American Geriatrics Society Annual Meeting, Chicago, IL, April 29-May 2, 2009

American Society of Consultant Pharmacists Midyear Conference, May 7-9, 2009

POSTER

Osteoporosis, Congestive Heart Failure, and Parkinson’s Disease

Chicago, IL—In their efforts to ascertain whether a relationship between osteoporosis and congestive heart failure (CHF) exists, researchers from the University of Puerto Rico School of Medicine, San Juan, and Johns Hopkins University, Baltimore, MD, at the AGS Annual Meeting, concluded that women who do not have CHF are less likely to develop osteoporosis because of the lack of calcium demand for compensatory mechanisms required by the heart. A healthy vitamin D status also contributes to this effect.

It is known that CHF leads to inefficient heart pumping. In order to compensate, the heart will increase its rate or pump with a greater force; both methods require calcium in order to be effective. Since the calcium demand may be increased in both processes, the body may rely on greater bone resorption in order to obtain this mineral. This, in turn, may lead to lower bone mass density and more susceptibility to fractures; these measures can worsen CHF.

To assess the relationship between osteoporosis and CHF, investigators used logistic regression in a cross-sectional analysis of the Women’s Health and Aging I sample population (n=1002), after adjusting for race, history of smoking, myocardial infarction, cholesterol, body mass index, medications, diabetes mellitus, income, hypertension, vitamin D, and CHF. Osteoporosis and CHF were defined on the basis of adjudicated data, standardized clinical algorithms, medical record review, objective data, and self-report reviewed by trained clinicians to adjudicate whether disease was present. The regression analysis showed that the odds of developing osteoporosis increased by 39% (95% confidence interval [CI], 1.25-1.55; P < 0.05) in women with smoking history.

Females with high cholesterol were 33% (95% CI, 1.17-1.54; P < 0.05) more likely to have osteoporosis, along with a 26% (95% CI, 1.14-1.41; P < 0.05) increase in those with hypertension. Women who did not have CHF were 18% (95% CI, 0.72-0.92; P < 0.05) less likely to develop osteoporosis, and those who had adequate vitamin D levels decreased their risk by 18% (95% CI, 0.72-0.92; P < 0.05). Researchers presenting this poster session concluded that the implications of this study include generating a better assessment of the connection existing between CHF and osteoporosis. In so doing, physicians can provide their patients with more accurate and complete information regarding both diseases, thereby reducing the amount of patients who may feel uninformed about these impairments.

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In other osteoporosis research presented at the AGS meeting, investigators reported that there is considerable room for improvement in the prescribing of bone prophylaxis in patients with Parkinson’s disease (PD) who are at risk of falling or with risk factors for osteoporosis (OP). Researchers from the University of Cambridge and Addenbrooke’s Hospital, Cambridge, UK, undertook an audit to assess the quality of bone prophylaxis prescribing in patients with bilateral symptoms of PD. Patients with PD are at risk of falling, and thus of fracture, and the likelihood of fracture will be highest in those with bilateral symptoms who often have multiple risk factors for OP.

The notes of 98 patients attending PD clinics, or having an inpatient admission, who were identified with bilateral PD were screened for falls, fractures, OP risk factors, and prescription of bone prophylaxis. Significant risk of OP was defined as having three or more of the following: postmenopausal female, breast cancer, current smoker, reduced weight bearing, nutritional deficiency, reduced sunlight exposure, body mass index less than 19 kg/m2, hyperthyroidism, family history, low testosterone in men, alcohol consumption of more than 3 units per day, and medications (long-term steroids, thyroxine, selective serotonin reuptake inhibitors, heparin, methotrexate, antiepileptics, aluminium-containing antacids, aromatase inhibitors, and diuretics).

Results revealed that 54% of patients with PD were appropriately prescribed bone prophylaxis. In addition, 46% of patients with PD received bone prophylaxis following a fracture, and 17% on long-term oral steroids and none with concomitant rheumatoid arthritis received appropriate bone prophylaxis. Sixty-two percent of patients with PD who had significant risk factors for OP were treated with calcium and vitamin D. Finally, 100% of patients with OP confirmed by DEXA scan were prescribed bone prophylaxis. Researchers concluded that the multidisciplinary Parkinson’s team should pay more attention to the importance of bone health, improve their assessment of falls and OP risk, and be more assiduous in their prescribing of bone prophylaxis. In addition, they hope that implementation of these recommendations will help to reduce the risk of a patient with bilateral PD sustaining a fracture following a fall.

