Calcium-channel blocker use ups glaucoma prevalence

Use of calcium-channel blockers (CCBs) appears to increase the risk of developing glaucoma, suggests a study. In addition, use of systemic beta blockers is associated with lower intraocular pressure (IOP).

“Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications,” the researchers said. “Determining causality of the CCB association should be a research priority.”

This meta-analysis included 11 population-based cohort studies of the European Eye Epidemiology Consortium, with 143,240 participants for glaucoma analyses and 47,177 participants for IOP analyses. Glaucoma ascertainment and IOP measurement methods were based on individual study protocols.

The investigators explored the associations of four categories of systemic medications (ie, antihypertensive medications: beta blockers, diuretics, CCBs, α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers) with glaucoma prevalence and IOP.

Using random effects meta-analyses, the investigators pooled the results of multivariable regression analyses of each study. They also examined the relationship with antidiabetic medications in participants with diabetes only.

Meta-analyses of adjusted multivariable models revealed the association of CCB use with a higher prevalence of glaucoma (odds ratio [OR], 1.23, 95 percent confidence interval [CI], 1.08‒1.39). This association was more pronounced for monotherapy of CCBs, with direct cardiac effects (OR, 1.96, 95 percent CI, 1.23‒3.12). [Ophthalmology 2023;130:893-906]

Other antihypertensive drugs, lipid-lowering agents, antidepressants, or antidiabetic medications showed no significant association with glaucoma.

“A potentially harmful association of CCBs for glaucoma is particularly noteworthy, because this is a commonly prescribed class of medication,” the investigators said. “If further studies confirm a casual nature for this association, this may inform alternative treatment strategies for patients with hypertension who have, or are at risk of having, glaucoma.”

In addition, use of systemic beta blockers contributed to a lower IOP (β coefficient, ‒0.33 mm Hg, 95 percent CI, ‒0.57 to ‒0.08). Monotherapy of both selective (β coefficient, ‒0.45 mm Hg, 95 percent CI,‒0.74 to ‒0.16) and nonselective systemic beta blockers (β coefficient, ‒0.54, 95 percent CI, ‒0.94 to ‒0.15) correlated with lower IOP.

There was also a suggestive association seen between use of high-ceiling diuretics and lower IOP (β coefficient, ‒0.30 mm Hg, 95 percent CI, ‒0.47 to ‒0.14) but not when used as monotherapy.

Other antihypertensive drugs, lipid-lowering agents, antidepressants, or antidiabetic medications were not significantly associated with IOP.

Systemic hypotension

Earlier studies suggested that CCB use at bedtime, rather than in the morning, was more effective at reducing BP. [Chronobiol Int 2013;30:280-314; Chronobiol Int 2010;27:1629-1651; J Am Soc Nephrol 2011;22:2313-2321; Diabetes Care 2011;34:1270-1276; Am J Hypertens 2020;33:987-989]

In this regard, existing evidence showed that nocturnal systemic hypotension could potentially elevate the risk of glaucoma progression. [Ophthalmology 2014;121:2004-2012; Surv Ophthalmol 1999;43:S10-S16; Sci Rep 2021;11:206]

“Thus, this may explain the association between CCBs and increased glaucoma prevalence if CCBs are taken preferentially at bedtime,” the investigators said. “In the present study, time of medication use was not known. Therefore, we were not able to provide evidence for this hypothesis.”