PROTECT AF Data Published for Boston Scientific's Watchman LAA Closure Device

November 19, 2014—Follow-up data at approximately 4 years from the PROTECT AF trial were published by Vivek Y. Reddy, MD, et al in JAMA: Journal of the American Heart Association (2014;312:1988–1998).  

PROTECT AF was conducted to determine whether a local strategy of mechanical left atrial appendage (LAA) closure—using the percutaneous transcatheter Watchman LAA closure device (Boston Scientific Corporation)—was noninferior to warfarin. The Watchman LAA closure device is indicated to prevent thromboembolism from the LAA. 

As reported on October 8, 2014, the Circulatory System Devices Panel of the US Food and Drug Administration met in Gaithersburg, Maryland, to consider updated information, including PROTECT AF data, to determine if the device should be recommended for approval in the United States. The Watchman device was approved for sale in Europe in 2005.

The background of the PROTECT AF study is that although warfarin is known to be effective in preventing stroke in patients with atrial fibrillation (AF), the drug is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions.

As summarized in JAMA, PROTECT AF was a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals and composed of 707 patients with nonvalvular AF and at least one additional stroke risk factor (CHADS2 score ≥ 1). Patients were enrolled between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability > 97.5% and superiority a probability of 95% or greater. The noninferiority margin was a rate ratio of 2, comparing event rates between treatment groups.

In the study, patients were randomized to LAA closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2–3). A composite efficacy endpoint including stroke, systemic embolism, and cardiovascular/unexplained death was analyzed by intention to treat.

The investigators reported that at a mean (standard deviation) follow-up of 3.8 (1.7) years (2,621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years compared to the warfarin group with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years (rate ratio, 0.6; 95% credible interval, 0.41–1.05), meeting prespecified criteria for both noninferiority (posterior probability > 99.9%) and superiority (posterior probability 96%). 

Patients in the device group demonstrated lower rates of both cardiovascular mortality (1 event per 100 patient-years for the device group [17/463 patients; 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients; 9%]; hazard ratio, 0.4; 95% confidence interval, 0.21–0.75; P = .005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients; 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients; 18%]; hazard ratio, 0.66; 95% confidence interval, 0.45–0.98; P = .04).

After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority compared with warfarin for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality, concluded the PROTECT AF investigators.