American Society of Consultant Pharmacists 40th Annual Meeting
Anaheim, CA; November 18-20, 2009

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Functional Communication in Alzheimer’s Disease in LTC

Anaheim, CA—Alzheimer’s disease (AD) can profoundly affect communication skills of frail elderly residents in LTC settings. Dr. Richard Stefanacci, Director of the Institute for Geriatric Studies at the Mayes College of Healthcare Business & Policy, University of the Sciences, Philadelphia, PA, and medical director of NewCourtland LIFE, spoke at the American Society of Consultant Pharmacists meeting about the importance of enhancing quality of life (QoL) through improved communication, which in turn benefits residents, their families, and facility staff.

Functional communication assessment is required to be done 14 days after nursing home admission as a result of OBRA ‘87. Further, the new MDS 3.0—now delayed until October 2010—will include a detailed section on cognitive impairment, as well as a requirement for resident interviews. This is in keeping with a focus on outcomes, especially regarding quality of life. The push is toward MDS truly driving the care plan for better outcomes, which provides opportunities for consultant pharmacists to carve out an important niche.

For mild AD, cholinesterase inhibitors are the recommended line of treatment showing efficacy. Unfortunately, in the nursing home, many residents enter the facility not receiving any treatment despite having moderate to severe AD. The speaker emphasized that these patients often benefit from combination therapy. He cited several studies (including Cummings et al, Neurology, 2006; Tariot et al, JAMA, 2004; Reisbert, N Engl J Med, 2003; Arch Neurol, 2006; Winblad et al, J Geriatr Psychiatry, 1999) that showed the efficacy of memantine for treatment of moderate to severe AD, especially in combination with cholinesterase inhibitors. New data on combination therapy with memantine and donepezil show that it improves communication in persons with AD when titrated to therapeutic doses. Tariot et al (JAMA, 2004) looked at persons already receiving the acetylcholinesterase inhibitor (AChEI) donepezil for 2 years who had memantine added to their regimen. The study focused on four areas—cognition, function (ADL, IADL), behavior, and communication—and assessed reading and writing skills. Residents were asked to respond to verbal cueing. Results showed that the combination therapy demonstrated efficacy in ADL, improved behavior, and delayed the onset of behavioral symptoms.

Another study (Hofbauer, presented at the 12th International Conference on Alzheimer’s Disease; July 11-16, 2009; Vienna, Austria) was a 12-week evaluation of function communications and looked at 10 domains: Greeting/Naming, Answering Questions, Writing, Comprehension of Signs and Object-to-Picture Matching, Word Reading and Comprehension, Reminiscing, Following Commands, Pantomime, Gesture, Conversation.

Another measure was to focus on four domains: social communication, communication of basic needs, reading/writing numbers and concepts, and daily planning, which demonstrated improvement in functional communication with memantine over placebo.

Dosing of medication for moderate and severe AD is a significant issue in LTC; many healthcare providers are not titrating up enough, so residents are receiving subtherapeutic doses. Healthcare providers need to start patients on medications such as memantine at 5 mg and go up to 10 mg twice daily for the therapeutic dose. The only individuals for whom it is contraindicated are those with severe renal impairment.

Dr. Stefanacci revealed how AD is often a “seasonal diagnosis,” with the most common time for diagnosing persons with AD occurring immediately after the winter holidays, when families often get together to celebrate, and members notice changes in their parents’ and other older members’ behavior, which can include bills piling up in their homes. Increasingly many persons with AD are able to mask their disease through use of modern technology—GPS systems in their cars, handheld memory-jogging devices, and other methods of reminding themselves—which makes it more difficult for clinicians to detect common signs of forgetfulness.

Dr. Stefanacci emphasized that having a caregiver present at assessments as well as completing pill counts is vital to determine medication adherence, especially since elderly persons with AD often are not honest about adherence to their medications. Nonadherence is a major problem, with many individuals not filling prescriptions, decreasing their dosing, missing doses, or even stopping taking their medications. These patients can benefit from supervised administration to ensure adherence. In closing, the speaker discussed the coming healthcare reform changes that will focus on outcomes, thus increasing the need for improved adherence. Alzheimer’s disease was used as an example where these improvements in management could result in better outcomes for all involved.

