Sohei Yoshimura, MD, PhD

Kent DM, Saver JL, Ruthazer R, Furlan AJ, Reisman M, Carroll JD, Smalling RW, Jüni P, Mattle HP, Meier B, et al. Risk of Paradoxical Embolism (RoPE)-Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure: An Analysis of 3 Trials. Stroke. 2020;51:3119–3123.

The Risk of Paradoxical Embolism (RoPE) score was developed to predict the probability of patent foramen ovale (PFO) presence in a patient with cryptogenic stroke (CS), and is also known as a score useful to predict the probability that a documented PFO is causally related to the stroke, rather than an incidental finding. The latter significance of the RoPE score is proposed by calculating the RoPE-estimated attributable fraction according to the Bayes theorem. The 10-point RoPE score is calculated based on age, the presence of a cortical stroke on neuroimaging, and the absence of the following factors: diabetes, hypertension, smoking, and prior stroke or transient ischemic attack (TIA). The group of CS patients with high RoPE score was reported to have high RoPE-estimated attributable fraction and, interestingly, low estimated stroke recurrence rate.

The objective of this research was to examine the treatment effect of PFO closure across the level of RoPE score. The study included pooled individual data from 3 randomized trials: the CLOSURE-I, RESPECT, and PC trial. In the low RoPE score group (<7, n=912), there was no significant difference in the rate of recurrent strokes per 100 person-years between the PFO closure arm and the medical arm (1.37 vs 1.68; hazard ratio, 0.82 [0.42–1.59] P=0.56). On the other hand, risk of recurrent stroke reduced significantly by PFO closure (0.30 vs 1.03; hazard ratio, 0.31 [0.11–0.85] P=0.02) in the high RoPE score group (≥7, n=1221). Pearson correlation showed strong association between the RoPE-estimated attributable fraction and the relative risk reduction of PFO closure .

Meta-analyses of randomized trials showed that PFO closure for CS patients aged <60 years conferred a reduction in ischemic stroke recurrence compared to antiplatelet therapy, and probably had a lower risk of major bleeding compared to anticoagulation. However, PFO closure incurred a risk of persistent atrial fibrillation (AF). Because each of these trials had restrictive eligibility criteria, current evidence on cost-effectiveness is insufficient to justify widespread use of PFO closure in all CS patients with PFO. The RoPE score, an index composed of basic history and neuroimaging data, could maximize the benefit of PFO closure by selecting those patients predicted to have a higher relative risk reduction of recurrent stroke. 

PFO closure might be more effective in specific groups of patients according to PFO characteristics including those with large shunts, atrial septal aneurysm, Eustachian valve, Chiari network, and long tunnel PFOs. Additional studies considering these anatomical features could improve estimation of attributable fraction by the Bayes theorem. Evaluating net clinical benefit considering not only ischemic stroke recurrence, but also major bleeding, AF burden and quality-adjusted life year (QALY) may also be important.