Geriatrics update 2012: What parts of our practice to change, what to ‘think about’
ABSTRACTMany new guidelines and studies of interest to the geriatric population have emerged in the areas of falls and fracture prevention, cardiovascular care, depression, and Alzheimer disease. Some of these guidelines and studies translate to immediate changes that should be made to clinical practice; others are new areas of controversy.
KEY POINTS
- To prevent falls, patients should be asked not only about recent falls but about balance. Referral for a multicomponent falls evaluation should be considered.
- For patients age 80 and older, a target systolic blood pressure of 140 to 145 mm Hg is acceptable, and blood pressure below 130 mm Hg systolic and 65 mm Hg diastolic should be avoided.
- The dosage of the antidepressant citalopram (Celexa) should not exceed 40 mg per day in the general population and 20 mg in patients age 60 and older.
- Calcium supplementation may increase the risk of myocardial infarction and stroke. A large annual dose of vitamin D appears harmful, raising questions about the long-term safety of large doses given weekly or monthly.
BISPHOSPHONATES AND NONTRAUMATIC THICK BONE FRACTURES
Bisphosphonates have been regarded as the best drugs for preventing hip fracture. But in 2010, the US Food and Drug Administration (FDA) issued a warning that bisphosphonates have been associated with “atypical” femoral fractures. The atypical fracture pattern is a clean break through the thick bone of the shaft that occurs after minimal or no trauma.5 This pattern contrasts with the splintering “typical” fracture in the proximal femur in osteoporotic bone, usually after a fall.
Another characteristic of the atypical fractures is a higher incidence of postoperative complications requiring revision surgery. In more than 14,000 women in secondary analyses of three large randomized bisphosphonate trials, 12 fractures in 10 patients were found that were classified as atypical, averaging to an incidence of 2.3 per 10,000 patient-years.6
A population-based, nested case-control study7 using Canadian pharmacy records evaluated more than 200,000 women at least 68 years old who received bisphosphonate therapy. Of these, 716 (0.35%) sustained an atypical femoral fracture and 9,723 (4.7%) had a typical osteoporotic femoral fracture. Comparing the duration of bisphosphonate use between the two groups, the authors found that the risk of an atypical fracture increased with years of usage (at 5 years or more, the adjusted odds ratio was 2.74, 95% CI 1.25–6.02), but the risk of a typical fracture decreased (at 5 years or more, the adjusted odds ratio was 0.76, 95% CI 0.63–0.93). The study suggests that for every 100 hip fractures that bisphosphonate therapy prevents, it causes one atypical hip fracture.
Comments. These studies have caused some experts to advocate periodic bisphosphonate “vacations,”8 but for how long remains an open question because the risk of a typical fracture will increase. It is possible that a biomarker can help establish the best course, but that has yet to be determined.
DENOSUMAB: A NEW DRUG FOR OSTEOPOROSIS WITH A BIG PRICE TAG
Denosumab (Prolia, Xgeva), a newly available injectable drug, is a monoclonal antibody member of the tumor necrosis factor super-family.9 It is FDA-approved for osteoporosis in postmenopausal women at a dosage of 60 mg every 6 months and for skeletal metastases from solid tumors (120 mg every 4 weeks). It is also being used off-label for skeletal protection in women taking aromatase inhibitors and for men with androgen deficiency.
This drug is expensive, costing $850 per 60-mg dose wholesale, and no data are yet available on its long-term effects.
Since the drug is not cleared via renal mechanisms, there is some hope that it can be used to treat osteoporosis in patients with advanced chronic kidney disease, since bisphosphonates are contraindicated in those with an estimated glomerular filtration rate (GFR) less than 30 to 35 mL/min. However, the major study of denosumab to date, the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, had no patients with stage 5 chronic kidney disease (GFR < 15 mL/min/1.73 m2 or on dialysis), and too few with stage 4 chronic kidney disease (GFR 15–29) to demonstrate either the safety or efficacy of denosumab in patients with advanced chronic kidney disease.10
HYPERTENSION TREATMENT
A secondary analysis of a recent large hypertension study confirmed the benefits of antihypertensive therapy in very old adults and suggested new targets for systolic and diastolic blood pressures.11,12
The Systolic Hypertension in the Elderly Program (SHEP) trial,13 the Systolic Hypertension in Europe (Syst-Eur) trial,14 and the Hypertension in the Very Elderly Trial (HYVET)15 are the major, randomized, placebo-controlled antihypertensive trials in older adults. They all showed a reduction in the risk of stroke and cardiovascular events. The diuretic studies (SHEP and HYVET)13,15 also showed a lower risk of heart failure and death.
