New Evidence Links Calcium Channel Blockers to Increased Risk of Glaucoma

Use of calcium channel blockers (CCBs), particularly cardioselective agents, had a modest but statistically significant association with glaucoma, a large meta-analysis showed.

Overall, patients with a history of CCB treatment had a 23% higher likelihood of developing glaucoma as compared with individuals who never used the antihypertensives. The likelihood almost doubled among patients who received single-agent cardioselective CCBs. In contrast, beta-blocker therapy was associated with modestly reduced intraocular pressure (IOP), which is associated with a reduced risk of glaucoma.

A number of other commonly used medications had no clear associations with glaucoma or IOP, including lipid-lowering drugs, antidepressants, and diabetes medications, reported Anthony Khawaja, MD, PhD, of University College London, and colleagues in the European Eye Epidemiology (E3) Consortium.

“While our novel findings require further studies to determine whether the associations are causal, these findings will be of interest to physicians caring for glaucoma patients with systemic comorbidities,” the authors stated in Ophthalmology.

“A potentially harmful association of CCBs for glaucoma is particularly noteworthy, as this is a commonly prescribed class of medication,” they added. “If further studies confirm a casual nature for this association, this may inform alternative treatment strategies for hypertensive patients with, or at risk of, glaucoma.”

Adds to Existing Evidence

The findings add to evidence from previous studies showing that systemic beta-blockers lower IOP, and at least one prior study has shown an association between CCBs and glaucoma, said Roma Patel, MD, MBA, of Baylor College of Medicine and Ben Taub Hospital in Houston, and a clinical spokesperson for the American Academy of Ophthalmology.

“The study’s contribution is one of power,” Patel told MedPage Today via email. “The dataset used for this analysis represented over 143,000 individuals with glaucoma. Because of the size of population studied, this study was able to find that an even stronger association between CCBs with direct cardiac effects and glaucoma versus analysis of all CCBs and glaucoma. Perhaps this will help researchers figure out if there is a causal link. We know that glaucoma is ultimately related to dysfunction and death of the retinal ganglion cells. We don’t concretely know the effects of calcium blockade at that level so it poses a good research question.”

With respect to implications for clinical practice, Patel added, “I believe it’s fair to tell patients there is a known association for calcium channel blockers and glaucoma but we don’t fully understand why and there is no evidence of a causal relationship. If the patient chooses to discuss with their PCP [primary care physician] or cardiologist about a different treatment regimen for their cardiac issue, that is up to the patient. But I am not encouraging that conversation with my patients.”

“I do encourage my patients to talk to their PCP or cardiologist about avoiding evening anti-hypertensive medications because we do know that low blood pressure overnight can lead to glaucoma progression,” she said. “It’s important to remember that the eye lives within the human body and all of our systems are connected. But if the cardiologist feels that a certain medicine is warranted, I recommend we follow that recommendation because we all know that the eye can’t live without the heart.”

Glaucoma is the leading cause of irreversible vision impairment worldwide, and IOP currently is the only modifiable risk factor for glaucoma onset and progression, Khawaja and co-authors noted. Several types of medication are known or suspected of modulating glaucoma risk by affecting optic nerve head perfusion, retinal ganglion cell survival, and aqueous humor outflow facility.

A study based on U.S. health claims suggested that selective serotonin reuptake inhibitors were associated with a reduced risk of primary open-angle glaucoma and CCBs with an increased risk. Other medications that may influence glaucoma risk include beta-blockers, metformin, statins, and bupropion. Additionally, some medications have been associated with higher IOP, including angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), statins, and sulfonylureas.

“For many of the cited associations, there have been inconsistent findings between studies, and few studies have accounted for polypharmacy or important confounders,” Khawaja and colleagues noted.

Clarifying Study

To continue the line of research, investigators in the E3 Consortium performed a meta-analysis of 11 European cohort studies involving a total of 143,240 participants, all of whom were included in analyses of glaucoma associations. Analyses of IOP included 47,177 participants. Medication use encompassed multiple types of antihypertensives, lipid-lower medications, antidepressants, and antidiabetic medications (limited only to participants with diagnosed diabetes). For antihypertensives, the investigators distinguished monotherapy from combination therapy.

Multivariable analyses showed that any CCB use was associated with a glaucoma OR of 1.23 (95% CI 1.08-1.39) versus no use. Patients who received CCB monotherapy had a glaucoma OR of 1.96 (95% CI 1.23-3.12). No other medications were clearly associated with glaucoma, the authors reported. Systemic beta-blockers were associated with marginally lower IOP (-0.33 mmHg, 95% CI -0.57 to -0.08). Monotherapy with selective beta-blockers was associated with a 0.45 mmHg reduction in IOP (95% CI -0.74 to -0.16) and non-selective agents with a 0.54 mmHg reduction in IOP (95% CI -0.94 to -0.15).

High-ceiling diuretics (such as furosemide and torasemide/torsemide) had a “suggestive” association with lower IOP (-0.30 mmHg, 95% CI -0.47 to -0.14), but not when used as monotherapy.

None of the other medications included in the analysis had associations with IOP.