Watchman Thrombi 'Not Infrequent,' May Cause Strokes

Be careful out there if you are trying to use it for atrial fibrillation.

Timing suggests causation in at least half of strokes with device-related thrombi

• Crystal Phend, Senior Associate Editor, MedPage Today May 13, 2018

BOSTON -- Watchman device-related thrombi developed in 3.7% of patients and appeared temporally-related to strokes, meta-analysis of clinical trials and registries showed.

The annualized stroke rate across the 1,739 patients in the PROTECT-AF and PREVAIL trials and two continued access program registries was 1.77%, among which 10.2% occurred in patients found to have device-related thrombi (DRT), Vivek Reddy, MD, of Icahn School of Medicine at Mount Sinai in New York City, reported here at the Heart Rhythm Society (HRS) meeting and online in Circulation.

The expected ischemic stroke rate for the same CHA₂DS₂-VASc score, based on the literature, would be 6.0% for untreated patients and 1.71% on oral anticoagulants, Reddy noted at the late-breaking clinical trial session.

Antithrombotic use data for the Watchman cohorts was not known, although the FDA trials recommended warfarin and aspirin for the first 6 weeks, followed by clopidogrel (Plavix) and aspirin to 6 months and aspirin alone thereafter.

Clots can form on any foreign body, and Watchman studies have shown only thin endothelialization at 200 days after implantation and the metal screw still visible in cadaver specimens even at 852 days, said HRS discussant David De Lurgio, MD, of Emory Saint Joseph's Hospital in Atlanta, who called that "kind of scary."

A timeline analysis trying to get at causation showed that about half of strokes in Watchman patients did co-localize within 1 month of finding thrombus on the device, "which suggests at least half of patients' DRT is causing stroke," although other stroke risk factors are playing a role too, Reddy said.

When DRT was found on study-mandated repeat transesophageal echocardiography (TEE), the risk of stroke or systemic embolism was 3.55-fold elevated overall and 3.2-fold elevated for ischemic stroke specifically. However, no significant association with mortality emerged.

"So putting this all together I think there are a couple of things: First, it's clear that DRT is not that frequent but it's also very clear that when it occurs it increases the risk of subsequent ischemic stroke," Reddy concluded. "Two: It's an important clinical issue, what do we do with patients who have DRT? ... We don't have any prospective data to make absolute recommendations.

"But minimally, we believe that if DRT is detected, we need to have an aggressive surveillance regimen afterward with transesophageal echo or CTA."

As to the surveillance regimen more broadly, the FDA approval mandated TEE at 45 days and 1 year.

In the meta-analysis, comparing the registries (which mandated TEE at 45 days and 12 months) to the trials (which added a TEE at 6 months) showed a non-significant trend for more DRT capture with the additional TEE but no difference in ischemic stroke or systemic embolism.

The strategy Reddy said he favors would be to delay the first TEE to 3 to 4 months post-implantation, rather than adding a third intermediate procedure.

"There doesn't appear to be anything we know to do right now" to get rid of the problem, such as increased training, De Lurgio noted. "There's a big question, When are we out of the woods?"

Anecdotally, Reddy said his practice is to treat Watchman patients with a non-vitamin K antagonist oral anticoagulant and that DRTs don't usually emerge until after stopping anticoagulation. In the meta-analysis, some DRTs first showed up at the 1 year TEE.

Reddy cautioned that the findings may only apply to patients treated with the specific post-implantation antithrombotic regimen used in the studies and not to other types of left atrial appendage occlusion devices, although "the general concepts raised are likely applicable to other devices."

PROTECT AF, PREVAIL, CAP, and CAP2 studies were funded by Boston Scientific.

Reddy disclosed relevant relationships with Boston Scientific, Abbott, Biosense-Webster, and Surecor.

De Lurgio disclosed relevant relationships with Boston Scientific.

last updated 05.13.2018

• Primary Source

  Circulation

  Source Reference: Dukkipati SR, et al "Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes" Circulation 2018; DOI:10.1161/CIRCULATIONAHA.118.035090.

LAAC Device Reduces Risk of Stroke in Patients With or Without Contraindication to Oral Anticoagulation

To discuss with your doctor.
http://dgnews.docguide.com/laac-device-reduces-risk-stroke-patients-or-without-contraindication-oral-anticoagulation?

