In frail patients with AF, switching to newer anticoagulants raises bleeding risk
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Key takeaways:
- Newer oral anticoagulants increased bleeding risk in frail patients with AF when switched from a vitamin K antagonist.
- The newer anticoagulants did not reduce stroke risk or improve mortality rates.
Switching older patients with frailty syndrome and atrial fibrillation to a non-vitamin K antagonist from their old blood thinner caused significant bleeding risk and no greater protection from stroke, a speaker reported.
These “unexpected findings” indicate that without a clear indication, older patients with frailty syndrome and AF may benefit from remaining on their vitamin K antagonist rather than being switched to a non-vitamin K antagonist oral anticoagulant (NOAC), according to a presentation at the European Society of Cardiology Congress.
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“I want to stress that it was a unique population that we included in our study that was not yet included in previous trials, namely, frail elderly patients,” Geert-Jan Geersing, MD, PhD, associate professor at Julius Center UMC Utrecht, Utrecht University, the Netherlands, said during a press conference. “It’s important to consider the complexity of the frailty syndrome. It is not about just having a high age or having multiple diseases or a lot of medications. It’s all these things together with a high dependency on others and reduced capacity to resist stressors.
“About 10% of the population lives with frailty syndrome, and from a cardiology perspective, it’s important to consider that atrial fibrillation is actually really common in these patients. Some say one in four, but there are other studies that say it’s even higher,” he said. “What’s even more important is that because of this atrial fibrillation, if they’re not treated with blood thinners, there’s a high risk for stroke. It could reach about 10%. So without any doubt, these patients need to be treated with blood thinners.”
Geersing said vitamin K antagonists — for which 11 million prescriptions have been given in 2020 — have been a mainstay anticoagulant for more than 50 years. While unlike vitamin K antagonists, newer NOACs, including apixaban (Eliquis, Bristol Myers Squibb/Pfizer), dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Janssen/Bayer) and edoxaban (Savaysa, Daiichi Sankyo), do not require weekly blood tests, but there is a paucity of data on their use in a population with frailty syndrome, according to the presentation.
Geersing and colleagues conducted the pragmatic, open-label, investigator-initiated FRAIL-AF trial to better understand the effects of NOACs among patients with frailty syndrome and AF.
The study cohort included 661 patients taking a vitamin K antagonist (mean age, 83 years; 36% women) and 662 who were switched from a vitamin K antagonist to a NOAC (mean age, 83 years; 41% women).
The primary outcome was a composite of major and clinically relevant non-major bleeding during 1-year follow-up. Secondary outcomes include thromboembolic events and all-cause mortality.
In the cohort, 35.8% to 39.8% of patients had memory complaints at baseline and nearly 17% were unable to walk through their homes without help.
At 1 year, Geersing reported a 69% increased risk for bleeding among patients with frailty syndrome who switched to a NOAC compared with those who remained on their vitamin K antagonist (HR = 1.69; 95% CI, 1.23-2.32; P = .00112).
The researchers observed an increased risk for both major bleeding (HR = 1.52; 95% CI, 0.81-2.87) and clinically relevant nonmajor bleeding, individually (HR = 1.77; 95% CI, 1.24-2.52), as well as elevated but not statistically significant thromboembolic risk (HR = 1.26; 95% CI, 0.6-2.61) among patients who switched to a NOAC.
Moreover, 1-year all-cause mortality was similar between the two groups (HR = 0.96; 95% CI, 0.64-1.45).
“We show that in older, frail patients with atrial fibrillation who use blood thinners for stroke prevention, the risk of bleeding is 69% higher if they are switched to a newer blood thinner compared to if they continue using their traditional [vitamin K antagonist] blood thinner,” Geersing said during the press conference. “NOAC blood thinners were not more effective in terms of stroke reduction. I would like to stress here, these were unexpected findings given that previous trials, in fact, showed that in non-frail older patients with atrial fibrillation, NOAC blood thinners are actually safer compared to [vitamin K antagonists].
“Without a clear indication, switching from a [vitamin K antagonist] blood thinner to a NOAC blood thinner should not be considered in frail, elderly patients with atrial fibrillation because of a 69% increase of bleeding complications,” he said.
Reference:
Perspective
Back to TopThe most important take-home message is that switching to NOAC was associated with more bleeding yet no reduction in stroke in frail patients with AF.
The results were very surprising, since historically NOACs have been shown to be safer in the general population. This is especially true for intracerebral bleeding, which is lower in NOACs, and the elderly are at risk for it.
For sure, there is no reason to switch patients who are stable on vitamin K antagonists with stable International Normalized Ratios. We are now questioning the wisdom of NOACs safety in the frail patients.
One study, ELDERCARE AF, showed that very low-dose edoxaban is a possible option. Perhaps we need to look at studies on frail patients and start from scratch since they are clearly not the same risk as the general population. Perhaps lower NOAC dosing would be better in this group.
Perspective
Back to Top
Luigi Di Biase, MD, PhD, FACC, FHRS
FRAIL-AF is a very important trial. NOACs may increase the bleeding risk in frail patients, but I'm not convinced vitamin K antagonists are the way to go because compliance with them is hard. It's difficult for the patient to be in a therapeutic range above 2 and below 3 to 3.5. Therefore, although this study might be in favor of vitamin K antagonists, a randomized trial in this frail population should be done. With current availability of left atrial appendage closure devices, meaning the patient could completely stop any type of anticoagulation and be on aspirin for life, the right trial should include a closure device for the frail population. Left atrial appendage closure should be the way to go in these patients pending an appropriate randomized controlled trial.
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Geersing GJ, et al. Hot line 6. Presented at: European Society of Cardiology Congress; Aug. 25-28, 2023; Amsterdam (hybrid meeting).
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