Journal of Neurology (2018) 265:1259–1268
Closure of patent foramen ovale for cryptogenic stroke patients:
an updated systematic review and meta‑analysis of randomized trials
· Guang Ou‑Yang
· Peng‑fei Yan
· Shu‑lan Huang
· Zhen‑tao Zhang
· Zhao‑hui Zhang
Received: 23 December 2017 / Revised: 21 January 2018 / Accepted: 23 January 2018 / Published online: 30 January 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Objective This systematic review and meta-analysis was performed to investigate the eﬃcacy and safety of transcatheter
device closure (TDC) plus anti-thrombotic drugs over medical management alone for patients with cryptogenic stroke and
patent foramen oval.
Methods PubMed, Embase and Cochrane Library database were searched for randomized controlled clinical trials (RCTs).
The primary endpoint is the composite of stroke and transient ischemic attack. The secondary endpoints are all-cause mor-
tality, total serious adverse events, atrial ﬁbrillation and bleeding.
Results Five RCTs with a total of 3440 participants were included. TDC signiﬁcantly decreased the risk of primary endpoint
when compared to medical therapy alone (RR 0.54, 95% CI 0.43–0.69). Further subgroup analyses showed that patients
with male gender and with substantial shunt size of foramen ovale signiﬁcantly beneﬁted from TDC as compared to those
with female gender and with no substantial shunt size of foramen oval separately. Moreover, TDC was superior to medical
therapy with anti-platelet drug alone (not with anti-coagulation). On the other hand, the incidence of atrial ﬁbrillation was
higher in TDC group (RR 4.49, 95% CI 2.02–9.97), with the risk of other adverse events equivalent between the two groups.
Conclusions TDC plus anti-thrombotic drugs is superior than medical therapy alone for secondary prevention of stroke,
especially for those with male gender and with substantial shunt size of foramen ovale. Though it may increase the risk of
postoperative atrial ﬁbrillation, it would not bring higher risk of all-cause mortality, total adverse events and bleeding.
Keywords Meta-analysis · Cryptogenic stroke · Patent foramen ovale · Closure
Stroke is the second most common cause of death and the
leading cause of disability worldwide , of which ischemic
stroke accounts for about 80% . Atherosclerosis, arteri-
tis, heart disease, and the change of blood component or
hemodynamics are common causes of ischemic stroke [3,
4]. However, the reason for about one-third of adult ischemic
stroke cannot be defined, which is called cryptogenic
stroke . Numerous studies have shown a close relation-
ship between patent foramen ovale (PFO) and cryptogenic
stroke [6, 7]. The incidence of PFO ranges from 20 to 26%
in the general population , and it may be as high as 56%
in patients younger than 55 years of age with cryptogenic
stroke [7, 9, 10]. Paradoxical embolism is the possible mech-
anism of ischemic stroke induced by PFO, which refers to
the embolism from the vein system or right atrium through
the right to left shunt into the arterial system [4, 11].
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s0041 5-018-8766-2) contains
supplementary material, which is available to authorized users.
Xuan Niu and Guang Ou-Yang contributed equally to this article.
* Zhao-hui Zhang
Department of Neurology, Renmin Hospital of Wuhan
University, Wuhan 430060, China
Department of Neurosurgery, Renmin Hospital of Wuhan
University, Wuhan 430060, China
Department of Neurosurgery, Union Hospital, Tongji
Medical College, Huazhong University of Science
and Technology, Wuhan 430022, China