Experts Discuss Efficacy, Safety of Watchman Device

San Francisco, CA—As the Watchman left atrial appendage (LAA) closure device (Atritech/Boston Scientific Corporation) moves closer to FDA approval for the treatment of atrial fibrillation (AF), two experts at TCT 2013 discussed important efficacy and safety issues with the available data.

“PROTECT AF was the first study to demonstrate that LAA closure was noninferior to long-term anticoagulation in the prevention of [AF and] stroke,” Saibal Kar, MD, of Cedars-Sinai Medical Center, Los Angeles, said. Four other studies have been conducted with the Watchman device (see Figure).

“The issue of safety vs. efficacy continues to bedevil us,” said David R. Holmes Jr., MD, of the Mayo Clinic.

Efficacy issues

The best-available randomized efficacy data come from PROTECT AF, Holmes said. Findings reported at the 2013 Heart Rhythm Society Annual Scientific Sessions demonstrated primary efficacy event rate (stroke, CV death and systemic embolism) per 100 patient-years with the Watchman device compared with warfarin alone at 60-month follow-up (2.3% vs. 3.8%; RR 0.60; 95% CI 0.41-1.05).

Holmes noted several roadblocks regarding efficacy, including training, approval of new oral anticoagulants and regulatory interest in an alternative trial of patients contraindicated for anticoagulation. Specific trial design — noninferiority vs. superiority, confidence intervals, and overlap of safety and efficacy endpoints — as well as specific patient populations and exclusions, such as those taking clopidogrel (Plavix, Sanofi-Aventis), have also been a cause for concern.

Despite roadblocks, Holmes said the totality of the Watchman data support both the efficacy and safety of this therapy.

Safety issues

Procedural safety of the device has improved during the clinical program, Kar said.

Primary safety events from PROTECT AF (1,065 patient-years) demonstrated a higher rate of adverse events per 100 patient-years of 7.4% with the device vs. 4.4% with control therapy (RR 1.69; 95% CI 1.01-3.19). “That was our Achilles’ heel,” Kar said. Early safety issues with the device included an unacceptable primary success rate, serious pericardial effusions (4.8% vs. 0%), procedure-related ischemic stroke (1.1% vs. 0%) and device embolization (0.6% vs. 0%). There were no late adverse events with the device, he added.

Specific steps were taken to prevent further complications, Kar said, such as proper device sizing and use of a pigtail catheter. Improvements have since been observed and confirmed in the CAP registry and PREVAIL trial, including shorter implant time, better implant success, higher warfarin discontinuation and fewer procedure- and device-related events.

Operator experience was also addressed in PREVAIL, as the FDA mandated that 25% of procedures had to be performed by new operators at new sites. Eighteen of 41 PREVAIL centers had no prior device experience and 40% of patients were enrolled at new sites by new operators. Results indicate that safety was met with improved procedural safety irrespective of operator experience, he said. 

Disclosures:

Holmes and Kar report conflicts of interest with several device and pharmaceutical manufacturers.