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Modern Management of Gout

Chicago, IL—The goals of treatment for chronic gout are to maintain serum urate of 6 mg/dL or lower, monitor serum urate to ensure appropriate levels are achieved/maintained, suppress gout flares triggered by serum urate lowering by continuing acute gout prophylaxis for 6 months, and recognize and treat associated comorbidities, according to Naomi Schlesinger, MD, Chief, Division of Rheumatology, Associate Professor of Medicine, UMDNJ/Robert Wood Johnson Medical School, New Brunswick, NJ, at the AGS Annual Meeting. Nonpharmacologic modalities and preventive measures include rest of affected joint for 1-2 days and topical ice treatment during acute gout attacks. She discussed diet-related factors as increasing risk of gout, and said that foods that may decrease risk of gout include low meat and seafood consumption, high dairy consumption, and high coffee consumption.

Pharmacologic treatment goals for gout include: terminating the acute attack as rapidly as possible; protecting against further attacks (use prophylaxis); and treating the hyperuricemia, preventing disease progression, and treating comorbidities (provide long-term correction of the metabolic problem, lower the serum urate so as to deplete the total body uric acid pool). Termination/resolution of the acute attack involves controlling crystal-induced inflammation and pain (not a cure for gout, as it only resolves the symptoms and urate crystals remain in the joint); medication options include nonsteroidal anti-inflammatory drugs (NSAIDs), oral colchicine, corticosteroids, and ACTH. The critical issues are rapid initiation of therapy, adequate dosing, and appropriate duration of therapy. In patients without complications, NSAIDs are the preferred therapy unless there are contraindications to their use. FDA-approved drugs for gout are indomethacin, naproxen, and sulindac. Studies have not shown which NSAID works better. Oral and IV colchicine were “grandfathered” before the 1969 FDA phase III trials for drug toxicity became law. Data on toxic reactions are therefore based on passive surveillance. Colchicine toxicity due to IV colchicine has been compared to arsenic poisoning.

Prophylactic options are low-dose oral colchicine and NSAIDs. The speaker recommended that these agents be initiated when starting urate-lowering therapy for at least 6 months. In a 2005 study by Becker et al in the New England Journal of Medicine examining the incidence of gout flares during urate-lowering therapy, the speaker said that 70% experienced flares during the trial. In another study by Borstad et al published in 2004 in Journal of Rheumatology, colchicine prophylaxis was proven useful when initiating urate-lowering therapy. During 6 months of follow-up, gout flares occurred in 33% of colchicine patients and in 77% of placebo patients (P < 0.05). Colchicine prophylaxis during allopurinol initiation reduced frequency and severity of flares.

The goals of treating hyperuricemia and preventing disease progression are to improve patient and physician understanding through education, lower serum urate to ≤ 6.0 mg/dL to allow depletion of total body urate pool, and to achieve appropriate urate levels without drug toxicity. Therapy should be lifelong, as intermittent therapy or withdrawal of agents leads to recurrence of acute attacks, tophi, etc. Urate-lowering drugs include uricostatic drugs (xanthine oxidase inhibitors, which decrease UA synthesis [allopurinol, febuxostat, and oxypurinol]), uricosuric drugs (inhibit UA reabsorption proximal tubule [probenecid, sulphinpyrazone, benzbromarone, losartan, and fenofibrate]), and uricolytic drugs (uricase: catalyzes conversion UA into allantoin). Some limitations to allopurinol are if renal function is an issue, multiple drug interactions, target serum urate not always achieved, potentially fatal hypersensitivity syndrome, and nonselective enzyme inhibition; and to uricosurics are if renal function is an issue, multiple drug interactions, target serum urate not always achieved, risk of nephrolithiasis, and multiple doses daily required. The speaker stated that febuxostat is the first drug on the market since about 1960, when allopurinol went on the market. It is a specific inhibitor of xanthine oxidase, and has been found to significantly reduce SU as compared to placebo; dose adjustments are not necessary in mild and moderate CKD (stages 2 and 3). In the FACT study by Becker et al in 2005 in New England Journal of Medicine, it was found that allopurinol 300 mg/day, febuxostat 80 mg/day, and febuxostat 120 mg/day all had similarly reported adverse events (any treatment-emergent event, any serious adverse event, any treatment-related adverse event, and deaths).

