An Alternative to Long-Term Warfarin Therapy for Preventing Stroke?
The efficacy of percutaneous closure of the left atrial appendage is noninferior to warfarin therapy, and may be an alternative strategy for stroke prophylaxis in patients with nonvalvular atrial fibrillation, according to a study in the August 15 Lancet.
In the multicenter, randomized PROTECT AF study, David R. Holmes, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues included 707 adult patients with nonvalvular atrial fibrillation. In addition, all subjects had at least one of the following—previous stroke or transient ischemic attack, congestive heart failure, diabetes, or hypertension, or were ages 75 and older. Participants were randomized to percutaneous closure of the left atrial appendage and subsequent discontinuation of warfarin (intervention, n = 463) or warfarin treatment with a target international normalized ratio between 2.0 and 3.0 (control, n = 244).
The WATCHMAN device (Atritech, Plymouth, Minnesota) was successfully implanted in 88% of patients assigned to intervention and in 91% (408/449) of those in whom implantation was attempted. At the 45-day follow-up, 349 (86%) of 408 patients with an implanted device met transesophageal echocardiograph (TEE) criteria and were able to stop taking warfarin.
“The primary efficacy event rate was 3.0 per 100 patient-years in the intervention group and 4.9 per 100 patient-years in the control group (rate ratio, [RR] 0.62),” Dr. Holmes and coauthors stated. The cumulative rate for the intervention group was 5.9% at two years, compared with 8.3% for the control group.
“The primary efficacy event rate was 1.9 per 100 patient-years in successfully treated patients who discontinued warfarin in the intervention group compared with 4.6 per 100 patient-years in control patients who received warfarin (RR, 0.40),” Dr. Holmes and colleagues noted.
The rate of ischemic stroke was higher in the intervention group, while hemorrhagic strokes were more common in the controls. Primary safety events occurred at a higher rate in the intervention group (RR, 1.69). Twenty-two patients (4.8) who received intervention experienced serious pericardial effusion, the most frequent primary safety event in that group.
“Closure of the left atrial appendage might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation,” Dr. Holmes and coauthors concluded.
In a related comment, Dominick J. H. McCabe, MD, of Trinity College Dublin, and colleagues indicated that closure of the left atrial appendage is feasible, but associated with increased complications. “This population of patients must undergo longer-term clinical follow-up to assess the long-term efficacy and safety of having a WATCHMAN deployed in the left atrial appendage, and to inform future trials of such occlusion devices,” they stated.
Holmes DR, Reddy VY, Turi ZG. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomized non-inferiority trial. Lancet. 2009;374(9689):534-542.
McCabe DJ, Kinsella JA, Tobin WO. Left atrial appendage occlusion in non-valvular atrial fibrillation. Lancet. 2009;374(9689)504-506.
Unilateral Subthalamotomy Provides Motor Improvement in Patients With Parkinson’s Disease
Unilateral subthalamotomy is associated with significant and sustained motor benefit contralateral to the lesion in patients with Parkinson’s disease, according to a study in the September Journal of Neurology, Neurosurgery, and Psychiatry.
L. Alvarez, MD, of Centro Internacional de Restauración Neurológica in La Habana, Cuba, and colleagues observed 89 patients with Parkinson’s disease who were treated with unilateral subthalamotomy; 68 patients were evaluated after 12 months, 36 patients at 24 months, and 25 patients at 36 months.
“Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores improved significantly contralaterally to the lesion in the ‘off’ and ‘on’ states throughout the follow-up, except for the ‘on’ state at the last evaluation,” Dr. Alvarez and coauthors stated.
A significant reduction was seen in the “off” UPDRS-III at 12 months (50%), 24 months (30%), and 36 months (18%) postoperatively. Cardinal features (eg, bradykinesia, rigidity, and tremor) improved significantly contralateral to the lesion, and a mild and nonpersistent effect was observed ipsilaterally. At 36 months, UPDRS-III scores increased by 36.6% compared with the 12-month postoperative value, a difference due to higher scores at 36 months compared with 12 months (60 vs 38 points).
In the “on” motor state, UPDRS-III scores were significantly reduced at 12 and 24 months, postoperatively. “The improvement in ‘on’ was mainly due to a reduction in cardinal features in the contralateral side and axial signs,” the researchers noted. “Comparison of the UPDRS-III between 12 and 36 months showed significant difference, owing to higher scores at 36 months.” The deterioration at three years in the “on” score was associated with progressive worsening of the ipsilateral and axial features per the UPDRS-III.
“In conclusion, the results presented here confirm and expand previous reports indicating that unilateral subthalamotomy has a robust antiparkinsonian effect and may be performed with reasonable safety in Parkinson’s disease,” Dr. Alvarez and coauthors remarked.
“It should be noted that, based on limited data, unilateral subthalamotomy appears to be at least as effective as bilateral subthalamotomy, is associated with fewer adverse effects such as dysarthria and ataxia, but exerts less lasting ipsilateral improvement,” stated Daniel Tarsy, MD, Professor in Neurology at the Harvard Medical School in Boston, in a related editorial. “However, it is important for future studies in this area to include blinded clinical as well as postoperative brain imaging assessments to better correlate the size and precise location of subthalamic lesions with the therapeutic benefit and hemichorea-ballism which result.”
Alvarez L, Marcias R, Pavón N, et al. Therapeutic efficacy of unilateral subthalamotomy in Parkinson’s disease: results in 89 patients followed for up to 36 months. J Neurol Neurosurg Psychiatry. 2009;80(9):979-985.
Tarsy D. Does subthalamotomy have a place in the treatment of Parkinson’s disease? J Neurol Neurosurg Psychiatry. 2009;80(9):939-940.