A higher rate of adverse events in the angioplasty/stenting arm of the randomized SAMMPRIS trial forced an early halt to the stroke prevention study, according to trial sponsor, the National Institute of Neurological Diseases and Stroke.
With just over half of the planned number of patients enrolled, 14% of those who underwent angioplasty had suffered a stroke or died within the first 30 days, compared with 5.8% of those treated with aggressive medical therapy alone, the NINDS said in a statement.
"The SAMMPRIS Executive Committee is in agreement with NINDS and the data safety and monitoring board that enrollment in the study should be stopped and that the trial data currently available indicate that aggressive medical management alone is superior to angioplasty combined with stenting in patients with recent symptoms and high grade intracranial arterial stenosis," the statement said.
The difference in event rates was "highly significant," according to the statement, which pointed out another surprise: The event rate in the medical-therapy arm was about half what has been observed in earlier studies.
According to NINDS, in historical controls the rate of strokes or death with aggressive medical therapy was 10.7%.
SAMMPRIS -- an acronym for Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis -- began enrolling patients in November 2008. It was halted last week after an interim review by the data safety and monitoring board.
A total of 451 of the planned 764 patients had been treated in the study, the first randomized trial to compare aggressive medical therapy alone with angioplasty and stenting plus aggressive medical management.
The medical therapy in both arms included aspirin at 325 mg/day for the entire follow-up; clopidogrel (Plavix) at 75mg/day for 90 days after enrollment; intensive management of vascular risk factors, including a systolic blood pressure target of less than 140 mm Hg and LDL cholesterol less than 70 mg/dL; and a lifestyle modification program.
The angioplasty arm used the Gateway-Wingspan system, according to NINDS.
Stroke physicians contacted by MedPage Today and ABC News expressed disappointment that the angioplasty-based treatment apparently failed so dismally.
"Obviously, this is not what the investigators or the stroke community at large was hoping for because medical management of this condition has not been very effective in the past," said Stanley Tuhrim, MD, of Mount Sinai Stroke Center in New York City, in an email.
Pierre Fayad, MD, of the University of Nebraska in Omaha, sounded a similar note. "This is, of course, a major disappointment for a novel treatment to improve the care of patients at risk for stroke with narrowing in the brain blood vessels inside the skull," he said in an email.
"At the same time, it is a relief and reassurance that with good medical treatment alone, patients with such disease can do okay," he added.
Joe Broderick, MD, of the University of Cincinnati, suggested that the findings "will change practice."
In an email, Broderick said the truncated trial had two important messages. One was that better outcomes in the control arm "likely reflects that aggressive medical therapy of current standards is an improvement over the past," he wrote.
The other, he said, was that the event rate with stenting was higher than previously reported in registries -- "not surprising [because] registries don't have the rigor of clinical trials."
"These two factors will result in intracranial stenting being used in very, very limited settings (patients with high grade stenoses who literally cannot sit up without becoming symptomatic and who have failed medical therapy)," Broderick wrote.
But Tuhrim suggested that the SAMMPRIS results may not tell the whole story. He pointed out that patients on medical therapy tend "to fall off the wagon over time," in which case the benefit would not be sustained.
"Stents, on the other hand, seem to be durable (and the argument [is] that the stents and the operators will get better over time), at least so far," Tuhrim wrote in the email.
"It remains an open question whether a study of longer duration would produce similar results or if a turning point would be reached down the road." more read...
With just over half of the planned number of patients enrolled, 14% of those who underwent angioplasty had suffered a stroke or died within the first 30 days, compared with 5.8% of those treated with aggressive medical therapy alone, the NINDS said in a statement.
"The SAMMPRIS Executive Committee is in agreement with NINDS and the data safety and monitoring board that enrollment in the study should be stopped and that the trial data currently available indicate that aggressive medical management alone is superior to angioplasty combined with stenting in patients with recent symptoms and high grade intracranial arterial stenosis," the statement said.
The difference in event rates was "highly significant," according to the statement, which pointed out another surprise: The event rate in the medical-therapy arm was about half what has been observed in earlier studies.
According to NINDS, in historical controls the rate of strokes or death with aggressive medical therapy was 10.7%.
SAMMPRIS -- an acronym for Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis -- began enrolling patients in November 2008. It was halted last week after an interim review by the data safety and monitoring board.
A total of 451 of the planned 764 patients had been treated in the study, the first randomized trial to compare aggressive medical therapy alone with angioplasty and stenting plus aggressive medical management.
The medical therapy in both arms included aspirin at 325 mg/day for the entire follow-up; clopidogrel (Plavix) at 75mg/day for 90 days after enrollment; intensive management of vascular risk factors, including a systolic blood pressure target of less than 140 mm Hg and LDL cholesterol less than 70 mg/dL; and a lifestyle modification program.
The angioplasty arm used the Gateway-Wingspan system, according to NINDS.
Stroke physicians contacted by MedPage Today and ABC News expressed disappointment that the angioplasty-based treatment apparently failed so dismally.
"Obviously, this is not what the investigators or the stroke community at large was hoping for because medical management of this condition has not been very effective in the past," said Stanley Tuhrim, MD, of Mount Sinai Stroke Center in New York City, in an email.
Pierre Fayad, MD, of the University of Nebraska in Omaha, sounded a similar note. "This is, of course, a major disappointment for a novel treatment to improve the care of patients at risk for stroke with narrowing in the brain blood vessels inside the skull," he said in an email.
"At the same time, it is a relief and reassurance that with good medical treatment alone, patients with such disease can do okay," he added.
Joe Broderick, MD, of the University of Cincinnati, suggested that the findings "will change practice."
In an email, Broderick said the truncated trial had two important messages. One was that better outcomes in the control arm "likely reflects that aggressive medical therapy of current standards is an improvement over the past," he wrote.
The other, he said, was that the event rate with stenting was higher than previously reported in registries -- "not surprising [because] registries don't have the rigor of clinical trials."
"These two factors will result in intracranial stenting being used in very, very limited settings (patients with high grade stenoses who literally cannot sit up without becoming symptomatic and who have failed medical therapy)," Broderick wrote.
But Tuhrim suggested that the SAMMPRIS results may not tell the whole story. He pointed out that patients on medical therapy tend "to fall off the wagon over time," in which case the benefit would not be sustained.
"Stents, on the other hand, seem to be durable (and the argument [is] that the stents and the operators will get better over time), at least so far," Tuhrim wrote in the email.
"It remains an open question whether a study of longer duration would produce similar results or if a turning point would be reached down the road." more read...
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