WATCHMAN: will it replace warfarin in some patients? (updated) 2

Updated with commentary from David Kandzari– The WATCHMAN percutaneous left atrial apendage closure device is as effective as warfarin in reducing the risk of stroke in patients with non-valvular AF, but use of warfarin is not likely to go away anytime soon, according to the publication of the PROTECT AF trial in the Lancet and an accompanying comment.

Results of PROTECT AF were initially presented in March at the ACC and the device received a cautious approval recommendation from an FDA advisory panel a month later.

The authors conclude: “The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety events in the intervention group than the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.”

However, “warfarin is still the treatment of choice in patients with non-valvular atrial fibrillation who have clear indications for, and who are suitable for treatment with, long-term oral anticoagulation,” write Dominick McCabe, Justin Kinsella, and W Oliver Tobin, in an accompanying comment. Although the device may be particularly helpful in patients in whom anticoagulation therapy is contraindicated, they note that “the trial did not include any patients deemed unsuitable for long-term warfarin, a population in which this device might be particularly suited, but for which we have no evidence at present.”

Update: David Kandzari sent the following comment to CardioBrief:

I am very optimistic for LAA closure, but I think there are a number
of challenges ahead for formal device approval and adoption. First,
among investigators in the field of AF and the clinical community, we
are accustomed to trials involving patient populations on the order of
thousands rather than 900. The sophisticated Bayesian analysis that
resulted in non-inferiority may be a very efficient method for
clinical trial performance, but I think it is difficult for practicing
clinicians to interpret and instead their use may be based more on
intuiton of the device’s benefits rather than the trial results per
se. Second, the trial was studied in patients who were eligible for
warfarin anticoagulation, but it is clearly intended for those who are
not perceived candidates for warfarin therapy. I think it’s an
interesting dilemma that the device, if approved, would be principally
directed from the outset for ‘off-label’ use, ie, in a population in
whom the device was not specifically studied. Also, I believe the
complication rate, which reportedly declined with device revision and
operator experience, represents two dilemmas, one on the clinical
front, the second on the regulatory front– who will be performing
these procedures (expectedly, skilled operators at limited centers)?
And, what type of post market surveillance requirements must be
established to reassure the device’s safety in ‘real world’ practice?
Finally, as before, I am very encouraged by this technology, but like
percutaneous valve therapies, we need to remind ourselves that this is
a first generation device, and there are likely iterative improvements
that will make this a safer and possibly even more effective
technology.

Here is the Lancet press release:

DEVICE ALTERNATIVE TO LONG TERM WARFARIN THERAPY COULD BE AN OPTION FOR PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION AT RISK OF STROKE

Patients with atrial fibrillation at risk of stroke could be offered percutaneous closure of the left atrial appendage instead of long-term warfarin therapy. The findings, from the PROTECT AF study, are reported in an Article in this week’s edition of The Lancet, written by Professor David R Holmes, Mayo Clinic, Rochester, MN, USA, and colleagues.

Atrial fibrillation is the most common sustained cardiac arrhythmia (irregular heartbeat), and its prevalence is expected to increase as the world’s populationages. Atrial fibrillation causes the upper chambers of the heart to quiver, this can cause blood to pool and form blood clots in an area of the heart called the left atrial appendage (LAA).  The LAA, an embryonic remnant of the original left atrium, is a long, tubular structure that is connected to  the left atrial cavity. More than 90% of atrial thrombi in patients with non-valvular atrial fibrillation are believed to originate in the LAA. In this randomised study, the authors assessed the efficacy and safety of percutaneous closure of the LAA compared with long term warfarin therapy in patients with non-valvular atrial fibrillation at risk for stroke.

Patients were eligible for the study if they had at least one of the following: previous stroke or transient ischaemic attack*, congestive heart failure, diabetes, high blood pressure, or were 75 years or older. A total of 707 patients were randomised in a 2:1 ratio to percutaneous closure of the LAA and subsequent discontinuation of warfarin (463 patients) or to long term warfarin therapy (244 patients). The percutaneous procedure involved implantation of a device (the WATCHMAN) to close off the LAA. Efficacy was assessed through a combined endpoint of all stroke (ischeamic and haemorrhagic), cardiovascular death, and systemic embolism (a blood clot that goes somewhere other than the brain). Serious adverse events that were part of the safety assessment included major bleeding, pericardial effusion (an accidental puncture of the heart causing fluid collection in the heart sac), and device embolisation.

The authors found that after 1065 patient years of follow up, there were 3.0 efficacy events per 100 patient-years in the device group, compared with 4.9 in the warfarin group—a relative reduction of 38%. However, serious safety events were more common in the device group (7.4 events per 100 patient-years) compared with the warfarin group (4.4); most of these safety events were related to the procedural implant.

The authors conclude: “The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety events in the intervention group than the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.”

In an accompanying Comment, Drs Dominick J H McCabe, Justin A Kinsella, and W Oliver Tobin, Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital, Trinity College, Dublin, Ireland, say that despite its limitations, warfarin is still the treatment of choice for patients with non-valvular atrial fibrillation who have clear indications for, and who are suitable for long-term oral anticoagulation. However they add that further research is warranted into the use of left atrial appendage occlusion devices, particularly for patients unsuitable for long term warfarin therapy.

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2 comments

  1. Pingback: FDA: Watchman device will need to wait a bit longer « CardioBrief

  2. Pingback: Late-Breaking News: Confusion Over ACC Late-Breaker Trial « CardioBrief

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