The Watchman device, approved for routine use by the Food and Drug Administration in March, gives U.S. atrial fibrillation patients their first alternative to chronic anticoagulant treatment for preventing ischemic stroke.
By closing off the sac-like left-atrial appendage (LAA) with Watchman – a plug-like device placed via percutaneous, transcatheter delivery – blood clots cannot form in the LAA, thereby eliminating the source for most of the thrombi that threaten to cause ischemic strokes in patients with atrial fibrillation (AF).
But while many cardiologists welcome this new option that, for the first time, gives AF patients a way to avoid years or even decades of daily treatment with an anticoagulant, U.S. rollout of the device out has not been seamless. In many regions, health insurers have been unwilling to cover payment for Watchman and its placement, say physicians. Medicare AF patients in particular have been in a state of limbo for receiving a Watchman device while the Centers for Medicare and Medicaid Services (CMS) makes a national coverage determination, a decision not expected until later this year.
In addition, the AF patients who arguably are the best candidates for receiving this device are technically ineligible based on Watchman’s labeling as well as a very limited evidence base. The FDA approved the device specifically for patients judged “suitable for warfarin,” a decision driven largely by the two Watchman trials that led to approval. Each of these trials randomized warfarin-eligible patients either to receive the device along with a 6-week course of warfarin following placement to ensure against acute thromboembolic complications, or to chronic warfarin treatment with no device.
Although this design allowed head-to-head comparison between Watchman and the traditional standard for anticoagulation in AF patients, it left unaddressed the question of how Watchman performs in the AF patient population with the most obvious indication for a mechanical solution to stroke risk: patients who are completely intolerant of anticoagulation treatment. By strict labeling criteria those patients, desperate for an effective means to reduce their stroke risk, are ineligible to receive Watchman.
“It’s approved for patients who can take warfarin, and that’s wrong,” said Dr. Peter R. Kowey , an AF specialist and professor and director of the Center for Clinical Cardiology at the Lankenau Institute for Medical Research in Wynnewood, Pa. “Most of us in clinical practice believe Watchman has the potential to help patients who would be difficult to anticoagulate long term. This is how it’s used around the world.”
Who should get Watchman right now?
With patients with contraindications for anticoagulants excluded by current labeling, who are the right patients to get this device, especially with long-term experience still relatively limited? Many AF experts say they currently see targeting it to AF patients who are clearly at high risk from both stroke and anticoagulation, as well as possibly also patients who face less of a risk from an anticoagulant treatment but express a strong dissatisfaction with having to remain on such therapy for the rest of their lives.
The Watchman-trial results “were quite compelling, and the device fills a large, unmet need for patients who are inappropriately treated or undertreated” with anticoagulation, said Dr. J. Peter Weiss , an electrophysiologist at the Intermountain Heart Institute in Salt Lake City. “The data show it’s as good as warfarin for preventing ischemic stroke, and the 5-year outcome data [from the PREVENT AF trial] showed a survival advantage largely based on a reduced rate of hemorrhagic stroke” compared with patients on warfarin. “The benefit from Watchman is not just in preventing ischemic strokes,” Dr. Weiss said in an interview.
Researchers presented the 5-year outcomes from PROTECT AF to the FDA in October 2014, and while those results remain unpublished, Dr. Shephal K. Doshi , director of cardiac electrophysiology at Saint Johns Health Center in Santa Monica, Calif., presented them at the Heart Rhythm Society annual meeting in Boston in May. The 5-year outcomes showed that compared with patients treated chronically with warfarin, those who had received a Watchman device had a 39% relative risk reduction for the study’s primary, combined endpoint, a 32% relative risk reduction in the incidence of all strokes, and a 56% statistically significant relative risk reduction in cardiovascular deaths plus unexplained deaths. The 4-year follow-up results from PROTECT AF, with a similar mortality advantage for Watchman over warfarin, were published last year ( JAMA. 2014 Nov. 19; 312[19]:1988-98 ).
