This article is more than 5 years old. Information may no longer be current.
Experts compare novel oral anticoagulants with LAA closure in AF
SAN DIEGO — In the era of novel oral anticoagulants and the availability of devices for left atrial appendage closure, combining the two treatments may offer a better approach to reducing the risk for stroke in patients with atrial fibrillation.
During a debate at the Society for Cardiovascular Angiography and Interventions Scientific Sessions, two experts discussed the benefits and risks of using oral anticoagulants or LAA closure in detail.
LAA closure vs. novel oral anticoagulants
Matthew J. Price, MD, director of the cardiac catheterization laboratory at the Scripps Clinic, who argued in favor of more liberal use of LAA closure, highlighted current problems with oral anticoagulation.
“Despite all the talk, we don’t prescribe oral anticoagulants as much as we should,” Price said, noting that less than 50% of patients with nonvalvular AF who are indicated for oral anticoagulants actually receive them in the United States. “And novel oral anticoagulants, such as rivaroxaban (Xarelto, Janssen) and others, have not made much of a dent in that observation.”
Moreover, patients who are prescribed oral anticoagulants often do not take the medication for very long — an observation that has been made in randomized trials and registries, according to Price, a member of the Cardiology Today’s Intervention Editorial Board.
This is particularly true, he said, for warfarin, with data showing that only 30% to 50% of patients are still taking the medication after 2 or 3 years. Similarly, data from the GLORIA-AF registry showed that only 65% to 70% of patients on dabigatran (Pradaxa, Boehringer Ingelheim) were taking it at 3 years.
“I will also submit that the only benefit of novel oral anticoagulants is reducing intracranial hemorrhage and, in turn, mortality,” Price said.
In terms of other outcomes, novel oral anticoagulants are associated with similar or increased rates of gastrointestinal bleeding compared with warfarin. Additionally, only dabigatran, he noted, has demonstrated a signal for reducing the rates of ischemic stroke compared with warfarin.
On the other hand, Price said, the Watchman LAA Closure Implant (Boston Scientific) not only reduces intracranial hemorrhage and mortality but also reduces gastrointestinal bleeding.
According to data from the 5-year patient-level meta-analysis of the PROTECT-AF and PREVAIL trials, the device was associated with an 80% relative risk reduction in hemorrhagic stroke, a 41% relative risk reduction in CV death, a 27% reduction in all-cause death and significantly decreased major bleeding. These reductions in bleeding were mostly driven by a nearly 4% absolute risk reduction, or 80% relative risk reduction, in gastrointestinal bleeding with LAA closure. The device has also been shown to be particularly beneficial among younger patients, those with a lower risk for bleeding and women, Price noted.
Additionally, LAA closure is safe, as has been demonstrated in the NESTED post-approval study showing that the Watchman device exceeded the performance goal in terms of safety set by the FDA, Price said.
A compromise
During his response, C. Michael Gibson, MS, MD, professor of medicine at Harvard Medical School and chief of clinical research at Beth Israel Deaconess Medical Center, agreed that perhaps the biggest advantage of novel oral anticoagulants is the reduction in intracranial hemorrhage that subsequently drives a reduction in mortality.
However, he said, there exists a small reduction in ischemic stroke with the use of novel oral anticoagulants that is not currently statistically significant, but the data continue to accumulate. Gibson also acknowledged that the signal for a reduction in ischemic stroke occurs with the 150-mg dose of dabigatran and that an excess risk for bleeding does exist.
“The excess bleeding is very heterogeneous, though, and it depends on how bleeding was defined in these different trials,” he said. “It’s probably more homogeneous than it appears because some of the heterogeneity is based on variations in definitions.”
Nevertheless, novel oral anticoagulants are safer, according to Gibson. They can reduce the risk for bleeding by about 8% in the highest-risk patients, such as those who are on triple therapy. He also noted that data have linked these drugs with significant reductions in Bleeding Academic Research Consortium type 5b definite fatal bleeds. Furthermore, the substitution of a novel oral anticoagulant for warfarin in triple therapy is associated with an 8% reduction in the risk for CV hospitalization, he said.
Lower-dose novel oral anticoagulants may offer a solution, Gibson noted. Although not powered to evaluate efficacy, he said some data show that efficacy event rates with the lower-dose strategies are similar to those with higher-dose strategies. The lower, 2.5-mg dose of rivaroxaban, for instance, which is not yet available in the United States, has consistently shown promise and is being evaluated by the FDA.
The bottom line, Gibson said, is there are now safer alternatives to warfarin that can be used to treat these patients. Furthermore, he pointed out that the LAA closure devices do thrombose and are not entirely free of clots.
“I would propose a compromise rather than a winner-take-all approach,” he said. “We should consider a combination of very low-dose rivaroxaban with the Watchman device vs. a trial where the patient gets full-dose anticoagulation. The low, 2.5-mg dose might be just enough to prevent some of the device-associated thrombosis but not enough to cause meaningful bleeding.” – by Melissa Foster
References:
Gibson CM.
Price MJ. Preventing Cardioembolism: Left Atrial Appendage (LAA) Exclusion. Both presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; April 25-28, 2018; San Diego.
Disclosure: Price reports he has received grant or research support from Daiichi Sankyo and has received consultant fees or honoraria from Abbott Vascular, AstraZeneca, Boston Scientific, Chiesi USA, Medtronic and W.L. Gore and Associates. Gibson reports he has received research grant support and consultant fees from all major manufacturers of antiplatelets and antithrombins.