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In patients with atrial fibrillation (A-fib), the Watchman left atrial appendage closure device can be safely implanted without a period of concurrent warfarin anticoagulation, achieving stroke protection similar to that of patients who receive transitional warfarin. The finding appears to open the door to offering mechanical stroke prophylaxis to a large subset of A-fib patients who cannot tolerate warfarin and who were excluded from an earlier randomized trial of the device.

The registry data were presented May 11, 2012, at the Heart Rhythm Society 33rd Annual Scientific Sessions in Boston, MA. The Watchman (Atritech/Boston Scientific, Plymouth, MN) is currently an investigational device in the United States but is approved in Europe.

In the PROTECT AF trial, published in the Lancet in 2009, researchers randomized patients with nonvalvular A-fib who were receiving warfarin to the Watchman with conditional discontinuation of the drug or to continuation on warfarin alone. Watchman-treated patients who stopped warfarin were then prescribed clopidogrel until 6-month follow-up and aspirin indefinitely. The Watchman proved noninferior to warfarin with regard to efficacy, although safety events were more common in the intervention group due primarily to periprocedural complications.

The trial protocol required that patients remain on warfarin for at least 45 days following implantation. Termination of the drug was conditioned on transesophageal echocardiographic evidence of either complete closure of the left atrial appendage or minimal residual flow around the device.

Going Warfarin-Free

For the current ASAP (ASA Plavix Registry) study, Vivek Y. Reddy, MD, of the Mount Sinai School of Medicine (New York, NY), and colleagues prospectively evaluated outcomes for 150 nonvalvular A-fib patients with a contraindication to warfarin who were implanted with the Watchman at 4 European centers. Post implantation, they were prescribed clopidogrel (75 mg daily) for 6 months and lifelong aspirin (81-325 mg daily).

After a mean follow-up of 14.4 ± 8.6 months, the rate of ischemic stroke was 1.7% per 100 patient-years, a 77% reduction relative to the 7.3% rate predicted for historic controls with the same CHADS2 score on aspirin alone, and a 67% reduction from the 5.1% rate for similar patients on aspirin and clopidogrel. The ischemic stroke rate was similar to the 2.2% incidence observed in PROTECT AF.

In addition, there were 9 deaths (5%) and 1 hemorrhagic stroke (0.6%). Safety events included pericardial effusion with tamponade in 3 patients, device embolization in 2 patients, device thrombus in 6 patients (1 with stroke), and major bleeding in 4 patients.

“These results are very impressive and show potential for an effective device-based solution for higher-risk patients with limited pharmacologic options to reduce their risk of stroke,” Dr. Reddy said in a prepared statement.

In a telephone interview with TCTMD, Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), estimated that of the significant number of A-fib patients with contraindications to warfarin, the percentage with an absolute contraindication is relatively small. “Most of the time, contraindications are relative,” he said, citing 2 groups: people who are fairly young and unwilling to restrict sports, for example, and elderly patients at high risk of hemorrhagic complications.

In the PROTECT AF trial and the ongoing PREVAIL study (designed to support US Food and Drug Administration approval of the Watchman), Dr. Sommer noted, all patients had to be warfarin-eligible in order to be randomized to the Watchman or the standard anticoagulant.

Post-Implantation Embolization Risk Low

But beyond that, he explained, warfarin was continued for a time in Watchman patients to allow the device to become endothelialized. “Once the appendage is mostly closed, the chances of a thrombus forming in there and getting out if there’s a tiny residual leak are dramatically reduced,” he said, adding, “This is an important step toward learning the natural history of how the body adapts to the device.”

In fact, a subsequent PROTECT AF analysis (Viles-Gonzalez JF, et al. J Am Coll Cardiol. 2012;59;923-929) showed that minimal residual flow had little impact on clinical embolic events.

“I think analogies can be drawn to the [patent foramen ovale (PFO)] experience,” Dr. Sommer said. “Even though we don’t get immediate complete closure with most PFOs, the chances of a clot finding its way through one of these little cracks are very small.”

He added that aspirin and clopidogrel are typically prescribed after atrial septal defect [ASD] and PFO closure to minimize the risk of thrombus formation on the patch.  “Whether it’s an ASD device or a left atrial appendage device sticking into the left atrium, it probably doesn’t make that much difference,” Dr. Sommer said. “We never put ASD and PFO patients on warfarin, so it’s really no surprise that patients did as well on antiplatelet therapy after closure of the left atrial appendage as they did on 45 days of warfarin.”

Dr. Sommer said he was confident that data from the PROTECT AF and PREVAIL trials will lead to FDA approval. “Then physicians will be able to manage [Watchman] patients post implantation however they want,” he commented.

Study Details

Patients’ average age was 72.5 ± 7.4 years, and the mean CHADS2 score was 2.8 ± 1.2. Implantation was successful in 94.7% of patients. 

Contraindications to warfarin included a history of overt bleeding (67.3%), hemorrhagic tendencies (26.0%), or blood dyscrasias (7.3%), and unsupervised senility (4.0%). Most of the remaining patients had skin or liver issues with the drug. 

 

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Source:
Reddy VY. First formal analysis of the “ASA Plavix Registry” (ASAP): Watchman left atrial appendage closure in atrial fibrillation patients with contraindication to oral anticoagulation. Presented at: Heart Rhythm Society 33rd Annual Scientific Sessions; May 11, 2012; Boston, MA.

 

 

Related Stories:

• PROTECT AF Published: Percutaneous Device Eliminates Need for Warfarin in Many AF Patients
• Watchman Gains Momentum for Treatment of AF
• Lack of Complete Seal with Watchman Device Common, But No Cause for Alarm

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