Retention rate of first antiepileptic drug in poststroke epilepsy: A nationwide study

Larsson, David; Åsberg, Signild; Kumlien, Eva; Zelano, Johan

doi:10.1016/j.seizure.2018.11.013

Cited by 27 publications

(41 citation statements)

References 26 publications

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“…To the Editor, A thorough study has been carried out by Larsson et al [1] based on nation-wide registers, which provides valuable information on the longterm retention rates of the most often prescribed antiepileptic drugs (AEDs) in post-stroke epilepsy. Computation of the retention rates was estimated by using the Kaplan-Meier (KM) methodology.…”

Section: Computation Of Antiepileptic Drug Retention Rates In the Prementioning

confidence: 99%

“…Computation of the retention rates was estimated by using the Kaplan-Meier (KM) methodology. The authors excluded a priori patients who died during the first two months after stroke, while patients who died during the study period (> 2 months post-stroke) were censored [1]. This calls for some methodological discussion.…”

Section: Computation Of Antiepileptic Drug Retention Rates In the Prementioning

confidence: 99%

“…Indeed, it is impossible that AED non-retention occurs after death. Given that the estimated 2-and 5-year survival after the first seizure diagnosis in post-stroke epilepsy was 66% and 45% respectively [4], a substantial number of patients were censored due to death in the study by Larsson et al [1]. Censoring these patients leads to an overestimation of the KM survival curve [3].…”

Section: Computation Of Antiepileptic Drug Retention Rates In the Prementioning

confidence: 99%

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Computation of antiepileptic drug retention rates in the presence of a competing risk

Meer

Fiocco

Koekkoek

et al. 2019

Seizure

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Section: Computation Of Antiepileptic Drug Retention Rates In the Prementioning

confidence: 99%

Section: Computation Of Antiepileptic Drug Retention Rates In the Prementioning

confidence: 99%

Section: Computation Of Antiepileptic Drug Retention Rates In the Prementioning

confidence: 99%

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Computation of antiepileptic drug retention rates in the presence of a competing risk

Meer

Fiocco

Koekkoek

et al. 2019

Seizure

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“…Cerebrovascular disease, particularly stroke, is one of the most common causes of new‐onset epilepsy among older adults with identified epilepsy etiology . Considerations for the antiepileptic drug (AED) treatment of post‐stroke epilepsy include the patient's susceptibility to age‐related side effects and potential drug‐drug interactions . Treatment with non‐enzyme‐inducing AEDs may be preferable, as enzyme induction may interfere with secondary stroke prophylaxis and exacerbate vascular risk .…”

Section: Introductionmentioning

confidence: 99%

Lacosamide in patients with epilepsy of cerebrovascular etiology

et al. 2020

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Objectives:To assess tolerability and efficacy of lacosamide in adults with cerebrovascular epilepsy etiology (CVEE). Materials and methods:Exploratory post hoc analyses of a double-blind, initial monotherapy trial of lacosamide vs carbamazepine-controlled release (carbamazepine-CR) (SP0993; NCT01243177); a double-blind conversion to lacosamide monotherapy trial (SP0902; NCT00520741); and an observational study of adjunctive lacosamide added to one antiepileptic drug (SP0973 VITOBA; NCT01098162). Patients with CVEE were identified based on epilepsy etiology recorded at baseline. Results: In the initial monotherapy trial, 61 patients had CVEE (lacosamide: 27; carbamazepine-CR: 34). 20 (74.1%) patients on lacosamide (27 [79.4%] on carbamazepine-CR) reported treatment-emergent adverse events (TEAEs), most commonly (≥10%) headache, dizziness, and fatigue (carbamazepine-CR: headache, dizziness). A numerically higher proportion of patients on lacosamide than carbamazepine-CR completed 6 months (22 [81.5%]; 20 [58.8%]) and 12 months (18 [66.7%]; 17 [50.0%]) treatment without seizure at last evaluated dose. In the conversion to monotherapy trial, 26/30 (86.7%) patients with CVEE reported TEAEs, most commonly (≥4 patients) dizziness, convulsion, fatigue, headache, somnolence, and cognitive disorder. During lacosamide monotherapy, 17 (56.7%) patients were 50% responders and six (20.0%) were seizure-free. In the observational study, 36/83 (43.4%) patients with CVEE reported TEAEs, most commonly (≥5%) fatigue and dizziness. Effectiveness was assessed for 75 patients. During the last 3 months, 60 (80%) were 50% responders and 42 (56.0%)were seizure-free. Conclusions:These exploratory post hoc analyses suggested lacosamide was generally well tolerated and effective in patients with CVEE, with data from the initial monotherapy trial suggesting numerically better efficacy than carbamazepine-CR. K E Y W O R D Santiepileptic drugs, elderly, epilepsy, lacosamide, seizures, stroke