The patients who could benefit the most from receiving a Watchman device fall into two categories, Dr. Weiss said: AF patients at high risk for both stroke and bleeding, identified by their high scores on both the CHA2DS2-VASc and HAS-BLED formulas, and relatively young AF patients with a high CHA2DS2-VASc score who face the prospect of receiving warfarin or another anticoagulant for a long period of time, possibly several decades. An AF patient who is, for example, 66 years old may have a moderate risk for a serious bleeding event of about 0.5%/year on warfarin or a new oral anticoagulant (NOAC) such as apixaban ( Eliquis ), dabigatran ( Pradaxa ), edoxaban ( Savaysa ), or rivaroxaban ( Xarelto ), but if that patient were to live for 20 years, the cumulative risk for a major bleeding event could be about 10%, he noted.
Dr. Gordon F. Tomaselli , an electrophysiologist, professor of medicine, and chief of cardiology at Johns Hopkins University in Baltimore, envisions a similar target population: “People who cannot or will not take warfarin or a new oral anticoagulant,” he said. He cited AF patients with a CHA2DS2-VASc score of at least 2, but perhaps in most cases for serious Watchman consideration with an even higher CHA2DS2-VASc score and hence an even greater stroke risk, as well as an inability to received optimal anticoagulant-drug treatment.
“Right now Watchman fills a small but important niche. If a patient is eligible for an oral anticoagulant and not especially averse to taking one I’d go with that, especially if the patient does not closely resemble those enrolled in the trials, because our experience with NOACs is quite good. But once we get good at placing Watchman and our experience grows, you’ll start to see the indications expand,” he predicted.
Dr. Saibal Kar , director of interventional cardiology research at Cedars-Sinai Medical Center in Los Angeles and a lead collaborator on the Watchman pivotal trials, agreed that for the time being as well as the foreseeable future Watchman remains a “second-line” option for patients who clearly fail the first line of treatment with warfarin or a NOAC (although Dr. Kar still prefers warfarin). “I absolutely start patients on warfarin and see how they do” and then he offers Watchman to patients who “for various reasons cannot take warfarin or a NOAC,” which could mean serious bleeding episodes or a clear pattern of noncompliance, Dr. Kar said in an interview. Some patients also opt for Watchman because of lifestyle issues, such as a history of falls, or patients who engage in potentially bruising sports such as skiing, he said.
Dr. Kar highlighted the evidence that with longer follow-up, Watchman is not only comparable to warfarin for safety and efficacy, the endpoint specified in the pivotal trials, but also showed a strong signal for long-term superiority in the 4- and 5-year results from PROTECT AF. “For a lot of patients who have challenges [with bleeding complications] Watchman is a great option. When you prevent life-threatening bleeds, it translates into a mortality benefit.”
A cautionary view for the current role of Watchman came in a June editorial written by two physicians at Beth Israel Deaconess Hospital in Boston, who warned that in selected patients Watchman “may be safe, effective, and preferable to chronic warfarin thromboembolic prophylaxis in AF, but at this point many questions surrounding its safety and long-term efficacy remain unanswered” ( J Am Coll Cardiol. 2015 June 23;65[24]:2624-7 ). Dr. Jonathan W. Waks and Dr. Warren J. Manning went on to say in their commentary that “at this point in time, it appears that patients treated with Watchman may pay early (procedural complications) and may also possibly pay later (late thromboembolism).”
In a reply to this critique, Dr. David R. Holmes Jr. , professor of medicine and an electrophysiologist and interventional cardiologist at the Mayo Clinic in Rochester, Minn., and developer of the Watchman device, countered that while extremely long-term outcomes from Watchman, beyond 5 years, are not yet available, the long-term consequences of extremely prolonged chronic anticoagulation that continues for a similarly extended period also remain undocumented. He noted that hemorrhagic stroke poses the greatest stroke danger to patients maintained on anticoagulant therapy, but the meta-analysis of Watchman results that he and his associates published in June – the article that was the subject for the comment by Dr. Waks and Dr. Manning – showed a 78% relative risk reduction in hemorrhagic strokes among Watchman recipients compared with control AF patients who received warfarin ( J Am Coll Cardiol. 2015 June 23;65[24]:2614-23 ).
Dr. Holmes acknowledged that patients treated with Watchman and no anticoagulant can develop ischemic strokes from causes aside from clot formation in the LAA. But he stressed that the meta-analysis he published in June showed a striking 52% relative decrease in cardiovascular or unexplained deaths during and average 2.7 years of follow-up compared with the control patients treated with warfarin.
