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Effects of Phenobarbital and Levetiracetam on PR and QTc Intervals in Patients with Post-Stroke Seizure

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Abstract

Background and Objectives

Sudden unexplained/unexpected death (SUDEP) is related to high mortality in patients with epilepsy. The prolongation of QT interval, involved in cardiac arrhythmia-related SUDEP, may be precipitated by antiepileptic dru gs (AEDs). In this study, we evaluated the effects of phenobarbital and levetiracetam on PR–QTc intervals in patients with post-stroke seizures.

Methods

We performed an open-label, parallel group, prospective, multicenter study between June 2009 and December 2013 in patients older than 18 years of age with a clinical diagnosis of post-stroke seizure and treated with phenobarbital or levetiracetam. In order to exclude a role of cerebral post-stroke injury on modulation of PR and QTc intervals, patients with cerebral post-stroke injury and without seizures were also enrolled as controls.

Results

Interictal electrocardiography analysis revealed no significant difference in PR interval between patients treated with an AED (n = 49) and control patients (n = 50) (181.25 ± 12.05 vs. 182.4 ± 10.3 ms; p > 0.05). In contrast, a significantly longer QTc interval was recorded in patients treated with an AED compared with control patients (441.2 ± 56.6 vs. 396.8 ± 49.3 ms; p < 0.01). Patients treated with phenobarbital showed a significantly longer QTc interval than patients treated with levetiracetam (460.0 ± 57.2 vs. 421.5 ± 50.1 ms; p < 0.05).

Conclusions

The study reported that in patients with late post-stroke seizures, phenobarbital prolonged QTc interval more so than levetiracetam.

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Acknowledgments

The authors acknowledge the Groups of Progetto DAMA (Disabled Advanced Medical Assistance) dell’Azienda Ospedaliera di Cosenza for support in the collection of data for this study. The authors thank Gianni De Marco, nurse coordinator, and Roberto Siciliano, PhD, for technical support.Antonio Siniscalchi, Francesco Scaglione, Enzo Sanzaro, Francesco Iemolo, GiorgioAlbertini, Gianluca Quirino, Maria Teresa Manes,Santo Gratteri, Nicola Biagio Mercuri, Giovambattista De Sarro, and Luca Gallelli have no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. Department of Neurology, “Annunziata” Hospital, Cosenza, Italy

    Antonio Siniscalchi

  2. Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

    Francesco Scaglione

  3. Department of Neurology, “Guzzardi” Hospital di Vittoria-ASP di Ragusa, Ragusa, Italy

    Enzo Sanzaro & Francesco Iemolo

  4. IRCCS “San Raffaele Pisana”, Tosinvest Sanità, Rome, Italy

    Giorgio Albertini

  5. Department of Cardiology, “Annunziata” Hospital, Cosenza, Italy

    Gianluca Quirino & Maria Teresa Manes

  6. Department of Experimental Medicine, School of Medicine, University of Catanzaro, Catanzaro, Italy

    Santo Gratteri

  7. IRCCS-S. Lucia and Department of Neurology, University “Tor Vergata”, Rome, Italy

    Nicola Biagio Mercuri

  8. Clinical Pharmacology and Pharmacovigilance Unit, Department of Health Science, School of Medicine, Mater Domini University Hospital, University of Catanzaro, Viale Europa-Germaneto, 88100, Catanzaro, Italy

    Giovambattista De Sarro & Luca Gallelli

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  1. Antonio Siniscalchi
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Correspondence to Luca Gallelli.

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Siniscalchi, A., Scaglione, F., Sanzaro, E. et al. Effects of Phenobarbital and Levetiracetam on PR and QTc Intervals in Patients with Post-Stroke Seizure. Clin Drug Investig 34, 879–886 (2014). https://doi.org/10.1007/s40261-014-0243-9

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  • DOI: https://doi.org/10.1007/s40261-014-0243-9

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