New Evidence Links Calcium Channel Blockers to Increased Risk of Glaucoma

I'll have to talk to my doctor since I'm doing Nifedipine ER  and Losartan

Calcium channel blockers include:

• Amlodipine (Norvasc^®)
• Diltiazem (Cardiazem^®, Tiazac^®, Tiazac^® XC )
• Felodipine (Plendil^®)
• Nifedipine XL (Adalat XL^®)
• Verapamil (Isoptin^®, Isoptin^® SR, Verelan^®)

New Evidence Links Calcium Channel Blockers to Increased Risk of Glaucoma

Meta-analysis shows highest glaucoma risk with CCB monotherapy, reduced IOP with beta-blockers

by Charles Bankhead, Senior Editor, MedPage Today June 13, 2023

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) Consortiumopens in a new tab or window.

"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 Ophthalmologyopens in a new tab or window.

"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 glaucomaopens in a new tab or window risk by affecting optic nerve head perfusion, retinal ganglion cell survival, and aqueous humor outflow facility.

A study based on U.S. health claimsopens in a new tab or window 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 riskopens in a new tab or window include beta-blockers, metformin, statins, and bupropion. Additionally, some medications have been associated with higher IOPopens in a new tab or window, 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/torsemideopens in a new tab or window) 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.

• 

  Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures

The study was supported by multiple governmental, nonprofit, and philanthropic organizations.

Khawaja disclosed relationships with AbbVie, Aerie, Google Health, Novartis, Reichert, Santen, and Thea.

Patel disclosed no relevant relationships with industry.

Primary Source

Ophthalmology

Source Reference: opens in a new tab or windowVergroesen JE, et al "Association of systemic medication use with glaucoma and intraocular pressure: The E3 Consortium" Ophthalmol 2023; DOI: 10.1016/j.ophtha.2023.05.00

Blood pressure pill has potential to slow down Alzheimer’s disease

It is YOUR RESPONSIBILITY to get your doctor and stroke hospital involved with followup research into human subjects on this. Your stroke hospital will do nothing if you don't speak up. Because your stroke hospital has done no followup for decades is the reason nothing is ever solved in stroke.  Does your stroke hospital even know that stroke survivors need this?

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018

 

Blood pressure pill has potential to slow down Alzheimer’s disease

Laura Donnelly

,

The Telegraph•June 17, 2019

Research found that those given the pills for six months saw a 20 per cent increase in circulation of blood to the hippocampus - Naeblys 

A cheap blood pressure pill could slow down Alzheimer's disease by improving flow of blood to parts of the brain linked to memory, research suggests.

Dutch research found that those given the pills for six months saw a 20 per cent increase in circulation of blood to the hippocampus.

The drug, called Nilvadipine, is among a class of calcium channel blockers, costing less than 50 pence a day, which are commonly prescribed to reduce the risk of high blood pressure.

Scientists said the findings suggest that the decrease in blood flow in patients with Alzheimer’s disease could be reversed.

But they said it was too early to say if this could slow down progression of disease.

The study by Radboud University Medical Centre in Nijmegen, the Netherlands, involved 44 participants, half of which were given nilvadipine with half given a placebo for six months.

At the study's start and after six months, researchers measured blood flow to specific regions of the brain using a unique magnetic resonance imaging (MRI) technique.

Study lead author Professor Jurgen Claassen, of Radboud University Medical Centre in Holland, said: "This high blood pressure treatment holds promise as it doesn't appear to decrease blood flow to the brain, which could cause more harm than benefit.

"Even though no medical treatment is without risk, getting treatment for high blood pressure could be important to maintain brain health in patients with Alzheimer's disease."

Researchers said sample sizes were too small and follow-up time too short to reliably study the effects of this cerebral blood flow increase on structural brain measures and cognitive measures.

A larger study involving more than 500 people with mild to moderate Alzheimer's disease did not show the drug had an impact on the condition. However, those with mild symptoms of disease did have a slower decline in memory.

High blood pressure is already a known risk factor for dementia.

The condition affects 850,000 people in the UK, of which around six in ten have Alzheimer's disease.