“It is extraordinarily uncommon to have this magnitude of improved survival in a relatively small number of patients,” and the survival benefit was consistent across both randomized Watchman trials as well as in both continued access cohorts that followed each of the two trials, Dr. Holmes said in an interview.
“I fully accept that we don’t have data beyond 5 years, but the data from PROTECT AF out to 5 years showed no evidence of late strokes or other adverse events,” said Dr. Vivek Y. Reddy , professor of medicine and director of the cardiac arrhythmia service at Mount Sinai Hospital in New York. “In fact, the longer you follow these patients [who received Watchman], the more benefit you see, because these patients are not on an oral anticoagulant long term. Concern about long-term outcomes “is not borne out in the data,” said Dr. Reddy, another leader of the team of interventionalists and electrophysiologists who ran the Watchman trials.
“If a patient with AF comes to me and says ‘I don’t want to take the damn anticoagulants, I want a Watchman,’ and if the patient understands the risks and benefits of Watchman, then I’m 100% fine” facilitating placement of the device in such a patient, explained Dr. Kowey, someone who remains very skeptical of Watchman’s current track record and role. “But what should not happen is for physicians to try to sell Watchman to their patients. Physicians should not tell patients that you don’t need to worry about anticoagulation anymore because I can put in a Watchman and it’s the end of the story. We’re very short of having enough information right now to recommend it to patients” this way. Despite this information shortfall, “I know for a fact” that this sort of promotion of Watchman occurs right now from physicians with an economic incentive to place the device into patients, Dr. Kowey said in an interview.
While some physicians may excessively promote Watchman, they also likely have a receptive audience. “I don’t think it will be hard to find patients who are interested in the device. The challenge will be to figure out if a patient is a good candidate,” said Dr. Paul Varosy , director of electrophysiology at the Denver VA Medical Center. “I have patients and physicians who ask all the time when we will start making the device available. I care for many patients who absolutely despise warfarin and NOACs, and they would love to have a way to get off their medication that does not involve having a risk for a massive stroke,” he said. “What is striking to me is how many patients are interested in this device without being aware of what they would be getting.”
Paying for Watchman
Economic incentives for placing Watchman into patients aside, paying for the device right now and for the procedure that’s involved is no easy matter. Several cardiologists active in Watchman programs scattered around the United States report substantial problems encountered since March with health insurance coverage for the device and placement procedure, and they add that uncertainties about coverage or denied coverage has significantly limited the number of patients who have received the device.
One of the more glaring examples is at the Mayo Clinic in Rochester, Minn., the program led by Dr. Holmes, who helped develop the Watchman technology. He and his associates have placed roughly 20 of the devices since March, but in August he said that his program had “about 40-50 patients” who had been fully screened for the device and looked like they were excellent candidates but were refused coverage by their health insurers. And after some of the 20 patients had already received a Watchman at Mayo, their insurers denied payment, cases that now are on appeal, Dr. Holmes said.
Other active programs report similar difficulties. Dr. Reddy said his program had placed Watchman into about 30-35 patients through the end of August, and while “a majority” of his candidate patients received authorization from their health insurers, others have not received authorization and are on appeal. Insurance coverage is “clearly a problem,” he said in an interview.
Dr. Kar said his Cedars-Sinai program in Los Angles has put Watchman into about 55 patients since last March, and the pace recently accelerated with his treating 13 patients during a 2-day period in August, but he has also seen “lots of problems with insurance,” with appeals usually needed on a case-by-case basis. “We’ve had several appropriate patients who have not received the device because they were not covered,” although most of those cases remain on appeal.
At the University of Kansas in Kansas City, “reimbursement issues have been a major hindrance to widespread use of the device,” and has so far limited placement to just a few patients, said Dr. Dhanunjaya R. Lakkireddy , professor of medicine and director of the University’s Center for Excellence in AF and Complex Arrhythmias. At the Intermountain Heart Institute in Salt Lake City, operators have done just 3 placements since the device’s approval, after doing 128 Watchman placements during the trials and continued access programs. One of the patients paid for the device and procedure completely out of pocket, said Dr. Weiss, a bill that Dr. Kar said runs more than $20,000. The second of the Intermountain patients received Medicare coverage, and in the third case “we met with CMS and are waiting to hear,” Dr. Weiss said. “We are being very cautious to do cases that are very well indicated” to help better ensure that they will receive medical insurance coverage, Dr. Weiss said in an interview.