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We are very grateful for the comments of van der Meer et al on our paper describing retention rates of the first prescribed antiepileptic drugs (AEDs) in a large cohort of patients with poststroke epilepsy [1]. We decided to use Kaplan Meier (KM) analysis for several reasons.

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Reply to ‘Computation of antiepileptic drug retention rates in the presence of a competing risk’

Zelano

2019

Seizure

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We are very grateful for the comments of van der Meer et al. on our paper describing retention rates of the first prescribed antiepileptic drugs (AEDs) in a large cohort of patients with poststroke epilepsy [1]. We decided to use Kaplan Meier (KM) analysis for several reasons. Firstly, the basic assumption of a KM analysis, that censoring (because of death) is independent of the outcome (discontinuation of an AED) seems reasonable. Secondly, one of the benefits of a KM analysis is that it allows easy comparison with the existing literature. KM analyses are widely used for estimates of retention rates of AEDs, also in the elderly [2][3][4].Furthermore, we are uncertain that a competing risk analysis would be the most informative model for our research question. The patient and the neurologist are typically interested in the likelihood of discontinuation under the assumption that no competing death will occur. In addition, we are doubtful that a competing risk analysis would be appropriate for our data, since detection of the competing events would not be equal. Our conservative method of defining discontinuation as absence of prescription renewal in 12 months means that patients must have survived for at least this time to allow detection of discontinuation. Put differently, for 12 months following each renewal, death and discontinuation are not competing events -only death can occur. For this reason, the non-informative censoring at death in KM seems more appropriate. It is true that KM estimates become less precise and that event probability may be overestimated towards the end of the analysis. We think most readers are well aware of this drawback of a KM analysis.Competing risks are an important concept. The points raised by the authors are informative and enhance the understanding of our paper. However, we think the original KM analyses are better suited to our material. References[1] Larsson D, Asberg S, Kumlien E, Zelano J. Retention rate of first antiepileptic drug in poststroke epilepsy: A nationwide study. Seizure 2019;64:29-33. [2] Villanueva V, Giraldez BG, Toledo M, De Haan GJ, Cumbo E, Gambardella A, De Backer M, Joeres L, Brunnert M, Dedeken P, Serratosa J. Lacosamide monotherapy in clinical practice: A retrospective chart review. Acta Neurol Scand 2018;138:186-94. [3] Sarkis RA, Nicolas J, Lee JW. Tolerability of lacosamide or zonisamide in elderly patients with seizures. Seizure 2017;49:1-4. [4] Werhahn KJ, Trinka E, Dobesberger J, Unterberger I, Baum P, Deckert-Schmitz M, Kniess T, Schmitz B, Bernedo V, Ruckes C, Ehrlich A, Kramer G. A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with newonset focal epilepsy. Epilepsia 2015;56:450-9.

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Retention rate of first antiepileptic drug in poststroke epilepsy: A nationwide study

Cited by 27 publications

References 26 publications

Computation of antiepileptic drug retention rates in the presence of a competing risk

Computation of antiepileptic drug retention rates in the presence of a competing risk

Lacosamide in patients with epilepsy of cerebrovascular etiology

Reply to ‘Computation of antiepileptic drug retention rates in the presence of a competing risk’

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