Abstracts from Medical Literature for the the Geriatrics Practitioner

ADVERSE EFFECTS OF BETA-BLOCKER THERAPY FOR PATIENTS WITH HEART FAILURE

Studies have shown that the use of beta-blocker therapy in patients with heart failure (HF) with systolic dysfunction reduces mortality and hospitalizations in this population, a therapy previously thought to be contraindicated in these patients. Systematic reviews of beta-blocker trials in patients with HF have demonstrated reductions in mortality of approximately 30%, and clinical practice guidelines strongly recommend the use of beta-blockers. The same clinical guidelines, however, highlight common cardiovascular adverse effects associated with beta-blocker therapy, including HF deterioration, hypotension, dizziness, bradycardia, and fatigue. Concerns about adverse effects may deter clinicians from prescribing this life-saving therapy. Although individual HF trials have reported the risks of these adverse effects, no study has combined the available information to obtain the best estimates of these risks during beta-blocker therapy. In this study, the authors performed an overview of randomized beta-blocker trials in patients with HF to quantify the risks of cardiovascular adverse effects.

Heart failure trials of beta-blockers were identified by electronic searches of the MEDLINE database from 1966-2002. The random-effects model was used to combine results from individual trials and calculate estimates of risks associated with therapy. Beta-blocker therapy was associated with significant absolute increases in risks of hypotension (11 per 1000; 95% confidence interval [CI], 0-22), dizziness (57 per 1000; 95% CI, 11-104), and bradycardia (38 per 1000; 95% CI, 21-54). There was no significant absolute risk of fatigue associated with therapy (3 per 1000; 95% CI, -2 to 9). Beta-blocker therapy was associated with a reduction in all-cause withdrawal of medication (14 per 1000; 95% CI, -2 to 29), as well as significant reductions in all-cause mortality (34 per 1000; 95% CI, 20-49), HF hospitalizations (40 per 1000; 95% CI, 22-58), and worsening HF (52 per 1000; 95% CI, 10-94). The authors concluded that although beta-blocker therapy was associated with hypotension, dizziness, and bradycardia, the absolute increases in risk were small, and overall fewer patients were withdrawn from beta-blocker therapy than from placebo. This information should alleviate concern about prescribing this life-saving therapy to patients with HF.

Ko DT, Hebert PR, Coffey CS, et al. Adverse effects of beta-blocker therapy for patients with heart failure: A quantitative review of randomized trials. Arch Intern Med 2004;164:1389-1394.

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USE OF BETA-BLOCKERS AND RISK OF FRACTURES

Animal studies suggest that the beta-blocker propranolol increases bone formation, but data is limited on whether use of beta-blockers—with or without concomitant use of thiazide diuretics—is associated with reduced fracture risk in humans. The objective of this study was to determine whether the use of beta-blockers alone or in combination with thiazides is associated with a decreased risk of fracture in adults. Data were derived from the UK-based General Practice Research Database (GPRD); more than 3 million persons are enrolled with selected general practitioners who use office computers and have agreed to provide data for research purposes. The study included 30,601 case patients age 30-79 years with an incident fracture diagnosis between 1993-1999, and 120,819 controls, matched to cases on age, sex, calendar time, and general practice attended. Authors found that the most frequent fractures were of the hand/lower arm (n = 12,837 [42.0%]) and of the foot (n = 4627 [15.1%]). Compared with patients who did not use either beta-blockers or thiazide diuretics, the odds ratio (OR) for current use of beta-blockers only (≥ 3 prescriptions) was 0.77 (95% confidence interval [CI], 0.72-0.83); for current use of thiazides only (≥ 3 prescriptions), 0.80 (95% CI, 0.74-0.86); and for combined current use of beta-blockers and thiazides, 0.71 (95% CI, 0.64-0.79). Data were adjusted for smoking, body mass index, number of practice visits, and use of calcium-channel blockers, angiotension-converting enzyme inhibitors, antipsychotics, antidepressants, statins, antiepileptics, benzodiazepines, corticosteroids, and estrogens. The authors concluded that the data suggest that current use of beta-blockers is associated with a reduced risk of fractures, taken alone as well as in combination with thiazide diuretics. Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with beta-blockers and thiazides.

Schlienger RG, Kraenzlin ME, Jick SS, Meier CR. Use of beta-blockers and risk of fractures. JAMA 2004; 292:1326-1332.

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BENZODIAZEPINE USE AND HIP FRACTURES IN THE ELDERLY

Data about the relationship between benzodiazepine use and the incidence of hip fracture remain conflicting. Two landmark case-control studies published about 15 years ago suggested that use of long elimination half-life hypnotic-anxiolytic agents in general, and use of long elimination half-life benzodiazepines in particular, increase elderly patients’ risk for hip fracture. Since then, some studies have confirmed associations between benzodiazepine use and falls, and between long half-life benzodiazepine use and risk of fall and hip fracture. Others found increased risk of hip fracture only with short elimination half-life benzodiazepines, while some studies failed to detect a relationship between benzodiazepine use and incidence of falls or hip fracture. Studies that investigated the effects of duration of use on risks of fall, fall-related hospitalization, and hip fracture found increased risks during the first 2 weeks of benzodiazepine treatment, but differ in conclusions regarding the risk of benzodiazepine use after that time. Confounding by indication and benzodiazepine exposure misclassification may account for some of the differences in results.

The authors of this study examined the relationship in a large cohort, controlling for multiple potential confounders. They analyzed 42 months of New Jersey Medicaid health care claims data for all enrollees. Each eligible person-day was assigned to categories of benzodiazepine exposure and categories of other predictors, based on prior and current medication dispensing and diagnosis information. Hip fractures were identified based on hospital claims with primary discharge diagnosis International Classification of Diseases, Ninth Revision (ICD-9) codes 820.xx. Cohort members (n = 125,203) contributed 194,071 person-years and had 2312 eligible hip fractures. After adjustment for age, sex, race, Medicaid nursing home residence, exposure to other psychoactive medications (including antiparkinsonian medications), diagnoses of epilepsy and dementia, and hospitalization in the previous 6 months, the incidence of hip fracture was significantly higher compared with no benzodiazepine use for exposure to any benzodiazepine (incidence rate ratio [IRR], 1.24; 95% confidence interval [CI], 1.06-1.44), to a short half-life, high-potency benzodiazepine (IRR, 1.27; 95% CI, 1.01-1.59), during the first 2 weeks after starting a benzodiazepine (IRR, 2.05; 95% CI, 1.28-3.28), during the second 2 weeks after starting a benzodiazepine (IRR, 1.88; 95% CI, 1.15-3.07), and for continued use (IRR, 1.18; 95% CI, 1.03-1.35). The authors concluded that the incidence of hip fractures appeared to be associated with benzodiazepine use. Contrary to several previous studies, short half-life benzodiazepines are not safer than long half-life benzodiazepines. Hip fracture risk is highest during the first 2 weeks after starting a benzodiazepine, and declines thereafter.

Wagner AK, Zhang F, Soumerai SB, et al. Benzodiazepine use and hip fractures in the elderly. Arch Intern Med 2004;164:1567-1572.