Left Atrial Appendage Closure vs. Novel Oral Anticoagulants with Watchman in Patients with Atrial Fibrillation

December 22, 2015
Andrew Smith

New analyses of Watchman trial data indicate that left atrial appendage closure might be a more cost-effective long-term treatment for atrial fibrillation than medication and that it may reduce the long-term risk of serious bleeds — but only at the price of more bleeds in the short term.

New analyses of Watchman trial data indicate that left atrial appendage closure (LAAC) might be a more cost-effective long-term treatment for atrial fibrillation (AF) than medication and that it may reduce the long-term risk of serious bleeds — but only at the price of more bleeds in the short term.

Investigators from Britain and the US constructed a Markov model to compare the 20-year cost effectiveness of appendage closure, warfarin and novel oral anticoagulants [NOACs] from the perspective of the Centers for Medicare & Medicaid Services. The model assumed that the average patient would be 70 years old at baseline and face a moderate risk of both stroke and bleeding.

The investigators used data from the PROTECT AF trial and meta-analyses of warfarin and NOAC performance to estimate relative outcomes and then estimated the long-term relative costs associated with both primary treatment and acute treatment of adverse outcomes.

The model predicted that appendage closure would become cost effective relative to warfarin by year 7 (at $42,994 per quality-adjusted life year [QALY]) and that it would become cost effective relative to NOACs by year 16 (at $48,446 per QALY). Moreover, after 10 years of treatment, appendage closure would provide the median patient more QALYs (5.855) than either warfarin (5.601) or NOACs (5.751).

Sensitivity analyses designed to see how different price assumptions would affect the study’s conclusion found that appendage closure would remain cost-effective relative to warfarin ($41,470 per QALY at 11 years) and NOACs ($21,964 per QALY at 10 years), even if procedure costs were doubled.

“Both NOACs and LAAC with the Watchman device were cost-effective relative to warfarin, but LAAC was also found to be cost-effective and to offer better value relative to NOACs,” the investigators wrote in the Journal of the American College of Cardiology. “The results of this analysis should be considered when formulating policy and practice guidelines for stroke prevention in AF.”

The other new analysis of Watchman performance looked at 2 randomized clinical trials and found that AF patients who underwent appendage closure were about as likely to experience a major bleed after a median of 3.1 years of follow-up as patients treated with warfarin (3.5 events vs. 3.6 events per 100 patient-years; rate ratio [RR]: 0.96; 95% confidence interval [CI]: 0.66-1.40; p = 0.84).

Surgery patients, however, were far more likely than warfarin patients to bleed in the first week of the study period (right after surgery) and far less likely to bleed in the period beginning 7 days after they were randomized (1.8 events vs. 3.6 events per 100 patient-years; RR: 0.49; 95% CI: 0.32-0.75; p = 0.001). The difference grew bigger still at the 6-month mark, when surgery patients stopped taking anticoagulation and antiplatelet medications (1.0 events vs. 3.5 events per 100 patient-years; RR: 0.28; 95% CI: 0.16 to 0.49; p < 0.001).

This pattern led the study investigators to predict that surgery would have been associated with a significantly lower risk of major bleeds than warfarin, if only the trials had followed up with patients over longer periods of time.

“There was no difference in the overall rate of major bleeding in patients assigned to LAA closure compared with extended warfarin therapy over 3 years of follow-up,” they wrote in Cardiovascular Interventions. “However, LAA closure significantly reduced bleeding beyond the procedural period, particularly once adjunctive pharmacotherapy was discontinued. The favorable effect of LAA closure on long-term bleeding should be considered when selecting a stroke prevention strategy for patients with nonvalvular AF.