Regarding treating the hyperuricemia and preventing disease progression, the speaker stated the importance of patient follow-up; serum urate needs to be monitored to assure that a target level of less than 6.0 mg/dL is achieved (monitor SU every 4-6 wk after initiating urate-lowering therapy until levels reach < 6.0 mg/dL, and continue to monitor every 6-12 mo after target SU is achieved). Assess for any adverse reactions to the drug used. Some therapeutic challenges in the elderly are that serum urate is not always lowered to ≤ 6.0 mg/dL, and treatment gaps exist in patients with renal insufficiency, allergies/allopurinol intolerance (not uncommon), and drug interactions/adverse drug reactions (common).

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Managing Anemia Associated with Chronic Renal Failure

Orlando, FL—Chronic kidney disease (CKD) has been described by various terms such as chronic renal failure, early renal insufficiency, chronic renal insufficiency, pre-dialysis, and pre-endstage renal disease. Tommy Philpot, PharmD, GCP, FASCP, spoke about CKD at the American Association of Consultant Pharmacists Midyear Meeting and highlighted the National Kidney Foundation (NKF) recommendations, which include using glomerular filtration rate (GFR) to measure the level of kidney function and stage of disease. The Modification of Diet in Renal Disease test is the recommended test to determine kidney function. The NKF, American Diabetes Association, and American Heart Association recommend annual checks of GFR.

Both the incidence and prevalence of CKD are rising in the U.S., and age-related impairment is common in elderly residents of long-term care (LTC) facilities, with approximately 44% of residents with the disease. Dr. Philpot discussed that serum creatinine alone is not reliable for CKD diagnosis. He said that risk factors for the disease include diabetes, hypertension, age, family history of kidney disease or diabetes, and male gender. He outlined the 5 stages of CKD and the recommended clinical actions for each (www.kidney.org), and discussed how LTC residents die of complications of CKD, such as anemia, cardiovascular disease, malnutrition, neuropathy, bone disease, and decline in functioning and well being. The World Health Organization defines anemia as hemoglobin less than 13.0 g/dL in adult men and less than 12 g/dL in adult women; the NKF defines anemia as less than 13.5 g/dL in men and less than 12 g/dL in women. Anemia prevalence in the LTC setting results from several studies (Carmel, Salive et al, Artz et al, and Van Vleet et al for the RESTORE study).

Erythropoietin deficiency is the main causal factor of anemia of CKD. Epoetin alfa is indicated for the treatment of anemia associated with chronic renal failure, including patients on dialysis and those not on dialysis. It is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients. Blood pressure should be adequately controlled and the patient’s iron stores should be evaluated (transferrin saturation should be at least 20% and ferritin at least 100 ng/mL) prior to initiation of therapy. Epoetin alfa is not intended for patients who require immediate correction of severe anemia, and it may obviate the need for transfusions, but is not a substitute for emergency transfusions (see full prescribing information).

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Opioid-Induced Constipation in Advanced Illness

Orlando, FL—Opioid-induced constipation is an important problem for patients with advanced illness and poses therapeutic challenges for clinicians.

Tom Snader, PharmD, CGP, FASCP, discussed treatment of this problem in patients receiving palliative care, when response to laxative therapy has not been sufficient. He cited a study published in The New England Journal of Medicine by Thomas and colleagues that examined the use of methylnaltrexone, a mu-opioid-receptor antagonist, in 134 patients with advanced illness who had received opioids for 2 or more weeks, and who had received stable doses of opioids and laxatives for 3 or more days without relief of constipation. They were randomly assigned to receive subcutaneous methylnaltrexone at a dose of 0.15 mg per kilogram of body weight or placebo every other day for 2 weeks. Coprimary outcomes were laxation within 4 hours after the first dose of the study drug, and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial.

In the methylnaltrexone group, 48% of patients had laxation within 4 hours after the first study dose, as compared with 16% in the placebo group, and 52% had laxation without the use of a rescue laxative within 4 hours after two or more of the first four doses, as compared with 9% in the placebo group (P = 0.0001 for both comparisons). The response rate remained consistent throughout the extension trial. The median time to laxation was significantly shorter in the methylnaltrexone group than in the placebo group. Evidence of withdrawal mediated by central nervous system opioid receptors or changes in pain scores was not observed. The investigators concluded that subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal.

