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Calcium Channel Blockers Linked to Higher Glaucoma Risk

A new retrospective analysis of data from over 400,000 UK Biobank participants has revealed that calcium channel blockers (CCBs), but not other antihypertensive agents, were associated with an increased prevalence of glaucoma and related traits.

The study, published in JAMA Ophthalmology, suggested that CCBs may represent "an important modifiable risk factor for glaucoma", potentially through a mechanism independent of intraocular pressure.

The researchers, led by Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, pointed out that CCBs are prescribed for up to 40% of patients with hypertension. An increased incidence of glaucoma requiring a procedural treatment had been noted to be associated with CCB use in exploratory studies of US insurance claims data, and several population-based studies had demonstrated similar associations. 

So, to further investigate the possible link, they examined data from UK Biobank participants who had various types of opthalmic data collected between 2006 and 2010 for retrospective analysis and comparison with baseline CCB use.

Participants were 427,480 adults who had complete data for glaucoma status. They had a median age of 58 (range 50-63) and 54.1% were women. Of the total, 97,100 had intraocular pressure (IOP ) measurements recorded, and 41,023 had optical coherence tomography (OCT)-derived inner retinal layer thicknesses.

Glaucoma Risk Increased with CCBs but Not Other Antihypertensives

Among the total sample, 114,311 (26.7%) had a history of physician-diagnosed systemic hypertension and there were 33,175 CCB users (7.8%), most of them (89%) with a hypertension diagnosis. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, glaucoma risk was associated on regression analysis with use of any antihypertensive (odds ratio [OR], 1.29 [95% CI, 1.10 to 1.52]; P = .002). 

There was no significant association with use of diuretics (OR 1.03), renin-angiotensin-aldosterone (RAS) inhibitors (OR, 1.12), or systemic β-blockers, but use of CCBs was associated with almost a 40% increased risk of a glaucoma diagnosis (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). 

CCBs were also associated with thinner macular ganglion cell–inner plexiform layer (mGCIPL) and macular retinal nerve fiber layer (mRNFL) on OCT, which the team said provided a "structural basis" to support the association with glaucoma. However there was no association between CCB use and IOP, suggesting that a pressure-independent mechanism of glaucomatous neurodegeneration may be involved. 

Consider Changing CCB Therapy if Glaucoma Progresses

The researchers concluded: "Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care."

According to Moorfields , over half a million people in the UK — about 2% of those over 40 — have glaucoma, and the condition is responsible for 10% of cases of blindness. Other Moorfields research has suggested that while CCBs increase the risk of glaucoma, selective serotonin reuptake inhibitors may reduce the risk of primary open angle glaucoma by around 30%.

Asked to comment by Medscape News UK, charity Blood Pressure UK said: "While the study findings support an association between CCB use and glaucoma, it is important to emphasise that there is, to date, no evidence that CCB use is directly responsible for higher glaucoma risk. 

"High blood pressure and glaucoma are both common health conditions in the UK. CCB medications, such as nifedipine and amlodipine, have been used safely for 30-40 years to reduce the risk of heart attack, stroke, and kidney disease caused by high blood pressure; they account for around 4% of all primary care prescriptions. 

"Blood pressure UK wants to assure patients that the benefits of CCB medications far outweigh any potential association of risk, and we urge patients not to stop these or any other blood pressure medications without first consulting their doctors."

"Exciting Findings" but Association is Not Causality

Also commenting for Medscape News UK on behalf of the Royal College of Ophthalmologists, Dr Ricardo De Sousa Peixoto, a consultant ophthalmic surgeon with a special interest in glaucoma and cataract surgery, pointed out that the findings on links between CCB and glaucoma were independent of intraocular pressure, which is "currently the main modifiable risk factor for glaucoma". 

He said: "Although statistically strong, this research has only demonstrated association, but not causality. Importantly, researchers did not consider timing of medication, which may be important given that antihypertensives taken at night may lower the blood pressure to levels that threaten optic disc blood supply, potentially leading to non-glaucomatous optic neuropathy.  

"These exciting findings need to be substantiated by randomised control trials comparing hypertension patients undergoing CCBs and other blood pressure medications. If confirmed, this may add an extra layer to the guidelines relating to hypertension treatment, and glaucoma risk factors may play an important role in the choice of first line antihypertensive drug."

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