Correspondence

In Reply

Dtsch Arztebl Int 2018; 115: 56-7. DOI: 10.3238/arztebl.2018.0057
Juvenile Stroke—A Practice-Oriented Overview by Dr. med. Florian Schöberl, Prof. Dr. med. Peter Arthur Ringleb, PD Dr. med. Reza Wakili, Dr. med. Sven Poli, PD Dr. med. Frank Arne Wollenweber, and PD Dr. med. Lars Kellert in issue 31–32/2017

Kellert, L; Schöberl, F

LNSLNS

We refer to Professor Stang’s critical comments in response to our article on the therapeutic effect of interventional PFO closure on the risk of recurring stroke.

As explained by Stang, in order to interpret the NNT of interventional PFO closure in a useful way, the comparators (that is, alternative treatments) and the follow-up period are crucial.

As Stang correctly reported, the follow-up period in the meta-analysis we cited in our article was 2.5 years (1, 2). Regarding the varying comparators from the three studies pooled in this meta-analysis (CLOSURE I, RESPECT, and PC), Stang’s comment is not entirely correct: the alternative treatments in the control arms were not merely platelet aggregation inhibitors alone, as well as a combination of platelet aggregation inhibitors plus oral anticoagulation with a vitamin K antagonist (warfarin), but also warfarin treatment alone (1). Medication treatment using different platelet aggregation inhibitors was also given to the PFO closure groups (1).

Stang explains the term NNT by using as an example the meta-analysis by Kent et al., which we cited in our article (1): if 67 patients are treated with PFO closure and 67 patients are treated with the comparator treatment, one additional ischemic stroke can be expected to be prevented over 2.5 years of follow-up. He is therefore correct in his criticism that the formulation we used—“to prevent another stroke” is incorrect—it should have said “to prevent one additional stroke.”

We agree with Lange, that in view of the latest evidence from studies, PFO closure should undergo re-assessment. The studies cited by Dr Lange—REDUCE and CLOSE—were published in the New England Journal of Medicine on 14 September 2017; we were therefore unable to consider them in our review article on juvenile stroke (3, 4). Our article refers to the guidelines that are currently still valid. Whether and to what extent the guidelines will change as a result of these recent studies remains to be seen. Regarding content, we take the view that even in future, the indication for PFO closure will remain an individual decision. In brief, the recently published studies lead us to conclude that a selected group of patients (age <60 years, PFO with atrial septal aneurysm and/or large interatrial shunt, no rival cause of stroke except for the PFO) will benefit from PFO closure compared with platelet aggregation inhibitor treatment alone, as regards preventing recurring stroke. However, insufficient data exist regarding a comparison group receiving oral anticoagulants. A point of criticism is also the increased rate of atrial fibrillation in the intervention group. It is completely unclear what the implications of this will be, especially in view of the absence of long-term data.

DOI: 10.3238/arztebl.2018.0057

On behalf of the authors

PD Dr. med. Lars Kellert

Neurologische Klinik und Poliklinik

Klinikum der Universität München

Lars.Kellert@med.uni-muenchen.de

Dr. med. Florian Schöberl

Conflict of interest statement

PD Dr. Kellert has received consultant fees from Bayer, Boehringer Ingelheim, and Daiichi Sankyo; travel expenses and congress participation fee reimbursement from Bayer, Daiichi Sankyo, and Pfizer; and speaking honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer.

Dr. Schöberl declares that no conflict of interest exists.

1.
Kent DM, Dahabreh IJ, Ruthazer R, et al.: Device closure of patent foramen ovale after stroke: pooled analysis of completed randomized trials. J Am Coll Cardiol 2016; 67: 907–17 CrossRef MEDLINE PubMed Central
2.
Schöberl F, Ringleb PA, Wakili R, Poli S, Wollenweber FA, Kellert L: Juvenile stroke—a practice-oriented overview. Dtsch Arztebl Int 2017; 114: 527–34 VOLLTEXT
3.
Mas JL, Derumeaux G, Guillon B, et al.: Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 2017; 377: 1011–21 CrossRef MEDLINE
4.
Søndergaard L, Kasner SE, Rhodes JF, et al.: Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 2017; 377: 1033–42 CrossRef MEDLINE
1.Kent DM, Dahabreh IJ, Ruthazer R, et al.: Device closure of patent foramen ovale after stroke: pooled analysis of completed randomized trials. J Am Coll Cardiol 2016; 67: 907–17 CrossRef MEDLINE PubMed Central
2.Schöberl F, Ringleb PA, Wakili R, Poli S, Wollenweber FA, Kellert L: Juvenile stroke—a practice-oriented overview. Dtsch Arztebl Int 2017; 114: 527–34 VOLLTEXT
3. Mas JL, Derumeaux G, Guillon B, et al.: Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 2017; 377: 1011–21 CrossRef MEDLINE
4.Søndergaard L, Kasner SE, Rhodes JF, et al.: Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 2017; 377: 1033–42 CrossRef MEDLINE

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