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Prediabetes in a Nursing Home Patient with Renal Insufficiency

Anaheim, CA—Prediabetes is a common condition found in elderly persons, so the question is, should we be more proactive in treating prediabetes in the nursing home? Laura Shane-McWhorter, PharmD, Clinical Professor, University of Utah College of Pharmacy, spoke about diabetes mellitus (DM) in the elderly at a symposium held during the American Society of Consultant Pharmacists meeting. She discussed the conservative guidelines from the American College of Endocrinology and the American Association of Clinical Endocrinologists (ACE/AACE) for diagnosing prediabetes: impaired fasting glucose (IFG) of 100-125 mg/dL; impaired glucose tolerance (IGT) of 140-199 mg/dL; both IFG and IGT; and metabolic syndrome (prediabetes equivalent). Metabolic risk factors include abdominal obesity, triglycerides of 150 mg/dL or greater, high-density lipoprotein cholesterol of less than 40 mg/dL in men and less than 50 mg/dL in women, blood pressure of 130/85 mm Hg or greater or taking blood pressure medication, and fasting blood glucose (FBG) of 100 mg/dL or greater.

Dr. Shane-McWhorter discussed the NHANES III study and pointed out that 24% of Americans have metabolic syndrome, with the prevalence increasing with age. According to the guidelines, the most appropriate initial management is lifestyle management: improve diet (eg, increase fiber, decrease salt intake, reduce calorie intake), decrease body weight by 5-10%, increase physical activity, smoking cessation, lower lipids to the appropriate target with a variety of medications (with statins, fibrates, colesevelam, ezetimibe, aspirin, among others), lower blood pressure to appropriate target (with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, non-dihydropyridine calcium-channel blockers, among others), and use pharmacologic glycemia treatment in high-risk patients.

The speaker discussed the Diabetes Prevention Program (DPP), which had four arms (the medication in the fourth arm, troglitazone, was taken off the market) and looked at lifestyle versus placebo, metformin versus placebo, and lifestyle versus metformin. Investigators found that metformin was not as effective in older individuals, those with lower body mass index, or those with higher FPG or postprandial glucose. Weight loss due to exercise and diet was the strongest predictor in reduction of risk: for every 1-kg loss of weight there was a 16% risk reduction for DM (Knowler et al, N Engl J Med, 2002; Hamman et al, Diabetes Care, 2006). The DPP study was stopped early because of benefits found. The STOP-NIDDM (acarbose vs placebo; Chiasson et al, Lancet, 2002) study reported that acarbose decreased progression to DM by 25%, regardless of age, and decreased cardiovascular events, but was difficult to tolerate.

Looking at the glitazones as a therapeutic option, the DREAM study (rosiglitazone vs placebo; Gerstein et al, Lancet, 2006) showed decreased progression to DM or death by 62%. The ACT NOW study showed decreased progression to DM and possible preservation of beta cell function. Problems included risk of heart failure and other adverse events. Regarding use of incretins, which may preserve beta cell function and have beneficial effects on insulin secretion, long-term trials are needed to evaluate efficacy and safety in prediabetes.

For patients with prediabetes, the speaker concluded by recommending annual monitoring of FPG and A1C, albumin/creatinine, fasting lipids, and blood pressure. In general, high-risk patients with more than one factor (IFG, IGT, or metabolic syndrome) should be monitored more frequently. Risk reduction is key, with prevention and lifestyle management the major intervention, and pharmacologic management utilized when needed.

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POSTERS

Drug Utilization and Cost for Erythropoiesis-Stimulating Agents in a LTC Population with Chronic Kidney Disease

Anaheim, CA—In a poster presented at the annual ASCP meeting comparing drug utilization patterns and costs in LTC patients with chronic kidney disease (CKD) not on dialysis receiving epoetin alfa (EPO) or darbepoetin alfa (DARB), researchers reported a 42% higher drug cost with DARB as compared with EPO and a dose ratio of 273:1 (Units EPO: mcg DARB). AnalytiCare Long-Term Care database was used to conduct an analysis of pharmacy prescription claims from January 2007 through March 2009. Patients age 18 years or older, with one or more EPO or DARB pharmacy claims were included; persons diagnosed with cancer, receiving chemotherapy or radiation therapy, receiving renal dialysis, or receiving both agents were excluded from the study. Mean cumulative erythropoiesis-stimulating agent (ESA) dose was used to calculate drug cost (based on April 2009 wholesale acquisition cost) and dose ratio (Units EPO: mcg DARB).

