes and higher mortality rates.

“We found that recurrent IS was common,” the researchers wrote. “Prior IS and OAC discontinuation were associated with higher risks of recurrent IS and mortality, and OAC discontinuation was also associated with more severe recurrent IS and higher mortality rates.”

There was no information about the reasons patients discontinued OAC. “Reasons underpinning OAC discontinuation are at present poorly understood,” they wrote.

The investigators expressed concern that 80% of patients who had recurrent IS were still receiving OAC. They noted that they were “unable to rule out” nonadherence to the OAC restarters as a possible cause, but also noted that “no medication is 100% efficacious.”

The authors noted the study has several limitations. There might have been some underreporting of IS that cannot be ruled out. Moreover, only acute strokes are reported to the stroke registry, so patients with milder symptoms might not be captured, “leading to a potential underestimation of mild strokes in the registry.” In addition, data on alcohol intake and socioeconomic information were not included as potential confounders. Finally, the Danish study population was of largely European ancestry, so the results may not be generalizable to other populations.

The investigators concluded by encouraging investigation of “alternative secondary prevention strategies” such as left atrial appendage occlusion with or without continuous OAC in these high-risk populations.

No specific source of funding was listed. Hindsholm reported grants from C.B. Holding, Aarhus, during the conduct of the study. The other authors’ disclosures are listed in the original paper.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape Medical News and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom(the memoir of two brave Afghan sisters who told her their story).