Medication use is an important consideration in studying the relationship between disease and disability. Drug therapy can substantially modify the risk and progression of conditions that cause disability. For example, the incidence of two major causes of disability-stroke and hip fracture-can be reduced by appropriate pharmacological treatment of systolic hypertension and osteoporosis, respectively (LaCroix et al., 1990; SHEP Cooperative Research Group, 1991; Storm et al., 1990). Also, treatment of congestive heart failure with angiotensin converting enzyme (ACE) inhibitors can decrease morbidity and improve survival, compared with conventional therapies (Pfeffer et al., 1992; SOLVD Investigators, 1992). Conversely, certain drugs can cause adverse reactions that, at least in some patients, may offset the beneficial effects and possibly aggravate prevalent diseases (Carbonin et al., 1991). For instance, digoxin toxicity is not uncommon and increases among the oldest old (Pahor et al., 1993), and continued use of cathartics may be associated with an increased risk of hypoalbuminemia (Pahor et al., 1994b), an important predictor of total and cardiovascular mortality (Corti et al., 1994).
Determining prescribed medications is also useful in epidemiologic research as an adjunct to self-report for determining disease presence and severity. Conditions such as angina, congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, cancer, and Parkinson's disease are treated with specific prescription drugs.
This chapter describes the medications taken most frequently by participants in the Women's Health and Aging Study (WHAS) and provides several examples of how specific drugs may be related to health and functioning in older women. This information may be useful for planning further research on medication use in the older population.
Each participant was asked if she had taken any prescription or nonprescription medication in the past 2 weeks. If she answered yes, she was asked to present all medicine containers. The interviewer recorded the medication name, whether it was prescribed or over-the-counter (OTC), and the form, strength, and prescribed dosage. The interviewer also asked how much the participant actually took. If the medication container was not available, only the name, whether prescription or OTC, and the amount taken were ascertained. This method of medication ascertainment is similar to that used in other epidemiological studies (Pahor et al., 1994a) and has been demonstrated to be valid and reliable (Landry et al., 1988; Psaty et al., 1992). To facilitate data entry, all medications were coded according to a 7-digit numerical code that identifies specific drug products, strengths, and forms. For analytical purposes, these drug product codes were converted into an 8-digit numerical coding system that identifies specific ingredients and four hierarchical levels of therapeutic and chemical categories (Pahor et al., 1994a).
Eighty-eight percent of these disabled women reported taking prescription medications during the 2 weeks before the baseline interview (Table 15.1). Medication use was slightly lower among the oldest old and slightly higher among women receiving help with activities of daily living (ADLs). Seventy-eight percent of the women reported taking nonprescription drugs. The rates of prescription medication use are slightly higher than those reported in the Established Populations for Epidemiologic Studies of the Elderly (EPESE; Chrischilles et al., 1992), which ranged from 68 to 78 percent of women. Chrischilles and colleagues reported that rates of prescription drug use were significantly higher among women limited in walking, climbing stairs, and performing heavy housework, ranging from about 80 to 90 percent. Rates of OTC drug use were similar in the WHAS and the EPESE. Nationally, in 1987, 84.5 percent of women age 65 years and older used prescription medications (Moeller and Mathiowetz, 1989).
Table 15.2 presents rates of medication use in the principal drug categories and according to ingredients, expressed as the percentage of participants taking these drugs. As expected, the most frequently taken medications are in the following categories: cardiovascular drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), diuretics, and vitamins. The use of medications such as corticosteroids and anticoagulants, which may indicate the presence of a severe underlying disease, was about twice as frequent in WHAS participants as among a general older population (Pahor et al., 1994c). These participant-based rates of use are lower than drug-based rates would be for two reasons. First, a participant may have taken more than one medication within a specific category. For example, a
participant may have taken digoxin, nitroglycerin, and enalapril, which are all in the cardiovascular drug category. In fact, participants taking cardiovascular drugs averaged 1.8 medications per person in this category. Second, some medications contain two or more ingredients in combination (e.g., certain brands of antacids that contain both aluminum hydroxide and magnesium hydroxide, and cathartic medications that are a combination of ingredients).
Acetaminophen and aspirin were the most frequently taken drug ingredients (38.0 and 36.9 percent, respectively), and ibuprofen was the most frequently used NSAID after aspirin (11.6 percent). A positive aspect of this finding is that, among NSAIDs, ibuprofen has the lowest risk of severe adverse reactions such as gastrointestinal hemorrhage (Kaufman et al., 1993; Pahor et al., 1994c). Overall, 55 percent of participants used one or more NSAIDs. Opioid analgesics were also used relatively frequently (5.9 percent). Although aspirin may have been prescribed as a platelet antiaggregant for some participants, these findings show that pain relief was a major concern in the WHAS population.
Among cardiovascular drugs used for treating hypertension, calcium antagonists were the most frequently taken, followed by ACE inhibitors and beta-blockers. This pattern differs from that of a 1988 study, which found that beta-blockers were more commonly used for hypertension in older patients than calcium antagonists and ACE inhibitors (Pahor et al., 1995). Changes in drug use over time have been documented by longitudinal studies (Glynn et al., 1995; Manolio et al., 1995; Psaty et al., 1995), and this fact could have an impact on morbidity and mortality in the WHAS. The frequent use of nitrates (20.1 percent), indicates that about one out of five participants had treated angina.
