Provides new standard of care for preventing recurrent strokes in this patient population
A new classification system, developed by researchers at the Predictive Analytics and Comparative Effectiveness (PACE) Center at Tufts Medical Center and their collaborators, can assess with high accuracy whether patients with ischemic stroke of unknown origin would benefit from a procedure to close the patent foramen ovale (PFO). The results of the study, “Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data from Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke,” were published in the December, 2021 issue of The Journal of the American Medical Association (JAMA).
The PFO is a small hole in the heart wall between the right and left atria. Every person is born with a PFO, but for most people, the hole closes on its own shortly after birth. However, in about 20-25 percent of the population, the PFO never closes. This may allow a blood clot to travel through the hole, up to the brain, and cause a stroke. While most people have no symptoms and live their whole lives without ever knowing they have a PFO, approximately 10 percent of strokes in people ages 18-60 have been PFO-associated and approximately 40-50 percent of patients with strokes of unknown origin have been found to have a PFO.
“While PFO closure has been found to reduce the overall risk of recurrent stroke, it had previously been unclear whether this approach would be beneficial for every individual stroke patient, or if other therapies might be more appropriate in certain cases,” said study first author David Kent, MD, Director of the PACE Center at Tufts Medical Center. “Our classification system can help predict with great precision which of these patients would benefit from PFO closure and which might be effectively treated with medical therapy alone.”
The study examined individual patient data from 3,740 patients who participated in six randomized clinical trials comparing PFO closure plus medical therapy with just medical therapy alone, in patients with PFO-associated stroke. The study authors then used each patient’s Risk of Paradoxical Embolism (RoPE) Score (a classification system developed by the same Tufts MC team in 2013, in which different “points” are assigned for several criteria, including age, history of hypertension and diabetes and smoking history) and combined this with physiological PFO attributes of each patient to create a new system--the PASCAL Classification System—which classifies each patient as “likely,” “possible” or “unlikely” that a PFO was a direct cause of their stroke. Using the final classification system, the researchers found that patients for whom the formula recommended PFO closure received a 90 percent risk reduction in recurrent stroke, while those in the “unlikely” category did not benefit at all. Moreover, patients in the “unlikely” category were at a substantially higher risk of suffering adverse events from PFO closure.
“This classification system is much more reliable than any previous model in determining which patients are most likely to benefit from having their PFO closed,” said Dr. Kent. “We believe this formula will translate to clinically meaningful changes to help reduce recurrent strokes, prevent unnecessary procedures and change practice for this patient population. The dramatic results we see in this project should encourage other researchers to apply multivariable predictive methods for identifying subgroups to provide better personalized evidence from clinical trials.”
“The findings of this study by Kent et al provide critical evidence that can immediately influence the clinical evaluation and care of patients with cryptogenic stroke and PFO,” wrote Robert W. Yeh, MD, from Beth Israel Deaconess Medical Center and Doreen DeFaria Yeh, MD, from Massachusetts General Hospital, in an accompanying editorial. “Rigorous analysis of individual patient data from 6 well-conducted randomized clinical trials meets the standard of being among the highest levels of evidence to date.”
The project was supported by a grant to the PACE Center from the Patient Centered Outcome Research Institute (PCORI) and was part of a larger, first-of-its-kind national award to develop methods to better individualize the results from randomized clinical trials.
