Boston Scientific Corp.’s Watchman device, designed to help prevent strokes in patients with an erratic heartbeat, was safer than previously thought in a second study requested by U.S. regulators, researchers said.
The company said the results, originally intended to be presented today at the American College of Cardiology’s meeting in San Francisco, show the device can be safely used and plans to request FDA approval. Heart meeting officials canceled the presentation after Boston Scientific inadvertently distributed results of the study, known as Prevail, to investors before the data was slated for presentation at the meeting.
The device is threaded into the heart and used to block off a reservoir where blood can pool, forming clots that cause strokes. The procedure itself triggered strokes, clots or major complications in 2.2 percent of patients within a week, an acceptable risk in return for helping patients avoid the need for daily blood thinners, said lead researcher David Holmes, a cardiologist at the Mayo Clinic in Rochester, Minnesota.
“This takes care of the safety issues,” and there was great concern about its safety, Holmes said in an interview yesterday. “By virtue of the fact that it confirms the efficacy, I think it’s a real step forward,” he said, declining to predict how U.S. regulators will rule on the device.
The U.S. Food and Drug Administration requested the new trial in 2009 after refusing to approve the device because the initial study showed an unacceptably high rate of complications. The study involved 252 patients treated with the Watchman and 138 who were given the blood thinner warfarin as a comparison.
The company created controversy earlier this week when it said it would show only limited safety information from the trial, then reversed the decision. It updated the official registration for the device on the U.S. government’s clinical trials website on March 1. The update changed the study description to include a safety review, altered the single main goal to make it three separate objectives and moved the six-month time period of the study to two time points at one week and 18 months.
The size, length and design of the study, not to mention changing the official record, all raise serious concerns about whether the Watchman should be used, said Steven Nissen, chief of cardiology at the Cleveland Clinic in Ohio. There were fewer than 100 patients followed out to 18 months, making any analysis suspect, he said.
“This study doesn’t stand the sniff test,” he said in an interview at the meeting. “How much can you know about the safety with 100 patients?” he asked. “It is extremely difficult to see how this device could be approved by the FDA under the circumstances as we currently understand them.”
A preliminary analysis of how effective the device was after 18 months yielded mixed results. It failed to show the Watchman was as good as the blood thinner warfarin at heading off strokes, clots and death after 18 months, though it was similar when researchers excluded the first week’s results.
The results of the study were funded by Natick, Massachusetts-based Boston Scientific. Both Holmes and the Mayo Clinic have a financial interest in the technology, which they licensed to Atritech Inc.
The company plans to submit the findings, plus updated results from its initial Protect AF trial and other research, to the U.S. regulators to support Watchman’s approval, said Ken Stein, chief medical officer of the company’s cardiac rhythm management group.
“We are really optimistic about this,” Stein said in a telephone interview. “We see it as fitting a huge patient need and having a huge amount of data to support it. We see it as an adjacent technology to what has been our core business.”
Boston Scientific officials have estimated the potential market for the device used to close the left atrial appendage could reach $500 million within five years. The Watchman competes against St. Jude Medical Inc.’s Amplatzer cardiac plug in Europe, where both are already approved. St. Jude, based in St. Paul, Minnesota, said it started a study of its product this week that it will use to try to obtain U.S. approval.
The researchers used a controversial new design for the study, which involves predicting the future rates of strokes and other complications based on adding the findings from the new investigation to the results of previously conducted research. The complex analysis, known as the Bayesian piecewise exponential technique, was requested by the FDA, Holmes said. While the approach hasn’t been used previously in such a high-profile trial, Holmes said he expects it to become more common.
“People are becoming more comfortable with Bayesian analysis,” he said. “In the future, I think we will see more of that.”
The technique is designed to find information more quickly with fewer patients, Holmes said. The approach allowed the researchers to draw conclusions from the data, even though they had 18 month information from only 58 patients who received the device and 30 patients in the control group getting warfarin.
The previous trial showed 8.7 percent of patients in the study suffered vascular complications within seven days, including perforating the heart, having the device migrate from the location where it was implanted, blood buildup around the heart, bleeding near the groin where the catheter was inserted and stroke. In the new study, complications were 4.4 percent, when using the same set of criteria.
The earlier trial, dubbed Protect AF, found the device worked as well as warfarin, though patients undergoing the surgery were significantly more likely to have complications. Regulators were particularly concerned that physicians new to the technique would have higher complication rates. The newest cardiologists had the best results in the Prevail trial.
Boston Scientific acquired the Watchman technology when it bought closely-held Atritech in 2011 for $100 million, with another $275 million in potential payments linked to regulatory and sales-based milestones.