Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
Febuxostat Compared with Allopurinol in Patients with Hyperuricemia and Gout
There have been no new agents approved to treat gout for over 20 years. Because the plasma becomes supersaturated at a uric acid level of 6.0 mg/dL, it is felt that persons with a diathesis for tissue deposition of urate (gouty arthritis, tophi, or both) will optimize benefit by maintaining serum uric acid (SUA) below this level. Although allopurinol (ALP) has been used with some success for many years, it is associated with intolerance in some patients, and commonly fails to achieve the goal of serum uric acid < 6.0 mg/dL. Finally, allopurinol is uncommonly associated with a hypersensitivity syndrome; this vasculitis has been fatal in as many as 25% of victims. Febuxostat (pronounced feb-u-zo-stat) is a new xanthine oxidase inhibitor which blocks uric acid production.
A trial of patients with gout (n = 762) randomly assigned subjects to febuxostat 80 mg or 120 mg qd vs allopurinol. Allopurinol was dosed at 300 mg/d except in those requiring dosage adjustment due to renal insufficiency. The primary end point of this 1 year study was ability to achieve a SUA < 6 mg/dL, confirmed for each of the last three study months.
Febuxostat 80 mg and 120 mg were more effective than ALP for percent of individuals able to achieve and maintain SUA < 6 (53%, 62%, and 21% respectively). During the trial, frequency of gout flares was similar in all groups.
Becker MA, et al. N Engl J Med. 2005;353:2450-2461.
Prognostic Value of Serial B-Type Natriuretic Peptide Testing During Follow-up of Patients with Unstable Coronary Artery Disease
Brain-type natriuretic peptide (BNP) has been found to be useful to differentiate etiologies of dyspnea in patients presenting to emergency departments, as a diagnostic tool for heart failure, and as a metric for following adequacy of treatment in heart failure. BNP is released in relation to ventricular wall stress, and elevations of BNP are also seen after acute coronary syndromes (ACS). Elevations of BNP in ACS have been found to be strongly associated with overall mortality, and specifically with onset of new congestive heart failure. Conclusions about the utility of BNP in ACS are primarily based upon a limited number of BNP measurements temporally associated with the acute cardiac event. Whether more persistent monitoring of BNP levels might prove useful as a predictive marker for increased risk was the subject of this study.
Morrow et al monitored BNP levels in ACS patients (n = 4,266) at hospitalization, 4 months, and 12 months. The primary end point was death or new CHF. Subjects with a BNP > 80 pg/mL at each measurement cycle had a dramatically worse prognosis for the primary outcome. At 4 months, an increase BNP was associated with a 2.5 hazard ratio for death/CHF, and at 12 months a 4.7 hazard ratio. Just looking at the end point of mortality, an elevated BNP was associated with a doubled long-term risk.
Morrow DA, et al JAMA. 2005;294: 2866-2871.
Dietary Fiber Intake and Risk of Colorectal Cancer
There have been a number of mechanisms suggested to support the concept that increased dietary fiber might reduce risk for colon cancer (COL): dilution of fecal carcinogens, reduced fecal transit time, enhanced production of anticarcinogenic short chain fatty acids, and binding of carcinogenic bile acids. While each of these effects may occur from fiber enhancement, observational studies which evaluate the relationship between dietary fiber and COL have provided conflicting results.
Park et al performed a pooled analysis of 13 prospective cohort studies that examined dietary fiber and colon cancer. Study subjects (n = 725,628) were adults who had been followed for 6-20 years.
Although univariate analysis was optimistic in suggesting a 16% relative risk reduction for COL in the highest quintile of fiber intake versus the lowest, subsequent multivariate analysis was unable to confirm this benefit. Despite the intellectual appeal of fiber intake as a preventative for COL, the data do not support an independent benefit.
Park Y, et al. JAMA. 2005;294: 2849-2857.
Febuxostat Compared with Allopurinol in Patients with Hyperuricemia and Gout; Prognostic Value of Serial B-Type Natriuretic Peptide Testing During Follow-up of Patients with Unstable Coronary Artery Disease; Dietary Fiber Intake and Risk of Colorectal CancerYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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