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Frail Elderly at High Risk of Bleeding Following VKA-DOAC Switch: Surprise Outcome Shared at ESC Congress
Oldest and most frail elderly were at more than 60% greater risk of bleeding when switched from a VKA than those who remained on the traditional agent.
A 69% higher risk of bleeding was reported among the oldest, most frail patients switched from a vitamin K antagonist (VKA) to a direct oral anticoagulant (DOAC) to treat atrial fibrillation, according to finding of a new study reported on Sunday at the European Society of Cardiology (ESC) 2023 Congress in Amsterdam.
The results came as a surprise to the study authors.
Results from the FRAIL-AF study found that making such a switch was not only associated with more bleeding compared with keeping these patients on VKA therapy—the switching also did not help prevent strokes.
“These were unexpected findings, given that previous trials in non-frail patients with atrial fibrillation showed that DOAC blood thinners were safer compared to VKAs,” the investigators stated in conclusions during a press briefing ahead of the presentation. “Without a clear indication, switching from VKA blood thinners to DOAC blood thinners should not be considered in frail elderly patients with atrial fibrillation.”
“Without a clear indication, switching from VKA blood thinners to DOAC blood thinners should not be considered in frail elderly patients with atrial fibrillation.”
Current guidelines call for starting patients on DOACs if taking anticoagulants for the first time. Despite limited data, many elderly patients have been switched from VKAs to DOACs since the first DOACs were approved a dozen years ago. According to a press release from ESC, the organization’s current guidelines recommend considering switching to a DOAC, “especially if the time in therapeutic range is not well-controlled despite good drug adherence.”
The lack of data comparing VKAs and DOACs in the frailest elderly patients, and, specifically, the lack of evidence surrounding switching prompted the investigators from the University Medical Center in Utrecht, the Netherlands, to examine this question. With financial support from the Dutch government and unrestricted educational grants from pharmaceutical companies that make DOACs, they randomized 1330 patients 1:1 between January 2018 and April 2022 to either stay on a VKA or switch to a DOAC.
Clinicians were allowed to select the DOAC of their choice, and principal investigator Geert Jan Geersing, MD, PhD, of UMC Utrecht, who presented the results during a press briefing, said the team could draw no conclusions about relative safety of different DOACs used in the study.
The mean age of participants was 83, and 38.8% were women. Patients had to be at least 75 years of age and have a Groningen Frailty Indicator score of 3 or higher to participate. All patients were being managed with VKAs at 1 of 7 participating thrombosis centers in the Netherlands.
Linda Joosten, MD, of the Julius Center for Health Sciences and Primary Care in Utrecht, the Netherlands, presented the findings in a hotline session Sunday.
Results. After 163 primary outcome events—101 among those that switched to DOACs and 62 among those that stayed on VKAs—the trial was halted for futility following advice from the Data Safety and Monitoring Board, per a prespecified futility analysis. Results were as follows:
- For the primary outcome of major or clinically relevant non-major bleeding: HR, 1.69 (95% CI, 1.23 to 2.32), P = .001, for switching to a DOAC relative to a VKA.
- For the secondary outcome of thromboembolic events: HR, 1.26 (95% CI, 0.60 to 2.61).
- For the secondary outcome of all-cause mortality: HR, 0.96 (95% CI, 0.64 to 1.45).
Use of DOACs since their arrival has been associated with better clinical benefit for patients with atrial fibrillation, due to lower rates of bleeding. DOACs also do not require the monitoring associated with VKAs, although the principal investigator told reporters that that the absence of monitoring with DOACs could have contributed to the unexpected outcome.
“We are not comparing just molecules but also strategies,” said Geersing,
The frail elderly are especially vulnerable patients, Geersing said, as they have multiple chronic conditions, take many medications, and typically rely on others for assistance. Atrial fibrillation is common in this group; the condition affects 1 in every 4-5 persons, and stroke risk is high, he said.
Results will be published in the journal Circulation, the official publication of the American Heart Association.