In May, the CMS began a National Coverage Analysis for Watchman prompted by a request from the device’s manufacturer, Boston Scientific. The appeal for Medicare coverage received support in a June letter written by the presidents of the American College of Cardiology, the Heart Rhythm Society, and the Society for Cardiovascular Angiography and Interventions.
A national coverage determination by the CMS in favor of paying for Medicare patients who undergo Watchman placement “would be a huge benefit,” said Dr. Holmes, who predicted that private insurers would then follow the CMS’ lead and cover the procedure as well. The CMS set Nov. 21, 2015, as the deadline for its decision.
Patients with anticoagulant contraindications will take more time
Even if the CMS decides in favor of reimbursing Watchman placement, the request that it received from Boston Scientific specified coverage for the FDA-approved indication, which stipulates placement in patients able to undergo warfarin treatment. That means for patients who are unable to receive anticoagulant treatment, placement constitutes off-label use that will likely remain unreimbursed, yet these are the very patients that experts agree form an obvious target for Watchman intervention. Currently, these AF patients generally rely on chronic aspirin treatment as their only protection against ischemic stroke.
The only formal, reported experience using Watchman in AF patients who did not also receive warfarin during the first 6 weeks following placement came in a 150-patient, uncontrolled feasibility study, ASAP (ASA Plavix Feasibility Study With WATCHMAN Left Atrial Appendage Closure Technology) run at four centers in Europe ( J Am Coll Cardiol. 2013 June 25;61[25]:2551-6 ). All of the enrolled patients were ineligible to receive warfarin, and instead following Watchman placement these patients received either clopidogrel or ticlopidine for 6 months and chronic treatment with aspirin (dual antiplatelet therapy [DAPT]). Follow-up averaged 14 months, and based on the patients’ average CHA2DS2-VASc score at entry the expected annualized rate of ischemic stroke in these patients was roughly 7%.
However, their observed rate was just 1.7%, and their rate of periprocedural and postprocedural complications roughly matched the rates seen in the first Watchman randomized trial. The researchers who ran the study concluded that the results showed that “Watchman can be safely implanted without a warfarin transition.”
Although the ASAP results showed “Watchman is very effective for stroke prevention” without early anticoagulation following placement, “I’m not sure how one could use Watchman for patients contraindicated for oral anticoagulation,” said Dr. Lakkireddy. “This is a controversial area, and one has to be cautious about cavalier off-label use of the device.”
“I think we need to know more about the [ASAP] data before we’d feel comfortable offering the Watchman device” to patients contraindicated for oral anticoagulation, said Dr. Weiss.
Patients with a total contraindication against treatment with warfarin or a NOAC have the greatest need, said Dr. Reddy. “The problem is, we don’t have much safety data” for these patients, and while the results from the ASAP trial showed the device can be safely placed just using DAPT, the numbers were small and the device is not approved” for use in this setting, said Dr. Reddy, the lead investigator for the ASAP study.
The solution to the dilemma posed by this patient group may lie in the ASAP 2 study, a large, multicenter trial that will enroll AF patients with a contraindication to oral anticoagulation and will compare Watchman placement followed by several months of antiplatelet treatment with DAPT head-to-head with patients randomized to today’s standard treatment of aspirin only. The trial will be sponsored by Boston Scientific, and should start by the end of this year, Dr. Reddy said. He envisions enrolling many of the AF patients he sees with an absolute contraindication to oral anticoagulant treatment in the trial once it starts, though it will mean that only half the enrolled patients will receive a Watchman device.
Dr. Holmes sees registry data as another possible route for eventually expanding the labeled indication for Watchman to patients who can’t receive warfarin or another anticoagulant. He cited the precedent of the FDA broadening the labeled indication for transcatheter aortic-valve replacement in 2013 based in part on U.S. registry data as well as on data collected in Europe.