Most recently, secondary analysis of the International Verapamil-Trandolapril (INVEST) study11,12 showed that adults in the oldest groups (age 70–79 and 80 and older), experienced a greater risk of adverse cardiovascular outcomes if systolic blood pressure was lowered to below about 130 mm Hg. As diastolic blood pressure was lowered to about the 65–70 mm Hg range, all age groups in the study experienced an increased risk of cardiovascular events. These results confirm the findings of a secondary analysis of the SHEP trial,16 showing an increased risk of cardiovascular events when diastolic pressure was lowered to below approximately 65 mm Hg.
These studies have been incorporated into 75 pages of the 2011 Expert Consensus Document on Hypertension in the Elderly issued by the American College of Cardiology Foundation and the American Heart Association.17 In a nutshell, the guidelines suggest that older adults less than 80 years of age be treated comparably to middle-aged adults. However, for adults age 80 and older:
- A target for systolic blood pressure of 140 to 145 mm Hg “can be acceptable.”
- Initiating treatment with monotherapy (with a low-dose thiazide, calcium channel blocker, or renin-angiotensin-aldosterone system drug) is reasonable. A second drug may be added if needed.
- Patients should be monitored for “excessive” orthostasis.
- Systolic blood pressure lower than 130 mm Hg and diastolic blood pressure lower than 65 mm Hg should be avoided.
TRANSCATHETER AORTIC VALVE IMPLANTATION APPROVED BY THE FDA
An estimated 2% to 9% of the elderly have aortic stenosis. Aortic valve replacement reduces mortality rates and improves function in all age groups, including octogenarians. Those with asymptomatic aortic stenosis tend to decline very quickly once they develop heart failure, syncope, or angina. Aortic valve replacement has been shown to put people back on the course they were on before they became symptomatic.
Transcatheter self-expanding transaortic valve implantation was approved by the FDA in November 2011. The procedure does not require open surgery and involves angioplasty of the old valve, with the new valve being passed into place through a catheter and expanded. Access is either transfemoral or transapical.
Transaortic valve implantation has been rapidly adopted in Europe since 2002 without any randomized control trials. The Placement of Aortic Transcatheter Valves (PARTNER) trial18 in 2011 was the first randomized trial of this therapy. It was conducted at 25 centers, with nearly 700 patients with severe aortic stenosis randomized to undergo either transcatheter aortic valve replacement with a balloon-expandable valve (244 via the transfemoral and 104 via the transapical approach) or surgical replacement. The mean age of the patients was 84 years, and the Society of Thoracic Surgeons mean score was 12%, indicating high perioperative risk.
At 30 days after the procedure, the rates of death were 3.4% with transcatheter implantation and 6.5% with surgical replacement (P = .07). At 1 year, the rates were 24.2% and 26.8%, respectively (P = 0.44, and P = .001 for noninferiority). However, the rate of major stroke was higher in the transcatheter implantation group: 3.8% vs 2.1% in the surgical group (P = .20) at 1 month and 5.1% vs 2.4% (P = .07) at 1 year. Vascular complications were significantly more frequent in the transcatheter implantation group, and the new onset of atrial fibrillation and major bleeding were significantly higher in the surgical group.
Patients in the transcatheter implantation group had a significantly shorter length of stay in the intensive care unit and a shorter index hospitalization. At 30 days, the transcatheter group also had a significant improvement in New York Heart Association functional status and a better 6-minute walk performance, although at 1 year, these measures were similar between the two groups and were greatly improved over baseline. Quality of life, measured using the Kansas City Cardiomyopathy Questionnaire, was higher both at 6 months and at 1 year in the transcatheter implantation group compared with those who underwent the open surgical procedure.19
Comments. The higher risk of stroke with the transcatheter implantation procedure remains a concern. More evaluation is also needed with respect to function and cognition in the very elderly, and of efficacy and safety in higher- and lower-risk patients.
