Effect of Lomerizine Hydrochloride on Preventing Strokes in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.


Journal

Clinical neuropharmacology
ISSN: 1537-162X
Titre abrégé: Clin Neuropharmacol
Pays: United States
ID NLM: 7607910

Informations de publication

Date de publication:
Historique:
entrez: 18 9 2020
pubmed: 19 9 2020
medline: 9 7 2021
Statut: ppublish

Résumé

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow. This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method. When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3. Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.

Sections du résumé

BACKGROUND BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow.
SUBJECTS AND METHODS METHODS
This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method.
RESULTS RESULTS
When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3.
CONCLUSIONS CONCLUSIONS
Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.

Identifiants

pubmed: 32947425
doi: 10.1097/WNF.0000000000000402
pii: 00002826-202009000-00004
doi:

Substances chimiques

NOTCH3 protein, human 0
Piperazines 0
Receptor, Notch3 0
lomerizine DEE37CY4VO

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

146-150

Auteurs

Akiko Watanabe-Hosomi (A)

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Neurology, Fukuchiyama City Hospital, Kyoto, Japan.

Ikuko Mizuta (I)

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Takashi Koizumi (T)

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Neurology, North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Isao Yokota (I)

Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

Mao Mukai (M)

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Neurology, Kyoto Yamashiro General Medical Center, Kyoto, Japan.

Ai Hamano (A)

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Masaki Kondo (M)

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Akihiro Fujii (A)

Department of Neurology, Saiseikai Shiga Hospital, Shiga, Japan.

Masaru Matsui (M)

Department of Neurology, Otsu Red-Cross Hospital, Shiga, Japan.

Koushun Matsuo (K)

Department of Neurology, Omihachiman Community Medical Center, Shiga, Japan.

Keita Ito (K)

Department of Neurology, Hekinan Municipal Hospital, Aichi, Japan.

Satoshi Teramukai (S)

Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Kei Yamada (K)

Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Masanori Nakagawa (M)

Department of Neurology, North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Toshiki Mizuno (T)

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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Classifications MeSH