Long-Term Consequences Post Device Closure of Patent Foramen Ovale in Patients With Cryptogenic Embolism

Recently, Jérôme Wintzer-Wehekind M.D. and his team at Quebec Heart & Lung Institute, Laval University, Quebec, Canada conducted a vast cohort study published in the Journal of American College of Cardiology to look into the long-term outcomes (> 10 years) following PFO closure. Previous randomized trials conducted by various investigators had shown a marvelous reduction in ischemic stroke events for around 2-6 years post PFO closure but not many had gone beyond 10 years. The current study validated that device closure of PFO decreased recurrence of ischemic neurological events and continued to show similar results with the passage of time. A cohort of 201 consecutive patients, who underwent PFO closure between 2001 and 2008 was selected and data related to ischemic and bleeding events and antithrombotic medication was collected for 10 to 17 years. An impressive 96% of patients had completed this follow-up. Patent foramen ovale (PFO) closure was recently accepted as the gold standard for treating patients with cryptogenic stroke as a secondary preventive intervention in patients with an increased risk of paradoxical emboli after an ischemic event, not in otherwise healthy patients.

Overall, the findings showed that a total of 13(0.6% per year) patients died from non-cardiovascular causes, 2 patients (0.1% per year) had a non-disabling stroke, and TIA occurred in 6 patients (0.3% per year). Comparatively more hemorrhagic events were observed than ischemic events. Major bleeds occurred in 2% (0.2%per year) of the patients, all of whom were on antithrombotic therapy at the time of the event. A higher rate of ischemic events was noticed in patients with thrombophilia, including 15% of the patients. Anti-thrombotics were discontinued in one-fifth of the patients during the follow-up period, mostly within the first year post-PFO closure and this was not associated with an increase in ischemic events at long-term follow-up. Interestingly, all ischemic neurological recurrences were seen in patients treated with either aspirin or clopidogrel. The investigators believed that the use of antithrombotics in these patients especially in the younger generation was uncertain pertaining to the lack of risk factors such as hypertension and tobacco use. For the first time though, this study found that the use of aspirin once PFO closure was done could lead to troublesome bleeds.

Senior author Dr. Josep Rodés-Cabau, M.D. stated that, “Limited data exist on long-term outcomes following PFO closure; it would, therefore, be important to obtain much longer-term follow-up data among PFO closure recipients to determine recurrent ischemic events as well as the occurrence of concomitant events such as atrial fibrillation or venous thrombosis at long-term follow-up. Also, long-term antiplatelet therapy is currently recommended in such patients (as for any patient diagnosed with ischemic stroke), but the optimal duration of anti-thrombotic therapy following PFO closure has not yet been evaluated.” Thus, Dr. Winter-Wehekind and his team implored the productiveness of continued anti-thrombotic therapy post-PFO closure and said that the use of these drugs for a shorter duration (<12  months) could be a safe option and must be explored in future studies.  The discontinuation of anti-thrombotic after a short duration though is debatable as most neurologists still continue to use it as a treatment module in patients with ischemic events, as the presence of venous thrombosis is many times obligatory for PFO-derived stroke. Nevertheless, the investigators believed that even though a few patients were lost during follow- up, their study could be limited by the probability of a few unaccounted adverse effects. The study primarily furthered the follow-up of recent randomized PFO trials like CLOSE, DEFENSE-PFO, REDUCE, and RESPECT reflecting their findings by demonstrating a low stroke rate (0.08 per 100 patient-years).  Therefore, the study supported the fact that the inceptive benefits observed with PFO closure with reference to medical treatment were preserved at long-term follow-up.