What’s new in treating older adults?
ABSTRACTClinical trials in the past few years have yielded findings that are relevant for clinical practice, not just for geriatricians but for all physicians who have elderly patients.
KEY POINTS
- Exercise has newly discovered benefits, such as preserving cognition and boosting the response to vaccination.
- Vitamin D supplementation has been found to prevent fractures, but yearly megadoses had the opposite effect.
- Denosumab (Prolia) has been approved for preventing fractures. It acts by inhibiting the receptor activator of nuclear factor kappa B (RANK) ligand.
- The outlook for elderly patients starting hemodialysis is bleak, with loss of function and a high risk of death.
- Dabigatran (Pradaxa), a direct thrombin inhibitor, may prove to be a safer alternative to warfarin (Coumadin).
- Cholinesterase inhibitors for Alzheimer disease are associated with higher risks of hospitalization for syncope, hip fractures, bradycardia, and pacemaker insertion.
- The Clinical Dementia Rating should be estimated when prescribing a cognitive enhancer and when advising a patient with memory impairment on driving safety.
- Delirium often accelerates dementia; interventions for hospitalized elderly patients may reduce its incidence.
DIALYSIS IN THE ELDERLY: A BLEAK STORY
KURELLA TAMURA M, COVINSKY KE, CHERTOW GM, YAFFE K, LANDEFELD CS, MCCOLLOCH CE. FUNCTIONAL STATUS OF ELDERLY ADULTS BEFORE AND AFTER INITIATION OF DIALYSIS. N ENGL J MED 2009; 361:1539–1547.
JASSAL SV, CHIU E, HLADUNEWITH M. LOSS OF INDEPENDENCE IN PATIENTS STARTING DIALYSIS AT 80 YEARS OF AGE OR OLDER (LETTER). N ENGL J MED 2009; 361:1612–1613.
Nursing home residents account for 4% of all patients in end-stage renal disease. However, the benefits of dialysis in older patients are uncertain. The mortality rate during the first year of dialysis is 35% in patients 70 years of age and older and 50% in patients 80 years and older.
Is dialysis helpful in the elderly, ie, does it improve survival and function?
Kurella Tamura et al11 retrospectively identified 3,702 nursing home residents starting dialysis in whom functional assessments had been done. The numbers told a bleak story. Initiation of dialysis was associated with a sharp decline in functional status, as reflected in an increase of 2.8 points on the 28-point Minimum Data Set–Activities of Daily Living (MDS-ADL) scale (the higher the score, the worse the function). MDS-ADL scores stabilized at a plateau for about 6 months and then continued to decline. Moreover, at 12 months, 58% of the patients had died.
The MDS-ADL score is based on seven components: eating, bed mobility, locomotion, transferring, toileting, hygiene, and dressing; function declined in all of these areas when patients started dialysis.
Patients were more likely to decline in activities of daily living after starting dialysis if they were older, were white, had cerebrovascular disease, had a diagnosis of dementia, were hospitalized at the start of dialysis, or had a serum albumin level lower than 3.5 g/dL.
The same thing happens to elders living in the community when they start dialysis. Jassal and colleagues12 reported that, of 97 community-dwelling patients (mean age 85), 46 (47%) were dead 2 years after starting dialysis. Although 76 (78%) had been living independently at the start of dialysis, only 11 (11%) were still doing so at 2 years.
Comment. These findings indicate that we do not know if hemodialysis improves survival. Hemodialysis may buy about 3 months of stable function, but it clearly does not restore function.
Is this the best we can do? Standard hemodialysis may have flaws, and nocturnal dialysis and peritoneal dialysis are used more in other countries. These dialysis techniques require more study in our older population. The lesson from these two publications on dialysis is that we should attend more carefully to slowing the decline in renal function before patients reach end-stage renal disease.
DABIGATRAN: AN ALTERNATIVE TO WARFARIN FOR ATRIAL FIBRILLATION
CONNOLLY SJ, EZEKOWITZ MD, YUSUF S, ET AL; RE-LY STEERING COMMITTEE AND INVESTIGATORS. DABIGATRAN VERSUS WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION. N ENGL J MED 2009; 361:1139–1151.
