LAAC an Alternative for NOAC in Lower

NEW ORLEANS — In low-risk patients with atrial fibrillation for whom anticoagulation therapy would be indicated, device-based left atrial appendage closure (LAAC) was about equal to non-vitamin K antagonist oral anticoagulant (NOAC) therapy in preventing serious cardiovascular events. However, whether the procedure is an alternative for NOAC therapy to reduce stroke risk is an open question. LAAC “should be considered as an alternative to NOACs in a shared decision-making process with atrial fibrillation patients who are deemed suitable for long-term oral anticoagulation,” Saibal Kar, MD, an interventional cardiologist at Los Robles Medical Center in Thousand Oaks, California, said while presenting results from the CHAMPION-AF trial here at the annual meeting of the American College of Cardiology. The results were published simultaneously in The New England Journal of Medicine. The study evaluated the use of one LACC device, the Watchman FLX, and found it was noninferior for the composite endpoint of stroke, systemic embolism, and cardiovascular therapy, he said. The 3-year analysis of CHAMPION-AF included 1319 LAAC patients and 1305 on NOAC therapy. The LAAC group had 3 months of NOAC therapy with or without aspirin or dual antiplatelet therapy and continued on aspirin after the procedure. Kar said the two treatment groups were well matched, each with an average CHA2DS2-VASc scores of 3.5. Similar percentages of patients had CHA2DS2-VASc scores of 3 to 4 (58.4% NOAC, 57.6% LAAC) and 5 or greater (18.4% and 18.65). The average HAS-BLED score in both groups was 1.3. CHAMPION-AF Results The primary outcome, the rate of cardiovascular death, stroke, or systemic embolism, was 5.7% for LAAC patients and 4.8% for those on NOAC at 3 years, Kar said (P < .001). The less than 1% difference between the two was below the threshold for establishing noninferiority, he said. Kar acknowledged that the LAAC group had higher rates of ischemic stroke, 3.2% vs 2%, at 3 years, but on an annualized basis the difference is about.33%. The rate of nonprocedural bleeding was considered superior in the LAAC group, Kar said: 10.9% vs 19% for NOAC (P < .001). The rates for another key secondary safety endpoint, major bleeding as defined by the International Society on Thrombosis and Haemostasis, were close between the two treatment groups: 6.4% for NOAC and 5.9% for LAAC. The researchers also conducted an analysis of secondary net clinical benefit endpoint of cardiovascular death, stroke, systemic embolism, and nonprocedural bleeding and found that the difference between the two treatments was “highly statistically significant,” Kar said, with LAAC having a net rate of 15.1% vs 21.8% for NOAC (P < .001). In reply to a question from Medscape Medical News, Kar said the cost of the two approaches had not been studied, but that LAAC had cost certain advantages. "The cost of the procedure is up front,” Kar said. “What is not counted with the cost of anticoagulation drugs is the long-term need for blood thinners and all the hospitalization and comorbidities associated with bleeding.” Another drawback of anticoagulation therapy, he said, is that patients often have to pause the drugs when they have surgery, raising their risk for stroke in those untreated intervals. Kar acknowledged a number of limitations of the CHAMPION-AF findings, namely that the results may not apply to all LAAC devices and postimplant medication protocols. He also noted that the results may not apply to all AF patients, especially those with advanced heart failure and reduced ejection fraction, who were excluded from the study. Did CHAMPION-AF Patients Need Treatment? Jose Joglar, MD, an electrophysiologist at the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study, said the CHAMPION-AF results may have been so favorable for LAAC because many patients in the trial may not have needed either the procedure or anticoagulants. “We now know that modern study cohorts of atrial fibrillation patients are lower risk,” he told Medscape Medical News. “Because this trial did not include a control group, we cannot say for sure if the Watchman was so good because the stroke rate was really low, or would the stroke rate have been really low even if you had a control group?" Joglar said. He noted that the CHAMPION-AF results conflict with the recently published CLOSURE-AF results from Germany, which found that, overall, LAAC was worse than medical therapy for preventing stroke in high-risk patients. "In CLOSURE the patients did worse with the Watchman,” he said. “They tended to be older, they tended to be higher risk, but those are the patients you worry about.” Besides using lower-risk patients, recent AF studies are also easing the endpoints for noninferiority, Joglar said. "We do these studies having a lower-risk population and adding to the noninferiority endpoints additional things like mortality that are not expected to be different. What we're doing is making it easier to achieve noninferiority.” Meanwhile, patients want to know if they’ll have a lower risk for stroke with LAAC vs anticoagulation therapy. “But,” Joglar said, “the study is not powered for that." Pamela Mason, MD, director of the electrophysiology laboratory at the University of Virginia School of Medicine in Charlottesville, who was not involved in the study, said the size of the CHAMPION-AF study population was impressive, but that the findings themselves raise a number of questions. Citing the CLOSURE-AF results, she said, “Is there something about this device in particular that makes it a very safe device with low complication rates?" She wondered whether younger patients would be good candidates for Watchman because they have a longer-term possibility of benefit for bleeding risk. However, she also noted that anticoagulants are “ very safe and very effective” for stroke prevention. “When we think about procedures, we have to balance that acute procedural risk with long-term benefit." The CHAMPION-AF results at least raise the question of whether there is a “space” for discussing the preference for devices over anticoagulants for stroke prevention. “I don't think we can say that definitively." CHAMPION-AF was funded by Boston Scientific. Kar reports financial relationships with Abbott, Boston Scientific, Johnson & Johnson, Medtronic, InterShunt, Sierra Valve, HighLife Medical, inQB8 Med technologies, Edwards Lifesciences, CARDIOMECH, Occlutech, and W.L. Gore. Mason reports financial relationships with Boston Scientific and Medtronic. Joglar reports no relevant financial relationships. Richard Mark Kirkner is a medical journalist based in Philadelphia.