Switching from VKA to DOAC Increases Bleeding Risk in Elderly frail patients

The risk of bleeding increased by about 60% in the oldest and frailest patients who were shifted from a VKA compared to those who stayed on the conventional medication.

A new study presented at the European Society of Cardiology (ESC) 2023 Congress in Amsterdam found that the elderly and frail who switched from a vitamin K antagonist (VKA) to a direct oral anticoagulant (DOAC) to treat atrial fibrillation had a 69% higher risk of bleeding.

The findings were unexpected to the researchers who conducted the study.

According to data from the FRAIL-AF research, making this move was not only linked to an increased risk of bleeding compared to continuing VKA medication for these patients, but it also had no effect on stroke prevention.

These results were surprising, the researchers said at a press conference before the presentation, since prior studies had shown that DOAC blood thinners were safer than VKAs for non-frail individuals with atrial fibrillation. Frail elderly individuals with atrial fibrillation should not be switched from VKA blood thinners to DOAC blood thinners "without a clear indication."

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Frail elderly individuals with atrial fibrillation should not be switched from VKA blood thinners to DOAC blood thinners "without a clear indication."_______________________________________

If a patient is just beginning to take anticoagulants, current recommendations recommend that they begin with a DOAC. Since the first DOACs were authorised a decade ago, many elderly patients have been shifted from VKAs to DOACs despite scant evidence. A news statement from the European Society of Clinical Oncology (ESC) states that the organisation now recommends transitioning to a DOAC "especially if the time in therapeutic range is not well-controlled despite good drug adherence."

Researchers from the University Medical Centre in Utrecht, the Netherlands, set out to answer this issue due to a dearth of information comparing VKAs and DOACs in the most vulnerable elderly patients and, more especially, due to a lack of evidence surrounding switching. Between January 2018 and April 2022, they randomly assigned 1330 patients 1:1 to continue taking a VKA or switch to a DOAC using funding from the Dutch government and unrestricted educational grants from pharmaceutical firms making DOACs.

Principal investigator Geert Jan Geersing, MD, PhD, of UMC Utrecht, who presented the data during a press event, said that the researchers could make no conclusions regarding the relative safety of various DOACs employed in the trial due to the fact that clinicians were able to pick the DOAC of their choosing.

The average age of the participants was 83, and around 38% of them were female. In order to take part, patients needed to be at least 75 years old and have a Groningen Frailty Indicator score of 3. One of seven thrombosis centres in the Netherlands was using VKAs to treat all patients.

The results were presented in a hotline session on Sunday by Dr. Linda Joosten of the Julius Centre for Health Sciences and Primary Care in Utrecht, the Netherlands.

Results. The experiment was stopped for futility after 163 primary outcome events, 101 of which occurred in the group that switched to DOACs and 62 in the group that remained on VKAs, as predicted by the Data Safety and Monitoring Board. The following were the outcomes:

Switching from a VKA to a DOAC was associated with a lower risk of major or clinically significant non-major bleeding (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.23 to 2.32; P =.001).

• Thromboembolic events as a secondary outcome: HR, 1.26 (95% CI, 0.60 to 2.61).

All-cause mortality was a secondary outcome with a 95% confidence interval (CI) of 0.96 to 1.45.

Patients with atrial fibrillation have had greater clinical benefit from DOAC use since its introduction, perhaps because to reduced bleeding complications. The primary investigator told reporters that the lack of monitoring with DOACs might have contributed to the unexpected result, but that VKAs do need such monitoring.

Geersing said, "We're not just comparing molecules; we're also comparing strategies."

Geersing said that the elderly, who often need the help of others and suffer from a variety of chronic diseases and drugs, are among the most at-risk patients. One in four or five people have atrial fibrillation, and the risk of stroke is rather substantial, he added.

The findings will be published in the American Heart Association's flagship journal, Circulation.

Reference

Study reports on switch to newer anticoagulants in frail elderly with atrial fibrillation. European Society of Cardiology. News release. August 27, 2023. Accessed August 28, 2023. https://www.escardio.org/The-ESC/Press-Office/Press-releases/Study-reports-on-switch-to-newer-anticoagulants-in-frail-elderly-with-atrial-fibrillation