PROTECT AF: 4-Year Results Show Superiority of Watchman Over Warfarin for A-fib

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For patients with nonvalvular atrial fibrillation (A-fib), closing the left atrial appendage (LAA) with the Watchman device is superior to warfarin alone with regard to avoiding stroke and mortality, according to 4-year results of the PROTECT AF trial presented May 9, 2013, at the Heart Rhythm Society 34th Annual Scientific Sessions in Denver, CO.

PROTECT AF, first published in August 2009 in the Lancet, randomized patients with nonvalvular A-fib to percutaneous LAA closure with the Watchman device (Boston Scientific, Natick, MA; n = 463) or ongoing warfarin treatment alone (n = 244) at 57 centers. The most recent data from the trial confirmed the noninferiority of the device for the primary composite efficacy endpoint (stroke, systemic embolism, and cardiovascular or unexplained death), although there was an increase in the primary composite safety outcome (procedure-related events and major bleeding).

At the meeting, Vivek Y. Reddy, MD, of the Mount Sinai School of Medicine (New York, NY), presented data for up to 60-month follow-up.

More than Noninferior

The primary efficacy event rate per 100 patient-years was lower with the Watchman device compared with controls (2.3% vs. 3.8%), demonstrating a 40% relative risk reduction (RR 0.60; 95% CI 0.41-1.05). Subgroup analysis maintained these results but showed slight differences based on gender, CHADS2 score, and A-fib pattern. Notably, efficacy was not diminished among patients with a history of TIA/stroke (table 1).

Table 1. Primary Efficacy: Relative Risk According to Subgroup

Per 100 Patient-Years


95% CI




CHADS2 Score
> 1



A-fib Pattern



History of TIA/Stroke



In addition, in an intention-to-treat analysis, patients who received the novel device were at reduced risk compared with warfarin-treated patients for both all-cause mortality (3.2% vs. 4.8%; HR 0.66; 95% CI 0.45-0.98; P = 0.0379) and cardiovascular mortality (1.0% vs. 2.4%; HR 0.40; 95% CI 0.23-0.82; P = 0.0045). Causes of death were balanced between the study arms, but those treated with warfarin were more likely to die from hemorrhagic stroke (2.9% vs. 0.4%; P = 0.0098).

The reduction in the primary efficacy outcome with Watchman was confirmed through a variety of analyses:

  • Intention-to-treat: HR 0.61; P = 0.0348
  • Post-procedure: HR 0.52; P = 0.0072
  • Per-protocol: HR 0.50; P = 0.0075
  • Terminal therapy: HR 0.52; P = 0.0166

Although warfarin had a clear advantage with regard to the primary safety endpoint early on, by 4 years the difference in the number of events had equalized between the groups (RR of 1.17 (95% CI 0.78-1.95) for Watchman vs. warfarin).

A Viable Alternative

“This is a significant development because for the first time we were able to demonstrate that the Watchman device was superior to warfarin for both primary efficacy and also mortality,” said Dr. Reddy in a prepared statement. “This has tremendous upside potential for patients.”

Because of increased risk of falls and bleeding in these patients, clinicians “often feel uncomfortable with lifelong systemic anticoagulation therapy,” he continued. These data “provide additional support for LAA closure as a potential viable long-term alternative to chronic warfarin therapy for patients to reduce the risk of stroke.”

‘Proof of Concept’ In, But Questions Remain

Although previous studies have only shown noninferiority of Watchman compared with warfarin, Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview that “we thought it was likely that eventually we would reach superiority, and this really [nailed it down].”

“We have proven that the left atrial appendage is a critical component of stroke in patients with atrial fibrillation and that eliminating the appendage has a profound impact on the long-term outcome such that the risk of ischemic stroke over this 4-year period now is the same as on warfarin and the risk of hemorrhagic stroke is dramatically reduced,” Dr. Sommer said.

Still, many questions remain, he noted, adding, “This is just one of many new therapies that are available—we really have no comparison so far to any of the novel anticoagulants [or to] the other left atrial appendage closure devices,” he said.

Looking at the subgroup data, Dr. Sommer highlighted the differences in event rate based on gender, CHADS2 score, and A-fib pattern. “[These data] are hinting at [patterns], but we don’t really know what any of it means. . . . Data like these [will] accumulate, [and] are going to help steer us toward trying to figure out which patient will do best with which therapy,” he explained.

“The proof of concept is in,” Dr. Sommer concluded. “Now we just have to figure out which of the devices is going to be the best and how we stratify patients for this type of strategy.”


Reddy VY. Long term results of PROTECT AF: The mortality effects of left atrial appendage closure versus warfarin for stroke prophylaxis in AF. Presented at: Heart Rhythm Society 34th Annual Scientific Sessions; May 9, 2013; Denver, CO.



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  • Dr. Reddy reports receiving grant support from and consulting for Boston Scientific, Coherex Medical, and St. Jude Medical.
  • Dr. Sommer reports serving as a PI for both the PREVAIL trial and the CAP2 registry.