Dr Laura Phipps, from Alzheimer’s Research UK, said: “We know high blood pressure is a risk factor for developing dementia but it’s unclear whether blood pressure-lowering drugs could improve memory and thinking in people with Alzheimer’s.

“There is strong evidence that there are things we can do to keep our brain healthy as we age. This includes keeping our blood pressure and cholesterol in check as well as not smoking, only drinking within the recommended limits, eating a balanced diet, and staying mentally and physically active.”

CCB Doesn't Help Cognition After Stroke MMSE scores no better with nimodipine than placebo after 6 months

Just because finding the solution to this is 'vexing' and complicated is no reason to give up.

CCB Doesn't Help Cognition After Stroke MMSE scores no better with nimodipine than placebo after 6 months

• by Kristina Fiore
  Associate Editor, MedPage Today February 23, 2017

HOUSTON -- Nimodipine didn't improve cognition when ischemic stroke patients with vascular mild cognitive impairment (MCI) started taking the calcium channel blocker within a week of their event, researchers reported here.
In a randomized controlled trial from 23 sites in China, patients had no differences in change in Mini-Mental State Exam (MMSE) scores at 6 months whether they were on the drug or placebo, Huaguang Zheng, MD, of Beijing Tiantan Hospital in China and colleagues reported at the International Stroke Conference meeting here.
"In our trial, we found that nimodipine didn't benefit vascular MCI patients, but it may have marginal positive effects on specific cognitive domains, such as executive function, and it won't increase the risk of stroke or other adverse events," Zheng said during a press briefing.
More than half of stroke patients develop vascular MCI during the first three months of follow-up, he explained, and about 30% to 50% will develop dementia within 5 years.
While there are currently no effective therapies for vascular MCI and dementia, some studies have suggested that nimodipine may have cognitive benefits, he said.
To assess whether that's the case, Zheng and colleagues randomized 654 patients to either placebo or to 30 mg nimodipine three times a day. The primary endpoint was the change in cognition function on the MMSE and on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) over 6 months.
Overall, outcomes were similar between the two groups, with no significant advantage for nimodipine, Zheng said.
There was, however, an advantage for nimodipine in terms of the proportion of patients who had an ADAS-Cog score of 0 or greater at 6 months (34% versus 47%), and there was some indication that the drug may benefit specific brain areas, particularly executive function, he noted.
Zheng added that nimodipine didn't increase the risk of stroke and other adverse events.
He acknowledged that the study was limited because it didn't evaluate Global Cognitive Index scores, neurological outcome, or subcortical dementia, and the sample size was too small.
Mark Alberts, MD, of Hartford Healthcare, said it was "reasonable to investigate" nimodipine given that it's been shown to potentially have neuroprotective effects. But the problem of cognitive decline following stroke is a "vexing issue" because the pathophysiology is so complicated.
"If you have a stroke, and you develop dementia after the stroke, is that vascular dementia related to the stroke? Having a stroke, you take out millions of neurons," he told MedPage Today. "Most people, including myself, think it's a combination, that there's some underlying degenerative process, and vascular disease on top of that is just accelerating it perhaps."
Alberts said it's best to focus on risk factor control in patients with cognitive impairment after a stroke -- treating diabetes, hypertension, and hypercholesterolemia, for instance. For patients who progress to dementia, he offers rehabilitation programs or the cholinesterase inhibitor donepezil (Aricept).
Amytis Towfighi, MD, of the University of Southern California and director of neurological services at the Los Angeles County department of health, agreed that risk factor control is the main therapeutic strategy for cognitive impairment following stroke.
"Currently there are no proven treatments. We don't know if medications that have been tested in Alzheimer's would be effective," she told MedPage Today. "Generally we recommend lifestyle changes -- the same things you would recommend to prevent stroke. Prevention is the key."

The study was supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China. Bayer provided additional support.
Zheng disclosed no financial relationships with industry.

• Primary Source

  International Stroke Conference

  Source Reference: Zheng H, et al "Efficacy and safety of nimodipine in vascular mild cognitive impairment: a randomized placebo controlled trial" ISC Meeting 2017; Abstract LB7.