Researchers identified a total of 2259 ESA-treated patients (EPO 1640; DARB 619). Patients taking EPO were slightly older (76.1 vs 74.8, P = -0.021) as compared with patients taking DARB. The education level, race distribution, and proportion of women were similar between groups. In addition, the mean days supply per prescription and number of prescriptions per patient were similar (days supply: 11.0 vs 11.5; number of prescriptions: 3.3 vs 3.4, P > 0.05 for both). Results showed that the mean [SD] cumulative dose was 98,420 [122,381] Units for EPO and 360 [428] mcg for DARB, resulting in a dose ratio of 273:1 (Units EPO: mcg DARB). The corresponding drug cost was 42% higher with DARB than with EPO ($1734 vs $1217, P < 0.001).

This study was funded by Centocor Ortho Biotech Services, LLC.

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Drug Utilization and Cost Considerations in Elderly CKD Patients Receiving Erythropoiesis-Stimulating Agents Through Pharmacy Claims

Anaheim, CA—In another poster presented at the annual ASCP meeting, the same researchers compared drug utilization and costs through pharmacy claims in elderly patients with CKD not on dialysis receiving EPO or DARB. The study concluded that elderly patients with CKD receiving ESAs through pharmacy benefits reported 27% higher drug cost with DARB as compared with EPO and a dose ratio of 276:1. Researchers conducted an analysis of pharmacy claims from July 2002 through June 2008 using the Ingenix IMPACT database. Patients age 65 years or older, newly initiated on EPO/DARB with one or more ESA pharmacy claims, and one or more CKD claims within 90 days prior to their first prescription were included; those receiving ESA in the medical setting, diagnosed with cancer, receiving chemotherapy, or receiving both agents were excluded from the study. Treatment episodes were constructed where a gap of greater than 60 days between the last day’s supply of ESA and next pharmacy dispensing was used to define a new treatment episode. Mean cumulative ESA dose was used to calculate drug cost (based on January 2009 wholesale cost) and dose ratio. Researchers identified 1311 patients (EPO 1,057; DARB 254). Patients taking EPO were slightly older (73.8 vs 72.8, P = 0.002). The proportion of women and comorbidities were similar between groups. Results showed that the mean [SD] cumulative dose during the most recent treatment episode was 220,883 [251,156] Units EPO and 799 [872] mcg DARB; dose ratio of 276:1 (Units EPO: mcg DARB). Corresponding drug cost was 27% higher with DARB than with EPO per episode ($3850 vs $3041, P = 0.005). After adjusting for covariates such as age, gender, payer, history, treatment characteristics, and initiation year, researchers found that cost savings associated with EPO remained significant.

This study was funded by Centocor Ortho Biotech Services, LLC.

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Bone Biology and Patient Care

Anaheim, CA—Osteoporosis is a common, chronic, progressive disease in postmenopausal women, and many elderly patients are at high risk of developing fractures because of it. Dr. Robert Feldman, a private practice physician and principal investigator and Medical Director for Senior Clinical Trials, Inc. in Laguna Hills, CA, discussed the importance of identifying and treating patients at risk for osteoporosis, at a lunch symposium at the ASCP meeting.

Women over age 50 have a 50% chance of a fracture in their lifetime without appropriate evaluation and treatment. Bone density testing together with risk factor assessment can identify persons at increased risk before they have a fracture of their hip or spine, and healthcare practitioners can intervene.

Bone mineral density (BMD) testing by DXA scan is recommended for: women age 65 and older and men age 70 and older; adults above age 50 with additional risk factors (adults who had fracture after age 50, adults with certain medical conditions such as rheumatoid arthritis or taking medications such as glucocorticoids, which are associated with bone loss); anyone being considered for treatment or being treated for osteoporosis.

The FRAX™ tool (available at www.NOF.org) can be used to integrate risk factors and BMD result to calculate absolute fracture risk over 10 years. Although it does have some limitations, it is another step forward in understanding an individual patient’s risk.

The 2008 National Osteoporosis Foundation guidelines recommend that clinicians consider FDA-approved medical therapies in postmenopausal women and men age 50 years and older, based on the following: a hip or vertebral (clinical or morphometric) fracture; T-score = -2.5 at the femoral neck, hip or spine after appropriate evaluation to exclude secondary causes; low bone mass (T-score between -1.0 and -2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture > 3% or a 10-year probability of a major osteoporosis-related fracture > 20% based on the U.S.-adapted WHO algorithm. Clinicians’ judgment and/or patient preference may indicate treatment for low bone mass patients with 10-year fracture probabilities above or below these levels.

Universal nonpharmacologic interventions include calcium and vitamin D supplementation, weight-bearing exercise, fall prevention, and avoiding tobacco and excessive alcohol use. The speaker emphasized the importance of clinicians measuring serum 25 OH vitamin D levels in patients.

