Watchman Device for LAA Closure Provides Net Clinical Benefit vs. Warfarin in A-fib Patients

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In patients with atrial fibrillation (A-fib), percutaneous closure of the left atrial appendage (LAA) confers a net clinical benefit compared with warfarin anticoagulation, according to a study of the combined impact of the complications and treatment effects of the 2 therapies. Moreover, post-hoc analysis of the PROTECT-AF trial and its continued access registry, published online September 24, 2012, ahead of print in the European Heart Journal, suggests the advantage of LAA closure becomes more pronounced as complication rates decline with growing operator experience. 

The original trial, published in August 2009 in the Lancet, randomized patients with nonvalvular A-fib in a 2:1 ratio to percutaneous LAA closure with the Watchman device (Atritech, Plymouth, MN; n = 463) or ongoing warfarin treatment alone (n = 244). Although the device was found to be noninferior to warfarin for preventing stroke, systemic embolism, and cardiovascular death, it was associated with a significantly higher risk of complications, in particular pericardial effusion and procedural stroke. Although still investigational in the United States, the Watchman device has gained regulatory approval in Europe and parts of Asia. 

To determine the net clinical effect of LAA closure, investigators led by Vivek Y. Reddy, MD, of Mount Sinai School of Medicine (New York, NY), examined outcomes in patients enrolled in the randomized trial and those from the Continued Access PROTECT-AF (CAP) registry (n = 566).

Event Types, Risk Factors Assessed

Based on follow-up of 1,623 person-years (mean 28 ± 13 months per patient) in PROTECT-AF and 741 person-years (mean 16 ± 7 months per patient) in the CAP registry, the investigators calculated the annualized rates of the key outcomes, with the incidence of thromboembolic events, intracranial hemorrhage, and notably pericardial effusion requiring intervention declining in the registry group compared with the trial closure arm (table 1).

Table 1. Annualized Event Rates: Closure vs. Warfarin in PROTECT-AF, CAP Registry

Event Type

LAA Closure in Trial
(n = 463) 
(95% CI)

LAA Closure in Registry
 (n = 566)
(95% CI)

Warfarin in Trial
(n = 244)
(95% CI)


1.80%  (1.68-1.94)

1.35% (1.26-1.45)


Intracranial Hemorrhage

0.19% (0.15-0.23)

0.13% (0.11-0.17)


Pericardial Effusion Requiring Intervention

1.81% (1.69-1.94)

1.08% (0.99-1.17)


Major Bleeding Requiring Transfusion

1.24% (1.14-1.34)

3.24% (3.09-3.39)


All-Cause Death

3.24% (3.08-3.41)

4.04% (3.89-4.22)

4.54 (4.27-4.81)

In the trial, the net clinical benefit favored LAA closure (1.74%/year), although the authors note that the confidence interval crossed zero (95% CI – 0.54 to 4.39), which is consistent with no benefit or possible harm. On the other hand, in the registry, with experienced trial operators performing closure procedures, the net clinical benefit increased to 4.97%/year with an acceptable confidence interval (95% CI 3.07-7.15).

Net clinical benefit was greatest in trial patients with a history of stroke, and higher CHADS2 scores. Net benefit also was greater in older and diabetic patients and those at higher bleeding risk. The same pattern held true for registry patients, with increases in benefit that were proportionally larger (table 2).

Table  2. Annual Net Clinical Benefit of LAA Closure in PROTECT-AF, CAP Registry

Risk Factor

(n = 707)
(95% CI)

(n = 810)
(95% CI)

Prior Stroke or TIA

4.30% (-2.07 to 11.25)

8.68% (2.82-14.92)

CHADS2 score of 2

1.37% (- 2.14 to 6.02)

4.89% (1.75-8.82)

Age ≥ 75 years

1.18% (-3.16 to 5.89)

6.92% (3.50-10.84)


2.19 (-2.57 to 8.04)

6.84 (2.98-11.52)

ATRIA Bleeding Score ≥ 4

2.78 (-2.85 to 9.06)

7.98 (3.91-12.93

Identifying Patients Who Benefit Most from Closure

In a telephone interview with TCTMD, Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), pointed to what he called the “main downsides” of the study it is a post-hoc analysis with a questionable weighting scheme used to assign relative values to adverse events. For example, he noted, an ischemic stroke was considered one-third as bad as an intracranial hemorrhage, and an ischemic stroke was deemed only twice as bad as having a pericardial effusion. “That doesn’t seem right,” he commented. “Obviously, there are ‘fudge’ factors in any post-hoc-type analysis.”

On the plus side, Dr. Sommer said the finding of greater net benefit of closure with higher CHADS2 scores, though not surprising, is important “because [LAA closure] may be a good adjunct procedure for patients who have a high CHADS2 score and continue to be at risk even on anticoagulation. The 2 [therapies] may go hand-in-hand when you’re trying to protect these patients.”

Moreover, Dr. Sommer said, “these types of scales where we can give points for [risk factors] can be very useful clinical tools if they are validated prospectively.

“I think the Watchman device will get approved the next time the FDA reviews it,” Dr. Sommer predicted. “And once it’s available, patients will have to decide [between anticoagulation and LAA closure]. If we have a way to choose between patients that, based on x, y, and z, are most likely to benefit from LAA closure, and those for whom it probably doesn’t matter, that’s going to be incredibly helpful.”

The field of A-fib management is evolving very rapidly, Dr. Sommer added, especially with the growing repertoire of new oral anticoagulants. For example, he noted, “the [expected] approval of apixaban is going to have a significant impact because it seems to be much safer than either rivaroxaban or dabigatran. It may actually be a wonder drug for patients for whom the difference between LAA closure and anticoagulation is not so great. [On the other hand,] if we can pick out the patients [for whom] the difference is much larger, I think those are the ones who will get the procedure.”

“The overall value of a paper like this is that it tries to come up with a lucid strategy for choosing which patients should get which therapy,” Dr. Sommer concluded. 

“It’s encouraging that there is a net clinical benefit derived from LAA closure,” Steven Y. Yakubov, MD, of Riverside Methodist Hospital (Columbus, OH), told TCTMD in a telephone interview. “And it looks like procedural complications are decreasing, which allows that benefit to appear earlier. We’re seeing the effect of the learning curve.”

 Dr. Yakubov also noted that since many clinicians now believe warfarin is no longer the best anticoagulant strategy for A-fib and are switching to the newer agents, it may not be the ideal trial comparator for LAA closure.


Gangireddy SR, Halperin JL, Fuster V, et al. Percutaneous left atrial appendage closure for stroke prevention in patients with atrial fibrillation: An assessment of net clinical benefit. Eur Heart J. 2012;Epub ahead of print.



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Watchman Device for LAA Closure Provides Net Clinical Benefit vs. Warfarin in A-fib Patients

In patients with atrial fibrillation (A-fib), percutaneous closure of the left atrial appendage (LAA) confers a net clinical benefit compared with warfarin anticoagulation, according to a study of the combined impact of the complications and treatment effects
  • Dr. Reddy reports receiving consulting fees from Atritech and Boston Scientific.
  • Dr. Sommer reports serving as a principal investigator for the PREVAIL trial.
  • Dr. Yakubov reports serving as a speaker for Boeringer Ingelheim.