Clinical Briefs
Clinical Briefs
By Louis Kuritzky, MD
Inhaled Zanamivir for the Prevention of Influenza in Families
Influenza (flu) remains a major source of morbidity and mortality in the United States, despite the widespread availability of vaccine and antiviral pharmacotherapies. Prevention of influenza by antiviral drug therapy has, until quite recently, been limited by the fact that amantadine and rimantadine are only efficacious against influenza A. Two new neuraminidase inhibitors—zanamivir and oseltamivir—are not only effective against both influenza A and influenza B, but in contrast to prior antiviral drug use, they have not been thus far associated with emergence of drug-resistant influenza strains.
At the time of this writing, only oseltamivir (Tamiflu) is approved for prophylaxis of influenza. This study used zanamivir (Relenza) in an attempt to reduce family member influenza in a large group of subjects (n = 321) who developed an influenza-like illness (ILI) during the 1998-1999 flu season.
Once an index case came down with an ILI, either zanamivir 10 mg qd (by inhalation) or placebo was given to household contacts for 10 days. The index case was treated with the therapeutic FLU dose, 10 mg b.i.d. for five days.
There was a striking difference in the frequency with which previously healthy household contacts came down with ILI if they received zanamivir: 4% vs. 19% on placebo. No serious adverse events occurred.
Zanamivir, in a standard dose administered by inhalation once daily, appears to be an effective and safe intervention for prevention of influenza A and B; its efficacy for treatment of FLU has been previously established. v
Hayden FG, et al. N Engl J Med 2000;343:1282-1289.
Aspirin and ACEIs in Patients with CAD
When used individually, both aspirin (ASA) and angiotensin-converting enzyme inhibitors (ACEIs) have shown a favorable secondary prevention effect among patients with ischemic heart disease. Intuitively, one would expect that the combination of these agents might produce even greater advantage. On the other hand, ASA has been shown to antagonize the hemodynamic effects of ACEI in hypertension, and retrospective studies have intimated that ASA might reduce ACEI benefits in persons with heart failure. The current report analyzed the effect of ASA when combined with ACEI (ASA/ACEI) on mortality in a large trial of patients with coronary artery disease who had been treated as part of the GUSTO-I trial (n = 41,021) and the EPILOG trial (n = 2619). The analysis was retrospective; no prospective trials to assess the effect of ASA/ACEI on morbid or mortal end points have been performed.
In the GUSTO trial, ASA/ACEI use was associated with a statistically significantly greater unadjusted mortality rate than ASA alone; however, ACEI-treated patients had more hypertension and anterior MI at baseline. In the EPILOG trial, the ASA/ACEI group also showed a greater unadjusted mortality rate than ASA alone. Even after multivariate analysis adjusted for potential confounders, ASA/ACEI treatment appeared to be associated with an increased hazard risk of death. One of the mechanisms by which ASA is described to compete with beneficial effects of ACEI is that bradykinin, which is enhanced by ACEI, stimulates vasodilatory prostaglandins. ASA inhibits such prostaglandins.
Because the study is observational, causality between ASA/ACEI and adverse outcome has not been conclusively established. However, such observational information should prompt the formulation of a prospective randomized trial to resolve the issue. v
Peterson JG, et al. Am J Med 2000; 109:371-377.
Treating Intermittent Claudication
Medical therapies for intermittent claudication (IC) are few. Pentoxifylline (PTF) was the only approved agent from 1984-1999. Recently, cilostazol (CSL) has been added to the therapeutic choices. It has been shown to be effective for improvement in walking distance on a treadmill; additionally, IC patients report improved physical function when treated with CSL.
Patient selection for this double blind placebo-controlled trial of PTF vs. CSL (n = 539) included the presence of stable IC for at least six months, documentation of peripheral arterial disease (post-exercise ankle pressure reduced at least 20 mm Hg, or at least 10 mm Hg with an abnormal ankle/brachial index), and ability to adequately complete treadmill testing. Patients were evaluated at baseline and monthly for six months of treatment (CSL 100 mg B.I.D., PTF 400 mg T.I.D., or placebo). All patients received three doses daily (i.e., CSL treatment included 1 "dummy" capsule) to maintain the double-blind status of the trial.
By week four of evaluation, and continuing through the conclusion of the trial, CSL-treated patients enjoyed a statistically significant increase in maximal treadmill walking distance when compared to placebo or PTF. Improvements in patients treated with PTF were not superior to placebo. Overall, all treatments were well tolerated, though headache and diarrhea were more frequent in CSL-recipients.
Previous reports have brought the clinical efficacy of PTF into question. The efficacy of CSL appears to be well substantiated.
Dawson DL, et al. Am J Med 2000;109:523-530.
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