Candidate drugs for preventive treatment of unruptured intracranial aneurysms: A cross-sectional study

Establishment of drug therapy to prevent rupture of unruptured intracranial aneurysms (IAs) is needed. Previous human and animal studies have gradually clarified candidate drugs for preventive treatment of IA rupture. However, because most of these candidates belong to classes of drugs frequently co...

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Bibliographic Details
Published in:PloS one 2021-02, Vol.16 (2), p.e0246865-e0246865
Main Authors: Shimizu, Kampei, Imamura, Hirotoshi, Tani, Shoichi, Adachi, Hidemitsu, Sakai, Chiaki, Ishii, Akira, Kataoka, Hiroharu, Miyamoto, Susumu, Aoki, Tomohiro, Sakai, Nobuyuki
Format: Article
Language:English
Subjects:
Adrenergic receptors
Aneurysm
Aneurysms
Angiotensin
Angiotensin II
Angiotensin II receptor blockers
Angiotensin-converting enzyme inhibitors
Anti-inflammatory agents
Anticoagulants
Aspirin
Biology and Life Sciences
Blood platelets
Calcium
Calcium channel blockers
Cardiovascular system
Chemotherapy
Coenzyme A
Complications
COX-2 inhibitors
Cross-sectional studies
Cyclooxygenase-2
Datasets
Dipeptidyl-peptidase IV
Drug development
Drug dosages
Drug therapy
Editing
Eicosapentaenoic acid
Enzyme inhibitors
Estrogen receptors
Estrogens
Glucocorticoids
Graduate schools
Graduate studies
Health care facilities
Hospitals
Hydroxymethylglutaryl-CoA reductase
Indapamide
Inflammation
Intracranial aneurysms
Medicine
Medicine and Health Sciences
Methodology
Modulators
Neuromodulation
Neurosurgery
Nonsteroidal anti-inflammatory drugs
Patients
Peptidase
Peptidases
Peptidyl-dipeptidase A
Pharmacology
Physical Sciences
Prevention
Prostaglandin endoperoxide synthase
Receptors
Receptors (physiology)
Reductases
Renin
Research and Analysis Methods
Sensitivity analysis
Serotonin
Statins
Testing
University graduates
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Summary:Establishment of drug therapy to prevent rupture of unruptured intracranial aneurysms (IAs) is needed. Previous human and animal studies have gradually clarified candidate drugs for preventive treatment of IA rupture. However, because most of these candidates belong to classes of drugs frequently co-administered to prevent cardiovascular diseases, epidemiological studies evaluating these drugs simultaneously should be performed. Furthermore, because drugs included in the same class may have different effects in terms of disease prevention, drug-by-drug assessments are important for planning intervention trials. We performed a cross-sectional study enrolling patients diagnosed with IAs between July 2011 and June 2019 at our institution. Patients were divided into ruptured or unruptured groups. The drugs investigated were selected according to evidence suggested by either human or animal studies. Univariate and multivariate logistic regression analyses were performed to assess the association of drug treatment with rupture status. We also performed drug-by-drug assessments of the association, including dose-response relationships, with rupture status. In total, 310 patients with ruptured and 887 patients with unruptured IAs were included. Multivariate analysis revealed an inverse association of statins (odds ratio (OR), 0.54; 95% confidence interval (CI) 0.38-0.77), calcium channel blockers (OR, 0.41; 95% CI 0.30-0.58), and angiotensin II receptor blockers (ARBs) (OR, 0.67; 95% CI 0.48-0.93) with ruptured IAs. Moreover, inverse dose-response relationships with rupture status were observed for pitavastatin and rosuvastatin among statins, benidipine, cilnidipine, and amlodipine among calcium channel blockers, and valsartan, azilsartan, candesartan, and olmesartan among ARBs. Only non-aspirin non-steroidal anti-inflammatory drugs were positively associated with ruptured IAs (OR, 3.24; 95% CI 1.71-6.13). The present analysis suggests that several types of statins, calcium channel blockers, and ARBs are candidate drugs for preventive treatment of unruptured IAs.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0246865