Atrial fibrillation is common, affecting 2.2 million adults. The median age of people who have atrial fibrillation is 75 years, and it is the most common arrhythmia in the elderly. Some 20% of ischemic strokes are attributed to it.13–15
Warfarin (Coumadin) is still the mainstay of treatment to prevent stroke in patients with atrial fibrillation. In an analysis of pooled data from five clinical trials,16 the relative risk reduction with warfarin was about 68% in the overall population (number needed to treat 32), 51% in people older than 75 years with no other risk factors (number needed to treat 56), and 85% in people older than 75 years with one or more risk factors (number needed to treat 15).
But warfarin carries a risk of bleeding, and its dose must be periodically adjusted on the basis of the international normalized ratio (INR) of the prothrombin time, so it carries a burden of laboratory monitoring. It is less safe in people who eat erratically, resulting in wide fluctuations in the INR.
Dabigatran (Pradaxa), a direct thrombin inhibitor, is expected to become an alternative to warfarin. It has been approved in Europe but not yet in the United States.
Connolly et al,17 in a randomized, double-blind trial, assigned 18,113 patients who had atrial fibrillation to receive either dabigatran 110 or 150 mg twice daily or adjusted-dose warfarin in an unblinded fashion. At 2 years, the rates of stroke and systemic embolism were about the same with dabigatran 110 mg as with warfarin but were lower with dabigatran 150 mg (relative risk 0.66, 95% confidence interval [CI] 0.53–0.82, P < .001). The rate of major bleeding was lower with dabigatran 110 mg than with warfarin (2.71% per year vs 3.36% per year, P = .003), but it was similar with dabigatran 150 mg (3.11% per year). Rates of life-threatening bleeding were 1.80% with warfarin, 1.22% with dabigatran 110 mg (P < .05), and 1.45% with dabigatran 150 mg (P < .05).
Comment. I suspect that warfarin’s days are numbered. Dabigatran 110 or 150 mg was as safe and as effective as warfarin in clinical trials, and probably will be more effective than warfarin in clinical practice. It will also probably be safer than warfarin in clinical practice, particularly in challenging settings such as long-term care. On the other hand, it will likely be much more expensive than warfarin.
DEMENTIA
Adverse effects of cholinesterase inhibitors
GILL SS, ANDERSON GM, FISCHER HD, ET AL. SYNCOPE AND ITS CONSEQUENCES IN PATIENTS WITH DEMENTIA RECEIVING CHOLINESTERASE INHIBITORS: A POPULATION-BASED COHORT STUDY. ARCH INTERN MED 2009; 169:867–873.
Cholinesterase inhibitors, eg, donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon), are commonly used to treat Alzheimer disease. However, these drugs carry risks of serious adverse effects.
Gill et al18 retrospectively reviewed a database from Ontario, Canada, and identified about 20,000 community-dwelling elderly persons admitted to the hospital who had been prescribed cholinesterase inhibitors and about three times as many matched controls.
Several adverse events were more frequent in people receiving cholinesterase inhibitors. Findings (events per 1,000 person-years):
- Hospital visits for syncope: 31.5 vs 18.6, adjusted hazard ratio (HR) 1.76, 95% CI 1.57–1.98
- Hip fractures: 22.4 vs 19.8, HR 1.18, 85% CI 1.04–1.34
- Hospital visits for bradycardia: 6.9 vs 4.4, HR 1.69, 95% CI 1.32–2.15
- Permanent pacemaker insertion: 4.7 vs 3.3, HR 1.49, 95% CI 1.12–2.00.
Comment. This study adds to the concerns that cholinesterase inhibitors, which have only modest cognitive benefits, may increase the risk of falls, injury, and need for pacemaker placement in demented patients. A low threshold to stop medications in this class should be considered when a patient on a cholinesterase inhibitor presents with bradycardia, falls, and syncope.