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Chronic Obstructive Pulmonary Disease in LTC

Orlando, FL—Chronic obstructive pulmonary disease (COPD) is a significant challenge in long-term care (LTC) and is becoming a growing health burden. Many patients in LTC facilities are admitted post-stroke or post-hip fracture and find out they have COPD. It is not high on the radar screen for diagnosis and assessment, and therefore is underrecognized. COPD is the fourth most prevalent disorder in LTC—almost the same as stroke—and will likely move up in prevalence.

At the American Society of Consul-tant Pharmacists Midyear Meeting, Tom Snader, PharmD, CGP, FASCP, pointed out the American Medical Directors Association (AMDA) clinical guidelines for COPD. He discussed the clinical course of COPD that includes sputum production and chronic cough, shortness of breath, increased fatigue, low birth weight, history of smoking, frequent respiratory infections, and history of exposure to environmental factors, and highlighted the importance of preventing or slowing the progression of the disease. He pointed out the need to confirm the diagnosis by spirometry, and the importance of LTC facilities purchasing a handheld spirometer. Dr. Snader discussed the 3 stages of COPD in the AMDA classification, as well as the American Thoracic Society and GOLD guidelines’ 4 stages.

The goal of pharmacologic therapy for COPD is to reduce inflammation and exacerbations and the decline in FEV1 lung capacity. Dr. Snader discussed use of a twice-daily dry powder inhaler (DPI) delivery system in LTC settings and its ease of use as compared with a metered-dose inhaler (MDI). “If a patient can suck in water from a straw upon request, he or she can inhale from a DPI,” said the speaker. “With an MDI, the patient cannot always be observed to know whether it’s being done correctly. With an MDI, 90% of the drug can get swallowed, and four times a day dosing is too much.”

The speaker discussed the difference between asthma, for which a long-acting bronchodilator is preferred in reducing acute exacerbations, and COPD. For COPD, the speaker recommended a long-acting inhaled anticholinergic bronchodilator agent such as ipratropium or tiotropium. Dr. Snader cited a 1-year clinical trial that compared ipratropium and tiotropium, and found a 25 mL improvement with tiotropium in air exhalation due to reduced air trapping that can lead to dyspnea, and no decline in FEV1 for 1 year. Tiotropium is the only long-acting anticholinergic bronchodilator indicated for long-term once-daily maintenance treatment of bronchospasm associated with COPD. Patients with greater air capacity often will eat better and participate more in exercise, thereby improving their quality of life.

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Major Depressive Disorder and Generalized Anxiety Disorder in LTC

Orlando, FL—Roger Cadieux, MD, defined depression as a genetically predisposed, biochemically mediated, chronic and recurring illness, one that causes older persons embarrassment that leads to refusal to take medication. If left untreated, it can last 6 months or more. Treatment can be successful in 4-6 weeks and should never be discontinued in elderly patients since there’s a 70% chance it will recur with cessation of treatment. He cited the National Institutes of Health guidelines for treatment of older persons with depression that recommends lifelong treatment.

To soften the stigma that often accompanies depression in the elderly, Dr. Cadieux said that he doesn’t focus on the depression diagnosis with these patients, but rather tells them that antidepressant treatment can also help with the multiple chronic complaints that they have that can accompany and contribute to the “sadness” (eg, diabetes, angina, asthma).

The speaker pointed out that only four agents are approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD), but cautioned that they are not interchangeable in the elderly; some have been shown to create more anxiety or to cause more side effects such as nausea and vomiting. He discussed several studies that looked at their efficacy in the elderly population. He cited a study by Wade et al in which escitalopram, a selective serotonin reuptake inhibitor (SSRI), was compared to placebo in patients with MDD (DSM-IV) who had baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores ≥22 and ≤40. After a 1-week, single-blind placebo period, patients were randomized to receive escitalopram 10 mg/day (n =191) or placebo (n =189) in an 8-week, double-blind period. The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 (last observation carried forward, LOCF) of 2.7 points (SE 0.85; P = 0.002). In further by-week efficacy analyses, the effect of escitalopram was consistently larger than that of placebo (P < 0.05) beginning at week 1 (Clinical Global Impression-Improvement score), week 2 (MADRS score), or week 3 (Clinical Global Impression-Severity score). Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo. Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients, although it was infrequent and transient.