AMPLATZER™ PFO Occluder courtesy St. Jude Medical
DENVER – Young stroke survivors know the risk and fear of suffering a second stroke. A new study out today suggests that in carefully selected patients, a non-surgical approach may be part of a comprehensive strategy to take away some of that fear. The clinical trial RESPECT study was published in the New England Journal of Medicine and was first authored by John D. Carroll, MD, University of Colorado Professor of Medicine and Director of Interventional Cardiology at the University of Colorado Hospital.
According to the World Health Organization (WHO), an estimated 15 million people worldwide suffer from stroke each year. It is estimated that 87 percent of all strokes are ischemic strokes, which occur when blood clots block the blood vessels to the brain. Up to 40 percent of ischemic strokes are classified as cryptogenic, which means the cause of the stroke is unknown.
For more than 15 years, it has been recognized that 50-60 percent of people having a cryptogenic stroke also have a patent foramen ovale (PFO), a flap between the two upper chambers of the heart that is present in everyone when they are in utero and persists into adulthood in 25 percent of the general population, usually causing no health problems. But in some cases, a blood clot can cross the PFO and enter the brain, causing a stroke. Researchers in this trial looked at whether closing the PFO with a small medical device that acts like a paperclip reduced the risk of a second stroke.
The RESPECT trial (Randomized Evaluation of recurrent Stroke comparing PFO closure to Established Current standard of care Treatment) is in important next step in helping provide new avenues of care of patients. This publication is the first comprehensive report from this trial and the patients continue to be monitored and additional data will be reported. Doctors in this national trial conducted at 69 centers in the United States and Canada inserted a small mesh device into the heart to close the PFO. Patients participating in the trial were randomized to either receiving the device with medications or medications alone. The medical therapy group could receive four different medicines including aspirin, warfarin, clopidogrel and aspirin combined with extended-release dipyridamole; and the device group was treated with the Amplatzer PFO Occluder, made by St. Jude Medical. Some of the many questions asked included which group had fewer second strokes, how safe was the procedure and the device, and were the recurrent strokes those from other causes?
“The reassuring news is that that rate of recurrent strokes was low for both groups. The exciting news is that there was a strong suggestion that the addition of the PFO closure to a strategy to reduce stroke risk may reduce the risk further than medications alone: the risk at five years was 2.2 percent of those receiving the device versus 6.4 percent receiving medications alone,” said Carroll. He cautioned that the results of RESPECT cannot be considered 100 percent, definitive but clearly advances the fund of knowledge in the field.
“Clinical trials advance medical knowledge step-by-step over years. They answer some questions and they bring up new question. Clinical trials use statistical tests to assess whether the results have a low chance of being due to chance as assessed by the P value. We performed three statistical tests for the superiority of device therapy and the primary test gave a p=0.08 which is less than the p<0.05 we use for calling the results definitive. Two other tests gave P values less than 0.05. The scientific discussion and debate of these results starts after the publication and also will take place at a device regulatory level controlled by the Food and Drug Administration (FDA),” said Carroll.
The medical device used in RESPECT is investigative in the United States. The FDA has the responsibility of deciding if the device should be approved for commercial sale and for what indication. Carroll called the study a unique “landmark trial” looking to find answers to an important clinical question requiring two medical disciplines to partner in designing and executing the trial over an eight year period. The work brought together cardiologists and neurologists to evaluate and treat the patients who consented to being in the trial after their initial stroke.
In the published paper entitled “Transcatheter PFO Closure versus Medical Therapy after Cryptogenic Stroke”, the safety of the procedure, device, and medications are also reported. There was a low frequency of serious complications during the procedure, no deaths related to the treatments studied, and a rate of serious adverse events that was similar in the two arms of the study.
University of Colorado Hospital enrolled 33 patients in the trial.