Bone resorption by osteoclasts is coupled with bone formation by osteoblasts, which continuously remodel and adapt bones. Pharmacological interventions include antiresorptive agents, such as bisphosphonates, estrogen, estrogen agonists/antagonists, and calcitonin. An anabolic agent teriperatide is also available. Dr. Feldman also discussed the central role of RANK ligand (RANKL), which binds to the receptor RANK, a key mediator of osteoclast formation, function, and survival.

With any pharmacologic treatment, clinicians must look at factors that impact compliance, including side effects, dosing regimen, comorbid conditions, cognitive decline, patient motivation, and cost. A patient’s lack of persistence on oral bisphosphonates often negatively influences treatment outcomes. Regarding monitoring people on osteoporosis therapy, the speaker noted that Medicare covers bone turnover markers in addition to serial BMD to monitor patients on therapy. He also stressed the importance of encouraging ongoing dialogue with the patient when managing any chronic asymptomatic illness.

Dr. Feldman’s talk was sponsored by Amgen to provide knowledge and insight into the latest development into osteoporosis diagnosis and treatment. Not discussed at this meeting but of interest is denosumab, a novel investigational biologic drug given by subcutaneous injection, which is being developed by Amgen. Denosumab is a monoclonal antibody that targets the RANK ligand pathway. A recent study published in the New England Journal of Medicine (2009), compared this compound to placebo in 7868 ambulatory postmenopausal women age 60-90 years with osteoporosis. New vertebral fractures occurred in 2.3% of patients taking denosumab as compared to 7.2% of patients taking placebo, a 68% reduction (P < 0.001). New hip fractures were reduced by 40% with denosumab (1.2% vs 0.7%; P = 0.036). The adverse event profile was similar in both arms. This drug is currently seeking FDA approval.

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Treatment of Chronic Constipation in the Elderly

Anaheim, CA—Chronic constipation is frequently seen in LTC settings, with a prevalence of 63 million individuals, which is a higher rate of prevalence than coronary heart disease, asthma, and diabetes combined. Jonathan Shaatal, Director of Pharmacy at Four Seasons Nursing & Rehabilitation Center, Brooklyn, NY, spoke about the disorder at a dinner meeting held during the recent American Society of Consultant Pharmacists meeting, and emphasized the burden of chronic constipation, including impairment of productivity and negative effects on socialization in elderly adults. It affects more female than male individuals and is often caused by medications such as antacids, calcium, iron, nonsteroidal anti-inflammatory drugs, anticholinergic medications, and opioid analgesics.

The speaker discussed the importance of both nonpharmacologic and pharmacologic treatments for chronic constipation. Lifestyle changes include encouraging fluid intake, making sure that fruits, vegetables, and other fiber-rich foods are featured in the diet, getting regular exercise, and patients not ignoring the urge to evacuate. Stool softeners should be used for prevention, and treatment should start with bulk-forming laxatives. In addition, others that are often also used are bisocodyl, senna, or castor oil. There is some controversy as to how long stimulant laxatives should be used since they can damage the nerves of the colon causing “cathartic colon.” Saline laxatives can cause electrolyte imbalances, as can enemas, which can also be humiliating for patients to endure. Lactulose and sorbitol contain unabsorbable sugars and can cause flatulence. Polyethylene glycol can be taken for 7-14 days but can cause cramping and bloating. Probiotics contain healthy bacteria and may help normalize bowel function, but their effectiveness is uncertain. Prokinetic agents such as metoclopramide and erythromycin can cause diarrhea, and so should not be first choices.

A new class of medications, chloride-channel activators such as lubiprostone, can be useful for chronic constipation and constipation associated with irritable bowel syndrome. These appear to work locally, with low systemic availability and no drug interactions. The regimen for chronic constipation should be: Day 1: eliminate all laxatives; Day 2: start lubiprostone 24 mcg twice daily immediately after meals. Most patients have bowel movements within 3 days, averaging 4-5 bowel movements per week.

The speaker emphasized that this is an opportunity for one medication to replace multiple medications and enemas, reduce fecal impaction, decrease the time that nurses have to spend administering preparations, and reduce complaints from family members. He highlighted the case of a 69-year-old man with chronic constipation who was taking several laxatives. He was started on lubiprostone and now has on average four bowel movements per week.

While all Medicare Part D plans cover lubiprostone, some may impose step therapy or prior authorization. Consultant pharmacists can play an important role through use of the drug regimen review, focusing on the importance of reducing the number of medications a patient takes, improving quality of life, and examining standing versus as-needed orders. Many physicians will concur with their recommendations.