Does the Watchman LAA Occluder Reduce Bleeding?

Beyond the periprocedural period, use of the Watchman device for left atrial appendage (LAA) closure reduces the risk of major bleeding compared with chronic warfarin therapy, according to an analysis of data from 2 pivotal RCTs. However, an accompanying editorial questions the exclusion of periprocedural events from the analysis, suggesting it “should be viewed as biased” toward the device.

The study was published online November 25, 2015 ahead of print in JACC: Cardiovascular Interventions.

Investigators led by Matthew J. Price, MD, of Scripps Clinic (La Jolla, CA), carried out a pooled, patient-level analysis of major bleeding events in 1,114 patients (mean age, 72.9±8.5 years) from the PROTECT AF and PREVAIL studies. Both RCTs compared LAA closure with the Watchman device (Boston Scientific) to warfarin therapy in patients with nonvaluvular A-fib.

In both trials, the Watchman arm continued warfarin and aspirin for approximately 6 weeks postprocedure and then underwent transesophageal echocardiography. If adequate LAA sealing was confirmed, warfarin was discontinued and patients were treated with aspirin and clopidogrel for 6 months followed by indefinite aspirin therapy.

Watchman Advantage Beyond Perioprocedural Period

At baseline, mean CHA2DS2-VASc score was 3.7, and the mean modified HAS-BLED score was 1.9. Most patients (95.6%) had a CHA2DS2-VASc score ≥ 2, and 22.1% had a modified HAS-BLED score ≥ 3. Major bleeding was an adverse event, but not a prospectively defined endpoint in either trial.

At a median of 3.1 years, the overall rate of major bleeding was similar for the Watchman device compared with warfarin (RR 0.96; 95% CI 0.66-1.39).

However, nearly half of the bleeding events in the Watchman group (48%) occurred within the first 7 days after randomization (periprocedural period). Post-hoc analyses beyond that time period showed that LAA closure was associated with a reduction in major bleeding compared with chronic warfarin, with greater reductions seen with longer time from randomization.  

The findings remained consistent after adjusting for age, sex, baseline bleeding risk, and thromboembolic risk score. The relative magnitude of benefit was greater in women than in men (P = .02), in patients 75 years of age and younger compared with those over 75 (P = .005), and in those with modified HAS-BLED scores < 3 vs 3 or higher (P = .001).

According to the study authors, since the risk of major bleeding with oral anticoagulants is expected to persist or increase with age, the fact that the overall major bleeding rates were similar with closure and warfarin still argues for improved safety with the Watchman. They add that longer follow-up “seems likely to favor LAA closure.”

Still Watching the Watchman  

But in an editorial accompanying the study, John A. Bittl, MD, of Munroe Regional Medical Center (Ocala, FL), says the primary bleeding outcomes “are disconcerting, given that the rationale for using Watchman implantation in place of long-term warfarin is to reduce bleeding, and the post hoc subgroup comparisons that eliminate periprocedural bleeding from the comparisons should be viewed as biased to favor use of the Watchman device.”

Without a doubt, the device has had a troubled journey to the clinical arena, and as Bittl notes, underwent data review 3 separate times by the FDA’s Circulatory System Devices Panel before an approval recommendation squeaked by in October 2014 by a vote of 6 to 5 in favor on the issue of risks vs benefits. But despite strong evidence of safety, the panel could not recommend in favor of efficacy. In March 2015, the FDA approved the Watchman for prevention of stroke in warfarin-eligible patients.

According to Bittl, the device “fills an important clinical need and, despite concerns about how bleeding was analyzed in well-executed clinical trials, should be considered on a selective basis for high-risk patients with [non-valvular A-fib] who cannot tolerate long-term warfarin therapy.”

However, he adds that before LAA closure is contemplated as a routine procedure in this patient population, more study is needed to determine if the device actually does lower the risk of bleeding compared with warfarin. 
   

Sources:
1. Price MJ, Reddy VY, Valderrábano M, et al. Bleeding outcomes after left atrial appendage closure compared with long-term warfarin: a pooled, patient level analysis of the WATCHMAN randomized trial experience. J Am Coll Cardiol Intv. 2015;Epub ahead of print.
2. Bittl JA. Go set a Watchman? [editorial]. J Am Coll Cardiol Intv. 2015;Epub ahead of print.  

Related Stories:

• Good News, Bad News Week for Watchman LAA Occluder
• Is Watchman Cost-effective? That Depends Where You Look
• After Years of Scrutiny, Watchman Ready for Prime Time