May 16, 2017

By Louise Gagnon
CHICAGO -- May 16, 2017 -- Left atrial appendage closure (LAAC) with an implantable device was successful in reducing the risk of stroke in patients with non-valvular atrial fibrillation (AF), with or without contraindication to oral anticoagulation, according to a study presented here at the 38th Annual Scientific Sessions of the Heart Rhythm Society (HRS).
“The device is a permanent implant designed to close the left atrial appendage in the heart in an effort to reduce the risk of stroke,” explained Lucas V. A. Boersma, MD, St. Antonius Ziekenhuis Hospital, Nieuwegein, the Netherlands.
The researchers examined data from 1,025 patients with non-valvular AF (mean age, 73 years) who had the WATCHMAN device implanted.
There was implant success in 98.5% of patients and 91% of active patients had been followed for at least 11 months.
The majority of patients (~73%) were not taking anticoagulants because of a history of major bleeding.
Co-morbidities were common in the study population and included diabetes, hypertension, congestive heart failure, and a history of haemorrhagic and ischaemic stroke.
“The expected stroke rate in this population is 7.2% and the actual stroke rate was 1.2%, giving us a relative risk reduction of 84%,” said Dr. Boersma.
Similarly, the implant reduced the risk of bleeding in patients. Thrombus of the device developed in 27 patients, and it occurred regardless of use of anticoagulants.
“One of the concerns may be the development of device thrombus,” said Dr. Boersma. “We did not find a correlation between patients having thrombus and the lack of use of anticoagulant medications.”
The 1-year mortality was 9.8%, but Dr. Boersma said the mortality was not attributable to the implantation of the device but rather the health status of the patients.
Funding for this study was provided by Boston Scientific Corporation.
[Presentation title: EWOLUTION Trial: 1-Year Efficacy and Safety of Left Atrial Appendage Closure With WATCHMAN in Patients With or Without Contraindication to Oral Anticoagulation. Abstract C-LBCT02-03]

Early Watchman Experience Reassuring, But Many Questions Remain

Is your doctor good enough not to have problems with installing this device? Better than the success rate for tPA use and full stroke recovery?
http://cardiobrief.org/2016/11/04/early-watchman-experience-reassuring-but-many-questions-remain/
One paragraph;
In addition to the 95.6% rate of successful implantation, Reddy and colleagues reported a median procedure time of 50 minutes. About half of the procedures were performed by physicians who were not involved in Watchman clinical trials. There were 39 cases of pericardial tamponade, three procedure-related strokes, 9 device embolizations, and 3 procedure-related deaths.

Study of First-in-Class WATCHMAN® Device Shows 75 Percent Reduction in Stroke Risk in Patients with Atrial Fibrillation Not Eligible for Oral Anticoagulation Therapy

