Risks of newly onset hemorrhagic stroke in patients with neovascular age‐related macular degeneration

Lee, Wan-Ju Annabelle; Cheng, Ching‐Lan; Lee, Cheng‐Han; Yang, Yea‐Huei Kao; Lin, Swu–Jane; Hsieh, Cheng‐Yang

doi:10.1002/pds.4299

Cited by 8 publications

(3 citation statements)

References 41 publications

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“…Another potential explanation is that AMD itself that is active enough to require ranibizumab treatment, rather than the direct effect of ranibizumab exposure, may be a risk factor for hemorrhagic stroke. Previous studies have reported that late or neovascular AMD is strongly associated with intracerebral hemorrhage but not with cerebral infarction [17,18]. Further clinical studies are warranted to confirm our results and investigate the mechanisms.…”

Section: Discussionsupporting

confidence: 74%

Risk of stroke associated with intravitreal ranibizumab injections in age-related macular degeneration: a nationwide case-crossover study

Kim

et al. 2020

Eye

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Objective To evaluate the risk of stroke associated with intravitreal ranibizumab in age-related macular degeneration (AMD). Methods A nationwide retrospective case-crossover study was performed using data from the Korean National Health Insurance Service (KNHIS) database, which included patients with exudative AMD in South Korea (n = 41,860). The index date was the date of hospitalization for stroke. We defined the case period as 60 days and four control periods before the index date. A pharmacy prescription database was searched for ranibizumab use during the case and control periods. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with a conditional logistic regression model. Results A total of 865 patients with AMD and incident stroke were included. Of all the patients, 12.02% had been treated during the preceding 60-day case period, compared with 9.25-10.29% during control periods. The adjusted OR of stroke associated with intravitreal ranibizumab during the case period was 1.285 (95% CI 0.979-1.686) (p = 0.07). In the subgroup analysis, the risk of hemorrhagic stroke had an OR of 2.252 (95% CI 1.068-4.749, p = 0.033). Further analyses based on patient gender, age, and different risk periods of 15 and 30 days yielded no increase in the risk of stroke associated with intravitreal ranibizumab. Conclusions This case-crossover analysis revealed no evidence of increased risk of hospitalization for stroke within 60 days of intravitreal ranibizumab injection in AMD patients. A secondary analysis indicated the possibility of an increased risk of hemorrhagic stroke, with borderline significance. Further research is needed regarding the underlying biological mechanisms and drug safety.

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Section: Discussionsupporting

confidence: 74%

Risk of stroke associated with intravitreal ranibizumab injections in age-related macular degeneration: a nationwide case-crossover study

Kim

et al. 2020

Eye

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“…Cigarette smoking also could modify the genetic effect of LOC387715 rs110490924 on polypoidal choroidal vasculopathy [38]. In addition, previous cohort study showed that the nAMD significantly increased the risk of stroke (HR=1.3), particularly hemorrhagic stroke (HR=1.70) [39]. These findings would help to understand the molecular mechanisms how smoking affect stroke and promote tobacco control strategy in preventing the onset of stroke.…”

Section: Discussionmentioning

confidence: 90%

HTRA1 Variants and the Interaction with Smoking Confer the Genetic Susceptibility to Ischemic Stroke

Tian¹,

Tang²,

Yang³

et al. 2021

Int. J. Med. Sci.

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High temperature requirement protein A1 (HtrA1) was identified as the causative gene of autosomal recessive arteriopathy and associated with lacunar ischemic stroke (IS) in European. This study aimed at evaluating the association of HTRA1 with IS and four tagging single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of 4,098 Chinese. The mRNA level of HTRA1 in 72 IS cases and 72 hypertension controls were measured and compared. In whole population, SNP rs2268350 (C>T) was significantly associated with IS incidence (P=0.034). Stratification analysis observed significant association of rs2268350 in male, smoking and drinking populations, rs2672587 (C>G) in smoking and nonsmoking populations and rs3793917 (C>G) in smoking, nonsmoking and nondrinking populations with stroke respectively (P<0.05). The additive interaction and multiplicative interaction between rs2268350 and smoking were both of significant (P<0.05) after adjustment for the covariates. There was a cumulated risk of IS among genotypes of rs3793917 (P=0.009) and rs2672587 (P=0.047) in smoking population. The mRNA level of HTRA1 in non-smokers with rs2268350 CC was significantly higher than smokers with rs2268350 CT/TT (P=0.046) in IS cases. Our findings support that HTRA1 confers the genetic susceptibility to IS and smoking might modify the genetic effect of HTRA1 on IS by suppressing HTRA1 mRNA expression.

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“…Fourth, due to the different ethnicities, Asian population tends to have more hemorrhagic events than Caucasians. 35 Asians had more polypoidal choroidal vasculopathy (PCV) than classic nAMD. 36 The important characteristic of PCV is a peculiar macular hemorrhagic with recurrent sub-retinal and sub-RPE bleeding.…”

Section: Discussionmentioning

confidence: 99%

Risk of age‐related macular degeneration in aspirin users and non‐aspirin users: A population‐based cohort study in Taiwan

Lee

Yang

Cheng

2020

Pharmacoepidemiology and Drug

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BackgroundThe association between cardioprotective aspirin and risk of age‐related macular degeneration (AMD) is still controversial up to date. We aimed to analyze the risk of AMD between aspirin users and non‐aspirin users.MethodThis was a retrospective cohort study by using claims data from the National Health Insurance Research Database. Patients aged more than 45 years old who initiated aspirin during 2002 to 2012 were followed till 2013. We first selected an age and sex‐matched cohort, then identified aspirin users and non‐aspirin users as propensity score‐matched cohort. Cox proportional hazard regression model was applied to compare their hazards and 95% confidence intervals. Incidence of newly developed AMD, neovascular AMD, and other‐AMD was calculated.ResultsWe identified 204 085 regular aspirin users and 478 048 non‐aspirin users from our datasets. The univariate HR was 2.85 (95% CI, 2.75‐2.96), and the multivariate HR was 2.54 (95% CI, 2.44‐2.65). In the PS‐matched cohort, the HR was 2.38 (95% CI, 2.25‐2.52). The incidence of aspirin users for AMD risk was 11.95 per 1000 person‐year, while the incidence of non‐aspirin users was only 3.92 per 1000 person‐year.ConclusionPatients with regular use of aspirin had higher risk in developing AMD compared to non‐aspirin users and suggest to have regular visual acuity and funduscopic examination.

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Risks of newly onset hemorrhagic stroke in patients with neovascular age‐related macular degeneration

Abstract: Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype.

Cited by 8 publications

References 41 publications

Risk of stroke associated with intravitreal ranibizumab injections in age-related macular degeneration: a nationwide case-crossover study

Risk of stroke associated with intravitreal ranibizumab injections in age-related macular degeneration: a nationwide case-crossover study

HTRA1 Variants and the Interaction with Smoking Confer the Genetic Susceptibility to Ischemic Stroke

Risk of age‐related macular degeneration in aspirin users and non‐aspirin users: A population‐based cohort study in Taiwan

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