Patent foramen ovale and the risk of cryptogenic stroke.

COMMENTARY JONATHAN TOBIS. MD* Clinical Professor of Medicine, Director of In- terventional Cardiology Research, and Director, Interventional Cardiology Fellowship Program, University of California, Los Angeles Patent foramen ovale and the risk of cryptogenic stroke HE ARTICLE BY ROTH AND ALL1 in this issue describes Tin depth more than 10 years of research that address— es the question, Should we close a patent foramen ovale (PFO) to prevent recurrent cryptogenic stroke? See related article, page 417 There is no longer any doubt that PFO can be the pathway for thrombus from the venous circulation to go from the right atrium to the left atrium, bypassing the pulmonary capillary ﬁltration bed, and entering the arterial side to produce a stroke, myocardial in— farction, or peripheral embolus. Two questions remain: What should we do to prevent another episode? And is percutaneous closure of a PFO with the current de- vices preferable to medical therapy? How much do we know about the risks and beneﬁts of closure of PFO? I maintain that we know a great deal about interatrial shunt and paradoxical embolism as a cause of cryptogenic stroke. Prospective random- ized clinical trials now give us data with which we can provide appropriate direction to our patients. Percu— taneous closure is no longer an “experimental proce- dure,” as insurance companies claim. The experiment has been done, and the only issue is how one inter- prets the data from the randomized clinical trials. The review by Roth and Alli comprehensively de— scribes the observational studies, as well as the three randomized clinical trials done to determine whether PFO closure is preferable to medical therapy to pre— vent recurrent stroke in patients who have already had one cryptogenic stroke. If we understand some of the subtleties and differences between the trials, we can reach an appropriate conclusion as to what to recom— mend to our patients. *Dr. Tobis is one of the principal investigators of the PREMIUM Trial, which is assessing the benefit and safety of the Amplatzer PFO closure device to treat patients with debilitat- ing migraine headache. doi:1 0.3949/ccjm.8&#39;| a.1 4066 CLEVELAND CLINIC JOURNAL OF MEDICINE A review of 10 reports of transcatheter closure of PFC vs six reports of medical therapy for cryptogenic stroke showed a range of rates of recurrent stroke at 1 year—between 0% and 4.9% for transcatheter clo— sure, and between 3.8% and 12% for medical therapy.1 These numbers are important because they were used to estimate the number of patients that would be necessary to study in a randomized clinical trial to demonstrate a benefit of PFC closure vs medical therapy. Unlike most studies of new devices, the PFC closure trials were done in an environment in which patients could get their PFO closed with other devices that were already approved by the US Food and Drug Administration (FDA) for closure of an atrial septal defect. This ability of patients to obtain PFO closure outside of the trial with an off—label device meant that the patients who agreed to be randomized tended to have lower risk for recurrence than patients studied in the observational populations. From a practical standpoint, this meant that the event rate in the pa- tients who participated in the randomized clinical tri~ als (1.7% per year) was lower than predicted from the observational studies.“ Another way of saying this is that the randomized clinical trials were underpowered to answer the ques— tion. A common way of dealing with this problem is to combine the results of different studies in a meta— analysis. This makes sense if the studies are assessing the same thing. This is not the case with the PFO clo— sure trials. Although the topic of percutaneous PFO closure vs medical therapy was the same, the devices used were different. In the CLOSURE trial (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient lschemic Attack Due to Pre- sumed Paradoxical Embolism Through a Patent Fo- ramen Ovale),3 the device used was the STARFlex, which is no longer produced—and for good reasons. It is not as effective as the Amplatzer or Helex devices in VOLUME 81 0 NUMBER 7 JULY 2014