Another A-fib option to ask your doctor about. From the African Business Review.
http://www.africanbusinessreview.co.za/press_releases/study-of-first-in-class-watchman-device-shows-75-percent-reduction-in-stroke-risk-in-patients-with-a
 Boston Scientific Corporation (NYSE: BSX) announces results from the ASA Plavix (ASAP) Study, which studied the WATCHMAN® Left Atrial Appendage Closure (LAAC) device.  The data showed a reduction in the risk of ischemic stroke by 75 percent in patients with atrial fibrillation who have a contraindication to oral anticoagulants such as warfarin.  Vivek Reddy, M.D., Director of Cardiac Arrhythmia Service at Mount Sinai Medical Center in New York and Coordinating Investigator of the study presented results today during a late-breaking session at the Heart Rhythm Society's 33rd Annual Scientific Sessions in Boston.
The prospective multi-center ASAP Study evaluated 150 patients with contraindications to warfarin, who were implanted with the WATCHMAN Device and treated with dual antiplatelet therapy for six months post-procedure.  Subjects were followed for a mean average of 14.4 months.  The study employed the widely recognized CHADS2 risk stratification score, which provides a clinical prediction tool for estimating the risk of stroke in patients with atrial fibrillation.  The CHADS2 score has been validated by numerous studies and is regularly used to determine whether treatment is required with anticoagulation or antiplatelet therapy.
"WATCHMAN is the most studied LAA closure device with more than 2,000 patients enrolled in prospective studies and nearly 4,000 patient-years of follow up," said Keith D. Dawkins, M.D., global chief medical officer for Boston Scientific.  "This novel device has been well received in more than 30 countries where it offers a safe and effective alternative to long-term treatment with oral anticoagulants."
Atrial fibrillation affects approximately 15 million patients worldwide and is a disorder that disrupts the ability of the heart to beat regularly and pump blood efficiently.  Patients in atrial fibrillation are at greater risk for stroke due to the migration of clots formed in the left atrial appendage (LAA).  Anticoagulants such as warfarin have traditionally been the only therapy for reducing stroke risk in these patients.  The Boston Scientific percutaneously delivered WATCHMAN Device is an alternative to long-term anticoagulation in patients eligible for anticoagulant therapy.  It is designed to close the LAA, thereby preventing clots forming within the appendage and being dislodged into the bloodstream where they can potentially cause a stroke. 
"Findings from the ASAP Study are promising in that closure of the LAA with the WATCHMAN Device produced a significant reduction in the expected ischemic stroke rate for this patient population," said Dr. Reddy.  "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."
For patients in the ASAP Study, the average baseline CHADS2 score of 2.8 equated to a predicted ischemic stroke rate of approximately 7.1 percent per year.  The observed rate of ischemic stroke for patients implanted with the WATCHMAN Device was 1.7 percent per year, a 75 percent reduction in stroke risk from the predicted stroke rate based on the CHADS2 score (p<0.01).  The corresponding upper confidence bound yielded a stroke rate of 4.4 percent per year, lower than the predicted stroke rate of 7.1 percent. 
Stroke rates in the ASAP study were similar to those observed in the PROTECT AF study, which assessed similar subjects not contraindicated to warfarin.   In the multi-center, randomized PROTECT AF trial, the WATCHMAN Device proved to be non-inferior to warfarin and demonstrated a 38 percent relative risk reduction for stroke, cardiovascular death and systemic embolism compared to long-term warfarin therapy in 707 patients. 
The WATCHMAN Device was approved for marketing in Europe and other CE Mark countries in 2009.  Boston Scientific is currently enrolling U.S. patients in the PREVAIL study, a confirmatory study designed to gain U.S. Food and Drug Administration approval.  Enrollment is expected to be completed in the second quarter of 2012.  The WATCHMAN Device is contraindicated in patients who are not eligible for anticoagulation therapy.  In the U.S., the WATCHMAN Device is an investigational device, limited by applicable law to investigational use and not available for sale.  The device was developed by Atritech, which Boston Scientific acquired in March 2011.  For more information, visit www.Atritech.net.   
For more news about Boston Scientific at the Heart Rhythm Society 33rd Annual Scientific Sessions, please follow us on Twitter @BostonSci.
About Boston ScientificBoston Scientific is a worldwide developer, manufacturer and marketer of medical devices that are used in a broad range of interventional medical specialties.  For more information, please visit: www.bostonscientific.com.  
Cautionary Statement Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.  Forward-looking statements may be identified by words like "anticipate," "expect," "project," "believe," "plan," "estimate," "intend" and similar words.  These forward-looking statements are based on our beliefs, assumptions and estimates using information available to us at the time and are not intended to be guarantees of future events or performance.  These forward-looking statements include, among other things, statements regarding markets for our products and launch cadence, regulatory approvals, clinical studies, trials and outcomes, product performance and competitive offerings.  If our underlying assumptions turn out to be incorrect, or if certain risks or uncertainties materialize, actual results could vary materially from the expectations and projections expressed or implied by our forward-looking statements.  These factors, in some cases, have affected and in the future (together with other factors) could affect our ability to implement our business strategy and may cause actual results to differ materially from those contemplated by the statements expressed in this press release.  As a result, readers are cautioned not to place undue reliance on any of our forward-looking statements. 
Factors that may cause such differences include, among other things: future economic, competitive, reimbursement and regulatory conditions; new product introductions; demographic trends; intellectual property; litigation; financial market conditions; and future business decisions made by us and our competitors.  All of these factors are difficult or impossible to predict accurately and many of them are beyond our control.  For a further list and description of these and other important risks and uncertainties that may affect our future operations, see Part I, Item 1A – Risk Factors in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, which we may update in Part II, Item 1A – Risk Factors in Quarterly Reports on Form 10-Q we have filed or will file hereafter.  We disclaim any intention or obligation to publicly update or revise any forward-looking statements to reflect any change in our expectations or in events, conditions or circumstances on which those expectations may be based, or that may affect the likelihood that actual results will differ from those contained in the forward-looking statements.  This cautionary statement is applicable to all forward-looking statements contained in this document.

Technology To Prevent Stroke Demonstrated In JoVE

Practically anything would be better than rat poison. 

Technology To Prevent Stroke Demonstrated In JoVE

In the United States alone, approximately 6 million people suffer from an irregular heartbeat called atrial fibrillation (AF), and since the incidence increases with age, it is predicted that 15.9 million Americans will be affected by 2050. The most devastating side effect of AF is stroke, but a new device from Boston Scientific may prevent them from occurring.

Researchers from Atritech, now part of Boston Scientific, developed the WATCHMAN device, a small mesh umbrella that can be inserted into part of the heart cavity to prevent the formation of blood clots that cause strokes.

Currently, the anti-coagulant drug warfarin is used to prevent strokes, but the drug comes with other risks.

"Warfarin has a lot of side-effects. One major side-effect is the bleeding risk," said paper author Dr. Sven Mobius-Winkler. "Therefore, only 50 percent of the patients who should take Warfarin actually take it."

The WATCHMAN device gives patients another option. It has already been approved for use in the European Union and Australia, and secured investigational approval from the FDA in 2009.

To help train doctors how to use the device, doctors from the University of Leipzig Heart Center in Germany are publishing the full WATCHMAN placement procedure in the Journal of Visualized Experiments (JoVE), the world's first and only peer-reviewed, PubMed indexed, science and medicine video journal.

"Intervention and closure of the left atrial appendage is a complex procedure," said Dr. Mobius- Winkler. "For inexperienced physicians, it is hard to learn this procedure and therefore the video can help by doing step-by-step the implantation."

"The WATCHMAN device will give patients with atrial fibrillation another option rather than anti-coagulant drugs," said JoVE Editor Dr. Robert Dolan. "This article demonstrates the implantation of the device and will help clinicians gain expertise with the procedure, helping many of the patients who are unable or unwilling to take warfarin."