Geriatric pharmacotherapy: Sneak peek at Beers update, key research in 2015
Preview of updated Beers list, statins in older men without heart disease, excessive lowering of BP in older adults, anticholinergenic drugs and dementia risk, new shingles vaccine
A preview of the updated Beers list of inappropriate drugs, continuing debate about whether statins benefit older men without heart disease, and the concern that excessive lowering of blood pressure (BP) in older patients might cause more harm than good were among topics of interest to pharmacists at the American Geriatrics Society’s (AGS) 2015 Annual Scientific Meeting.
Other key research in 2015 includes results from the Adult Changes in Thought study group1 demonstrating that cumulative anticholinergic use is associated with a higher risk for incident dementia, and results from the ZOE-50 trial2 using a new herpes zoster vaccine against shingles demonstrating effectiveness across various age groups, including those older than 70 years.
Revised Beers criteria to be released
A preview of the revised Beers criteria was presented at a plenary symposium during the AGS annual meeting. At press time, the final version was scheduled for release this month.
Several proposed changes in the Beers criteria are of interest. The update removes the longstanding recommendation to avoid nitrofurantoin in patients with a creatinine clearance level lower than 60 mL/min;3 however, AGS continues to recommend avoiding chronic use of nitrofurantoin because of the risk of pulmonary fibrosis. One new recommendation is to avoid combining multiple anticholinergic medications because of a potential increase in risk for cognitive decline.
Another new recommendation proposed by AGS is to avoid the use of proton pump inhibitors (PPIs) for more than 8 weeks in older patients. Patients at high risk for gastrointestinal disease will likely be excluded, such as chronic users of NSAIDs, those with Barrett’s esophagus, hypersecretory states, or those demonstrating a need for PPI maintenance therapy. The recommendation to limit the use of PPIs to no more than 8 weeks is based on studies showing an increased risk for Clostridium difficile infection, reduced bone mineral density, and increased fracture risk associated with chronic PPI use in older patients.
The updated Beers list continues to emphasize that medications listed are potentially, but not definitely, inappropriate in older adults. The Beers criteria have always been intended to supplement or support clinical judgment. Thus, concern was expressed at the meeting that the criteria are being used by insurance companies and other third-party payers to deny use or require prior authorization, even if the prescriber is aware of the risks and benefits.
Statins in older men without heart disease
A large epidemiological study presented at the AGS annual meeting suggested that men older than 70 years with no previous cardiovascular disease who use statins had a nonsignificant 10% reduction in myocardial infarction, stroke, and revascularization as a combined endpoint. These results add to a growing body of evidence questioning the benefit of statin drugs for primary prevention in low-risk patients. It is unknown if the results from this important but unpublished study can be extrapolated to older women.
The most recent lipid-lowering guidelines from the American College of Cardiology and the American Heart Association are mostly silent with respect to statin use as primary prevention for patients older than 75 years. A consensus is emerging, however, that the modest benefits of statin drugs in older patients without cardiovascular disease (primary prevention) probably do not outweigh the risk and costs of these drugs. For example, it is well known that muscle toxicity, such as myositis and potentially fatal rhabdomyolysis, is more common in older patients than in younger adults.
Excessive lowering of BP in older adults
The AGS meeting also featured results from a longitudinal study of 5,157 patients with hypertension who were older than 65 years.3 Based on this study, older patients do not benefit from aggressive BP lowering to systolic pressures below 120 mm Hg. This lower BP threshold was associated with increased risk for falls.
The guidelines for treating hypertension from the Eighth Joint National Committee recommend treating systolic blood pressure to below 150 mm Hg for patients aged 60 years and older without diabetes or chronic kidney disease. There are little data, however, to define the lower thresholds of systolic pressure targets in older patients. This study adds to recent data demonstrating that progression of cognitive decline is greater in older patients with dementia when systolic pressures are below 128 mm Hg.4
While a generation of adults has been taught that “normal” blood pressure is 120/80 mm Hg, a consensus is emerging that a systolic blood pressure of 120 mm Hg or less is too low in older patients. Overly aggressive blood pressure should generally be avoided in patients taking multiple vasodilators, or those who are already experiencing orthostatic hypotension. Clearly, symptomatic orthostatic hypotension can predispose older patients to falls and potentially serious fractures.
AGS held its 2015 annual meeting on May 14–17 in National Harbor, MD. For more information about research presented there, visit the AGS meeting website (www.americangeriatrics.org/annual_meeting/attendees).
