DOACs for stroke prevention safe in most high-risk populations with AF
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Key takeaways:
- Many high-risk groups of patients with atrial fibrillation can use direct oral anticoagulants safely.
- Patients with AF and rheumatic heart disease should be on a vitamin K antagonist instead of a DOAC.
PHILADELPHIA — Direct oral anticoagulants for stroke prevention in patients with atrial fibrillation are safe in most high-risk populations, a speaker said during the Heart in Diabetes CME Conference.
Meta-analyses have shown that direct oral anticoagulants (DOACs) are better than vitamin K antagonists such as warfarin for prevention of stroke and systemic embolism, and trend toward being better than vitamin K antagonists at avoiding major bleeding, particularly intracranial hemorrhage, P. Gabriel Steg, MD, chief of the cardiology department at Hôpital Bichat, Paris, and professor of cardiology at the Université de Paris, said during a presentation.
However, he said, “there are a number of new findings in this space, and a lot of new evidence that is being accumulated in high-risk subgroups.”
For example, “the temptation would be to withhold anticoagulation in the very elderly patient for fear of bleeding, but when you look at the data, [they have] consistently shown that there is no interaction with age in terms of either benefit or safety of anticoagulation,” Steg said. “My overall take would be that while this remains an individualized decision to make with the patient and his or her family, overall, there is no strong argument that we should withhold anticoagulation solely on the basis of age, including when we are using direct oral anticoagulants.”
Nor is there any association between risk for fall and risk for bleeding, so the risk for fall-induced bleeding does not outweigh the benefits of stroke prevention in older patients, he said.
Among those with AF requiring stroke prevention, patients with chronic kidney disease have worse outcomes than patients without CKD, but “what’s interesting is that the benefit of direct oral anticoagulants over warfarin actually increases as kidney function worsens,” Steg said, noting that the practice of preferring warfarin to DOACs because of concern about bleeding risk in patients with AF and chronic kidney disease is not supported by data.
In addition, low-dose DOACs are not better than standard-dose DOACs in this population because they are linked to higher rates of death and thromboembolism, he said.
For patients with AF on dialysis, the DOAC apixaban (Eliquis, Bristol Myers Squibb/Pfizer) was approved for stroke prevention based on observational data, but randomized trials of DOACs in this population are starting to be conducted, Steg said.
Much work has been done on determining optimal regimens for patients with AF who have CAD and have undergone PCI, and data show that for patients who get triple therapy (an oral anticoagulant for the AF plus dual antiplatelet therapy after stenting), “the risk of bleeding can be unbearable,” Steg said during the presentation.
Trials have consistently found that “when you use [DOAC]-based dual antithrombotic therapy, ie, dropping aspirin quickly after PCI and keeping a [DOAC] plus a P2Y12 inhibitor, you reduce bleeding; you do not affect death, MACE, stroke or MI; and there are maybe some question marks about a potential increase in the risk of stent thrombosis, but that is not statistically significant,” he said. “That has been confirmed in subsequent meta-analyses.”
The data are less clear for patients with AF and stable CAD, as the two randomized trials comparing oral anticoagulation alone with oral anticoagulation plus single antiplatelet therapy in that population contradicted each other, Steg said, noting the ongoing AQUATIC trial could be the tiebreaker.
For patients with AF who have had a recent stroke, what to do with anticoagulation depends on the type of stroke, he said. For patients who had a hemorrhagic stroke, most should not resume anticoagulation and receive left atrial appendage occlusion instead, but for patients who had an ischemic stroke, “we don’t really know what to do,” he said.
Though European guidelines suggest resuming anticoagulation 1 day after a transient ischemic attack, 3 days after a mild stroke, 6 days after a moderate stroke and 12 days after a severe stroke, “it’s totally based on opinion rather than any evidence,” Steg said. He said the first randomized trial on this issue, the ELAN trial published in May, early anticoagulation (within 48 hours after a minor stroke and 6 to 7 days after a major stroke) and late anticoagulation (3 or 4 days after a minor stroke and 12 to 14 days after a major stroke) had no difference in bleeding, but efficacy trended in favor of early anticoagulation.
DOACs were assumed to be unfit for patients with AF and a bioprosthetic heart valve, but the RIVER trial showed low-dose rivaroxaban (Xarelto, Janssen/Bayer) was noninferior to warfarin in that population, Steg said.
In patients with rheumatic heart disease and AF, vitamin K antagonists remain the standard of care, as the INVICTUS trial showed that rivaroxaban was inferior to vitamin K antagonists, Steg said.
“I don’t think that’s good news, because even though rivaroxaban is more expensive than vitamin K antagonists, it would allow more patients to be treated because it does not need monitoring,” Steg said.
References:
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Steg PG. Session 17 – Stroke in Cardiometabolic Conditions and Diabetes. Presented at: Heart in Diabetes CME Conference; June 9-11, 2023; Philadelphia.
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