One potential source of U.S. patients who could wind up receiving only brief warfarin treatment after Watchman placement would be those who develop a major bleed soon after starting on anticoagulation, an event that would prompt most physicians to discontinue and not restart warfarin, Dr. Holmes said. He suggested that in these circumstances patients receive DAPT for 6 months using aspirin and clopidogrel, following the protocol tested in ASAP.
The likely source of registry data would be the database that will be created and maintained by the ACC according to an announcement from the ACC in August. This registry is seen by the ACC as addressing the need for a postapproval safety and efficacy assessment of 1,000 U.S. Watchman recipients that the FDA mandated as part of its device approval last March.
“The registry will function as the postapproval study mandated by the FDA,” said Dr. Varosy of Denver, who led the effort to develop and structure the ACC’s Watchman registry. One goal of the registry “will be to get a better understanding of how the device performs” in patients who can’t take an anticoagulant. “I think that’s where the strongest rationale is for having a device like this,” he said. “It would be great to do something for patients who can’t take warfarin, but until we have data for that group we’ll just have to wait.”
Recommendations detail appropriate Watchman rollout
A recent review of LAA occlusion-device options by the ACC, Heart Rhythm Society, and Society for Cardiovascular Angiography and Interventions was an attempt by these three U.S. professional societies with a stake in AF management and LAA closure to “address issues critical to the appropriate integration of new technologies into the care of patients with AF” ( J Am Coll Cardiol. 2015. doi:10.1016/j.jacc.2015.06.028]). One of the review’s most notable features is a section that makes specific recommendations about the composition of the physician team that assesses prospective AF patients for LAA closure and performs the procedure. The document suggests the process involve a team of physicians with expertise in electrophysiology, cardiac catheterization, stroke prevention, echocardiography, x-ray imaging, and possibly anesthesiology if general anesthesia is planned. The panel also recommended having a cardiac surgeon on hand for surgical backup if needed. The review also made recommendations on the facilities needed to safely and effectively perform LAA occlusion, the training that should be in place for the operator who performs the procedure, the protocols that should exist to guide patient management before, during, and after occlusion, the methods used to select AF patients for LAA occlusion, and the need for a U.S.-based LAA registry.
Despite these recommendations, “it is currently too early to tell how Watchman will be introduced into practice with respect to facilities, training, etc.,” Dr. Frederick A. Masoudi , a cardiologist at the University of Colorado in Denver and chair of the review committee, said in an interview. The three professional societies “are separately releasing a statement that focuses in greater detail on recommended operator characteristics and training.” This statement is still pending, he said.
A spokeswoman for Boston Scientific said that the company “supports the recommendations [from Dr. Masoudi’s committee], which are very much in line with our established criteria for new implanting centers. We are committed to the rational dispersion of the technology through a disciplined and highly selective approach to center identification. We will ensure that all implanters and implanting centers meet specific prerequisites including appropriate facilities and a dedicated and experienced team to perform the procedure. In addition, we will require implanters and echocardiographers to complete a rigorous clinical training program.”
As of late August, Boston Scientific identified on its website 32 U.S. centers performing LAA closure using Watchman. The company anticipates that about 100 U.S. centers will be performing the procedure by the end of 2015.
The PREVENT AF and PREVAIL pivotal trials for Watchman and their subsequent continued-access programs were sponsored by Boston Scientific. Dr. Kowey has been a speaker for Boston Scientific and has consulted for several drug companies that market anticoagulants. Dr. Weiss has been a speaker for Boston Scientific and also for St. Jude, Biosense Webster, and Stereotaxis. Dr. Kar has received research grants from Boston Scientific and served as principal investigator for the two continued-access programs that followed the two Watchman pivotal trials. He has also received research grants from Abbott Vascular and St. Jude, and has an equity interest in Coherex. Dr. Holmes and the Mayo Clinic have a financial interest in technology related to Watchman and this technology was licensed to Boston Scientific. Dr. Reddy has been an adviser to and received research grants from Atritech/Boston Scientific. Dr. Lakkireddy, Dr. Varosy, Dr. Masoudi, and Dr. Tomaselli had no disclosures.
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