Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Long-Term Azithromycin for Prophylaxis of COPD Exacerbations

Source: Albert RK, et al. N Engl J Med 2011;365:689-698.

For many patients with moderate- severe chronic obstructive pulmonary disease, acute exacerbations (AECOPD) are highly problematic. For hospitalized AECOPD, the mortality rate is approximately 10%; loss of pulmonary function that typically accompanies an AECOPD is usually not regained; mortality during the year following an AECOPD is increased. Hence, reduction and/or delay of AECOPD is an important goal.

Macrolides are often the antimicrobial agents chosen to treat AECOPD. This trial in patients with COPD randomized subjects to azithromycin 250 mg qd (n = 570) or placebo (n = 572) for 1 year. The patient's background COPD treatments were unchanged. The primary outcome of the trial was time to first AECOPD. Secondary outcomes included QOL, and scores on the St. Georges Respiratory Questionnaire. More than three-fourths of study participants were receiving background inhaled steroids, long-acting beta agonists, and/or long-acting anticholinergics during the trial.

Azithromycin prophylaxis was associated with a statistically significant prolongation of time to first AECOPD, as well as a 27% relative-risk reduction in the frequency of AECOPD. The St. George's Respiratory Questionnaire scores were improved significantly more in the azithromycin group. One adverse effect analyzed was affect on hearing function: Azithromycin was associated with a slightly higher incidence of hearing decrement than placebo. However, improvements in hearing noted on follow-up occurred whether the drug was discontinued, suggesting that perhaps the incidence of hearing decrements were initially overestimated.

Azithromycin prophylaxis may provide important benefits in COPD, especially for persons with frequent AECOPD.

Unintended Medication Consequences of Hospital Admission

Source: Bell CM, et al. JAMA 2011; 306:840-847.

Most hospitalizations have a focused agenda: heart failure, pneumonia, acute trauma, etc. It is not at all difficult to conceive that as a consequence of intensified focus on one or more often acute problems, attention can be drawn away from the issues of lesser acuity, such as maintenance medications for dyslipidemia, dysglycemia, or thyroid disease. Sometimes because of discontinuity between persons involved in the patient's hospitalization and outpatient providers, inadvertent discontinuation of necessary chronic medications can be overlooked.

Using the database of patients in Ontario, Canada (n = 396,380; age 66 and older), Bell et al examined prescription data to see whether chronic medications from five different classes experienced discontinuation subsequent to hospitalization. The five classes were: statins, antiplatelet/anticoagulants, levothyroxine, respiratory inhalers, and gastric acid inhibitors.

Hospitalization was associated with an increased incidence of discontinuation of all five classes of agents. Hospitalization, which included ICU admission, was disproportionately likely to be associated with chronic medication discontinuation. Equally distressing, the data demonstrated an increased risk for death or subsequent hospitalization in persons who discontinued their chronic medications. Gaps in continuity of care are of significant consequence to hospitalized patients.

Is Mercury Really a Bad Guy in CV Disease?

Source: Houston MC. J Clin Hypertens 2011;13:621-627.

Mercury has a bad rap sheet: it decreases cellular oxidative defenses, increases oxidative stress, reduces the effectiveness of metalloenzymes, induces mitochondrial dysfunction, increases vascular inflammation, and worsens endothelial function. In addition, mercury toxicity is associated with increased carotid intima-media thickness. Omega-3 fatty acids, as contained in fish, can antagonize some of the detrimental effects of mercury. However, fish in the diet are also currently the major source of human exposure to mercury.

There is no known biologic or physiologic role of mercury in the body, hence it must be regarded as a toxin.

Observational data generally, but inconsistently, find an association between tissue levels of mercury and cardiovascular disease. For hypertension particularly, numerous different populations have found a relationship between tissue mercury levels and blood pressure (systolic, diastolic, and pulse pressure). Chronic mercury toxicity may be inexpensively measured by a 24-hour urine mercury level. The author does not include mention of any trials indicating favorable effects achieved by modulation of mercury, although selenium, by complexing with mercury, may mollify some of its toxic effects.