Anticholinergic drugs, dementia risk: New data
“There are ongoing and newer concerns about medications, such as benzodiazepines and anticholinergic drugs, in the elderly,” said C. Wayne Weart, PharmD, BCPS, FASHP, FAPhA, Professor of Clinical Pharmacy and Outcome Sciences at the Medical University of South Carolina, and the APhA DrugInfoLine Section Advisor for Gastroenterology.
A prospective population-based cohort study using data from the Adult Changes in Thought study group1 involved 3,434 participants aged 65 years or older with no dementia at study entry. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, with a majority developing Alzheimer disease. The adjusted hazard ratio for cumulative anticholinergic use versus nonuse was 0.92 (95% CI 0.74–1.16).
A 10-year cumulative dose–response relationship was observed for dementia in patients receiving anticholinergic drugs. The increased risk for dementia remained consistent across anticholinergic subclasses, with an increased risk found for people with high use of anticholinergic drugs, such as first-generation antihistamines and anticholinergic drugs used to treat urinary bladder disorders.
This study suggested that patients using drugs such as oxybutynin 5 mg daily or doxepin 10 mg daily for more than 3 years would have a greater risk for dementia. “This has important implications for pharmacists, since many anticholinergic drugs are also available over-the-counter,” said Weart.
While this study did conclude that higher cumulative anticholinergic use is associated with an increased risk for dementia, this cohort study was not a randomized controlled trial designed to prove a causal link between development of Alzheimer disease and anticholinergic drug use.
Based on available evidence, however, pharmacists should warn older patients about chronic use of anticholinergic agents and other drugs that impair memory, including benzodiazepines and many other prescription drugs. Perhaps only the smallest effective anticholinergic drug dose should be used in older patients, if at all. Furthermore, these drugs should be discontinued if patients display signs of cognitive decline or memory impairment.
New shingles vaccine
Herpes zoster (shingles) results from the reactivation of latent varicella zoster virus in the dorsal-root or cranial-nerve ganglia, which typically occurs many years after primary infection. Shingles more commonly affects adults older than 50 years and those with immunocompromised states. A major complication of shingles is postherpetic neuralgia, which can result in chronic neuropathic pain. This complication is much more common in older patients.
A live-attenuated vaccine against herpes zoster (Zostavax—Merck) has been available in the United States for many years and is approved for adults aged 50 years or older. Its efficacy against herpes zoster, however, is significantly diminished in older patients, especially those older than 70 years. A recombinant subunit vaccine containing varicella zoster virus with a subunit antigen system—specifically glycoprotein E and the AS01B adjuvant system—is known as HZ/su. It has shown great promise in investigational studies against prevention of shingles in older patients.2
A pivotal clinical trial, known as Zoster Efficacy Study in Adults 50 Years of Age or Older (ZOE-50), demonstrated that two doses of HZ/su significantly lowered the risk for herpes zoster among adults aged 50 years and older.2 In this prospective clinical trial, subjects (n = 15,411) were stratified according to age group: 50–59 years, 60–69 years, and 70 years and older. Participants received either two intramuscular doses of HZ/su vaccine or placebo, separated by 2 months.
During the mean follow-up of 3.2 years, only 6 participants in the vaccine group developed herpes zoster, and 210 participants in the placebo group developed the disease. The overall efficacy of HZ/su against herpes zoster was between 96.6% and 97.9% for all age groups, with 97.2% efficacy overall. In contrast to previous clinical trials with live-attenuated herpes zoster, HZ/su vaccine efficacy did not diminish with age.
Injection site reactions, such as redness and swelling, were more common in the HZ/su group, relative to placebo. These reactions were graded severe in 9.5% of HZ/su recipients, compared with 0.4% of placebo recipients. It is unknown if this vaccine efficacy would wane over many years, or for how many years immunity is sustained, since the mean follow-up period in this study was 3.2 years. But the new vaccine holds particular promise as the population ages, given that more than 90% of adults are seropositive herpes varicella virus.2 An ongoing study, ZOE-70, which includes adults aged 70 years or older, will provide further assessment of HZ/su vaccine efficacy against postherpetic neuralgia and other complications of herpes zoster.
- JAMA Intern Med. 2015;175(3):401–7
- N Engl J Med. 2015;372(22):2087–96
- JAMA Intern Med. 2015;175(4):578–85