Utrecht, the Netherlands—Anticoagulant management has been transformed by the availability of NOACs, which have been proven to be highly effective but do not require regular blood testing or special diets like warfarin.

But NOACs are not for everyone, and questions have been raised about the use of the drugs in frail patients with AFib managed with vitamin K antagonists (VKAs). A new study published in the journal Circulation looked at whether that cohort should be switched to NOACs.

Dutch researchers from the University Medical Center Utrecht and colleagues conducted a pragmatic, multicenter, open-label, randomized, controlled superiority trial. Researchers randomized older AFib patients living with frailty (aged 75 years or older with a Groningen Frailty Indicator [GFI] score of 3 or greater) to switch from international normalized ratio–guided VKA treatment to a NOAC or continued VKA treatment. Excluded were patients with a glomerular filtration rate <30 mL/min/1.73 m2 or with valvular AFib.

From January 2018 and June 2022, the study team screened 2,621 patients for eligibility and 1,330 patients were randomized. After additional exclusions, 662 patients switched from a VKA to a NOAC and 661 patients continued VKAs in the intention-to-treat population. Participants, who were followed for a year, had a mean age of 83 years and a median GFI of 4.

The researchers report that after 163 primary outcome events, including 101 in the switch arm and 62 in the continue arm, the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio (HR) for the primary outcome was 1.69 (95% CI 1.23-2.32). The HR for thromboembolic events was 1.26 (95% CI 0.60-2.61).

In assessing the FRAIL-AF Randomized Controlled Trial, the authors conclude, “Switching INR-guided VKA treatment to a NOAC in frail older patients with AFib was associated with more bleeding complications compared to continuing VKA treatment, without an associated reduction in thromboembolic complications.”

The researchers advise that switching from VKA treatment to NOAC treatment should not be considered in older AFib patients with frailty.

Because stroke prevention is the centerpiece of managing AFib, which is related to aging and comorbidity, patients are prescribed anticoagulants, either a vitamin K antagonist (VKA) or a NOAC, according to the report, which adds, “In newly diagnosed non-frail AF patients, NOACs are preferred over VKAs because in landmark trials NOAC treatment was associated with a lower risk of (major) bleeding at similar efficacy regarding stroke prevention, compared to VKAs.”

The authors point out, however, that a large population—an estimated 30% to 40%—of   older AFib patients remain on VKAs. “Many of these patients suffer from the frailty syndrome, a clinical entity of accumulating comorbidities and polypharmacy and defined by a high biological vulnerability, dependency on significant others and a reduced capacity to resist stressors,” they explain. “These AFib patients living with frailty, currently on VKA treatment, are managed mainly in an outpatient setting, close to the communities where they live, by family medicine specialists, cardiologists, or internists.  The high proportion of older AFib patients that are prescribed VKAs Instead of NOACs is a least partly attributable to the lack of convincing trial evidence on superiority of NOACs in older individuals with AFib living with frailty.”

The study team notes that previous studies on the impact of frailty on bleeding outcomes in AFib were largely observational because frail patients were underrepresented in the landmark trials.

“In daily practice, physicians will implicitly weigh multiple factors when deciding on the optimal anticoagulant treatment, which is very difficult to adjust for in observational studies,” the study explains. “Certainly, monitoring via International Normalized Ratio (INR) testing allows for intervening at an early stage by titrating the VKA dose to the most optimal range, which may be beneficial in older patients living with frailty given their larger volatility in anticoagulant status. Consequently, it is uncertain whether the superiority of NOACs over VKAs in AFib patients observed also holds for frail AF patients and the question whether these AFib patients on VKA should be switched to a NOAC remains heavily debated.”

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