Thyroid hormones were used relatively frequently (9 percent); it is unclear whether this high rate reflects clinical hypothyroidism or use of these drugs for other conditions. The use of thyroid hormones has been associated with an increased risk for osteoporosis (Schneider et al., 1994) and therefore might increase the incidence of hip fracture and aggravate disability.
A great deal of additional information is available in Table 15.2. Highlights of interest include:
· The rate of use of tamoxifen, a drug prescribed for breast cancer, was 1.6 percent.
· The rate of antiarrhythmic drug use was 1.9 percent.
· The rate of digoxin use was 13.5 percent.
· The rate of antilipemic (cholesterol-lowering) medication use was 8.6 percent.
· The rate of benzodiazepine use was 8.8 percent.
· The rates of calcium supplement and vitamin D use were relatively low (4.1 and 3.1 percent, respectively).
· The rate of diuretic use was quite high (38.9 percent).
· The rates of use of oral hypoglycemic drugs and insulin were 8.7 and 4.8 percent, respectively.
· The rate of estrogen use was 7.7 percent.
Medication use among participants in the WHAS was high, with sufficient numbers to estimate rates for selected ingredients, the most common of which are shown in Table 15.2. The WHAS has the unique advantage of studying disabled older persons, who are usually excluded from large clinical trials because of their difficulty in making repeated visits to a clinic and complying with a demanding protocol. Evaluation of adverse and beneficial effects may help to clarify the potential impact of medication use on disability.
Carbonin PU, Pahor M, Bernabei R, Sgadari A. (1991). Is age an independent risk factor of adverse drug reactions in hospitalized medical patients? J Am Geriatr Soc 39:1093-1099.
Chrischilles EA, Foley DJ, Wallace RB, Lemke JH, Semla TP, Hanlon JT, Glynn RJ, et al. (1992). Use of medications by persons 65 and over: Data from the Established Populations for Epidemiologic Studies of the Elderly. J Gerontol Med Sci 47:M137-M144.
Corti MC, Guralnik JM, Salive ME, Sorkin JD. (1994). Serum albumin level and physical disability as predictors of mortality in older persons. JAMA 272:1036-1042.
Glynn RJ, Brock DB, Harris T, Havlik RJ, Chrischilles EA, Ostfeld AM, Taylor JO, et al. (1995). Use of antihypertensive drugs and trends in blood pressure in the elderly. Arch Intern Med, in press.
Kaufman DW, Kelly JP, Sheehan JE, Laszlo A, Wiholm BE, Alfredsson L, Koff RS, et al. (1993). Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. Clin Pharmacol Ther 53:485-494.
LaCroix AZ, Wienpahl J, White LR, Wallace RB, Scherr PA, George LK, Cornoni-Huntley J, et al. (1990). Thiazide diuretic agents and the incidence of hip fracture. N Engl J Med 322:286- 290.
Landry JA, Smyer MA, Tubman JG, Lago DJ, Roberts J, Simonson W. (1988). Validation of two methods of data collection of self- reported medicine use among the elderly. Gerontologist 28:672-676.
Manolio TA, Cutler JA, Furberg CD, Psaty BM, Whelton PK, Applegate WB. (1995). Trends in pharmacologic management of hypertension in the United States. Arch Intern Med 155:829-837.
Moeller J, Mathiowetz N. (1989). Prescribed medicines: A summary of use and expenditures by Medicare beneficiaries. National Medical Expenditure Survey Research Findings No. 3, National Center for Health Services Research and Health Care Technology Assessment. DHHS Pub. No. (PHS) 89-3448. Rockville, MD: Public Health Service.
Pahor M, Guralnik JM, Gambassi G, Bernabei R, Carosella L, Carbonin PU. (1993). The impact of age on the risk of adverse drug reactions to digoxin. J Clin Epidemiol 46:1305-1314.
Pahor M, Chrischilles EA, Guralnik JM, Brown SL, Wallace RB, Carbonin PU. (1994a). Drug data coding and analysis in epidemiologic studies. Eur J Epidemiol 10:405-411.
Pahor M, Guralnik JM, Chrischilles EA, Wallace RB. (1994b). Use of laxative medication in older persons and associations with low serum albumin. J Am Geriatr Soc 42:50-56.
Pahor M, Guralnik JM, Salive ME, Chrischilles EA, Wallace RB. (1994c). Disability and severe gastrointestinal hemorrhage: A prospective study of community dwelling older persons. J Am Geriatr Soc 42:816-825.
Pahor M, Guralnik JM, Corti C, Foley DJ, Carbonin PU, Havlik RJ. (1995). Long term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc, in press.
Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ, Cuddy TE, Davis BR, et al. (1992). Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 327:669-677.
Psaty BM, Koepsell TD, Yanez ND, Smith NL, Manolio TA, Heckbert SR, Borhani NO, et al. (1995). Temporal patterns of antihypertensive medication use among older adults, 1989 through 1992: An effect of the major clinical trials on clinical practice? JAMA 273:1436-1438.
Psaty BM, Lee M, Savage PJ, Rutan GH, German PS, Lyles M for the CHS Collaborative Research Group. (1992). Assessing the use of medications in the elderly: Methods and initial experience in the Cardiovascular Health Study. J Clin Epidemiol 45:683- 692.
Schneider DL, Barrett-Connor EL, Morton DJ. (1994). Thyroid hormone use and bone mineral density in elderly women: Effects of estrogen. JAMA 271:1245-1249.
SHEP Cooperative Research Group. (1991). Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 265:3255-3264.
SOLVD Investigators. (1992). Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327:685-691.
Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH. (1990). Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 322:1265-1271.