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Nesiritide, Scios' intravenous recombinant form of human B-type naturetic peptide, has been widely used for the treatment of congestive heart failure in hospitalized patients. On Scios' website, nesiritide is touted as the "best-selling IV cardiovascular drug ever brought to market.” All that may change with the publication of a new study that suggests that patients with acutely decompensated heart failure (ADHF) treated with nesiritide have a higher death rate at 30 days compared with patients who are not treated with the drug. The study was a pooled analysis of 12 randomized, controlled trials, of which 3 met all inclusion criteria. In those 3 trials, 485 patients with ADHF were randomized to nesiritide and 377 to control therapy which was noninotrope-based treatment. Thirty-day death rate was higher among the nesiritide group (7.2% vs 4.0% for placebo, 1.74 risk ratio; 95% CI [0.97-3.12]; P = .059). The authors conclude that therapy with nesiritide may be associated with increased risk of death after treatment for acutely decompensated heart failure, and suggest that an adequately powered, controlled trial should be undertaken (JAMA. 2005;293:1900-1905). This follows an earlier study that suggested nesiritide may worsen in renal function in patients with ADHF. In that study, which was also a pool analysis from 5 randomized studies, 1269 patients with ADHF were reviewed. Nesiritide was associated with a significantly increased risk of worsening renal function, compared with noninotrope control therapy (RR, 1.52; 95% CI, 1.16-2.0; P = .003) or any control therapy, including noninotrope and inotrope based therapies (RR, 1.54; 95% CI, 1.19-1.98 ; P = .001). Even low-dose nesiritide was found to worsen renal function. The authors conclude that nesiritide significantly increases the risk of worsening renal function in patients with ADHF, but suggests further investigation to determine the prognostic importance of this finding (Circulation. 2005;111:1487-1491).
Stopping Aspirin Before Surgery
A new study suggests that stopping aspirin 5 days prior to surgery is optimal. Researchers from Ireland recruited 51 volunteers who were randomly assigned to 3 groups: placebo, aspirin 75 mg per day, or aspirin 300 mg per day. Utilizing template bleeding times and specific platelet function testing, all bleeding times normalized within 96 hours and all platelet function test normalized within 144 hours after discontinuing aspirin. By day 6, there was no demonstrable hemostatic defect in any of the volunteers. There was also no difference between the 75 mg or 300 mg dose of aspirin. The authors conclude the data supports withholding aspirin for 5 days with elective surgery been performed on the sixth day (J Am Coll Surg. 2005;200:564-573). This study is important because of recent data that cardiovascular events are much more likely to occur in patients who had recently withdrawn from aspirin—with the peak of events occurring at 10 days (Pharmacology Watch. March, 2005). Safely stopping aspirin for 5 days prior surgery, with reinstitution as soon as possible after surgery, makes good clinical sense.
The Sponge Returns
The Today sponge contraceptive device is returning to the US market this summer. Last marketed more than 10 years ago, the sponge was removed from the market because of manufacturing problems. It is being brought back by Allendale pharmaceuticals, whose manufacturing facility met FDA standards. The sponge, which was made infamous by a memorable Seinfeld episode, is an over-the-counter, round, disposable, soft sponge that is impregnated with spermicide. It is inserted vaginally, and can be kept in place for 24 hours and for multiple sexual encounters. When it was taken off the market in 1994, the sponge was the most popular over-the-counter female contraceptive available, with 250 million of them sold in the 11 years it was available.
Preventing Metabolic Syndrome
Metformin and intensive lifestyle intervention both help prevent metabolic syndrome in patients who have impaired glucose intolerance. In a study derived from the Diabetes Prevention Program, 1711 patients with impaired glucose tolerance (defined by World Health Organization criteria plus fasting glucose level < 95) were evaluated. More than half the participants (53%) had metabolic syndrome at the baseline. In patients who did not have metabolic syndrome, metformin 850 mg twice daily or intensive lifestyle intervention designed to achieve and maintain 7% weight loss and 150 minutes of exercise per week were both effective in preventing metabolic syndrome. Lifestyle intervention was the more effective intervention with a 41% reduction in the incidence of metabolic syndrome (P < .001) while metformin reduced the incidence by 17% (P = .03) compared to placebo. Three-year cumulative incidences of metabolic syndrome were 51%, 45%, and 34% in the placebo, metformin, and lifestyle groups, respectively. The authors conclude that both lifestyle intervention and metformin are effective in reducing the development of metabolic syndrome in patients with glucose intolerance, although the impact of lifestyle intervention was more marked than that of metformin (Ann Intern Med. 2005;142:611-619).
FDA Actions
The FDA has approved exenatide for the treatment of type 2 diabetes in patients who have not responded to other treatments. The drug was derived from lizard saliva, and represents a new class of antidiabetic agents known as incretin mimetics—which mimic the effect of GLP-1, a naturally occurring incretin hormone found in human gut. Exanatide normalizes postprandial physiology by stimulating beta cells to secrete insulin in glucose dependent fashion. In alpha cells, the drug normalizes the pathologic hypersecretion of glucagon in a glucose dependent fashion. It also slows gastric emptying and improves satiety, all which serve to reduce postprandial hyperglycemia. There is some evidence that the drug may also attenuates weight gain seen with other hypoglycemic agents and may even be associated with weight loss. The drug will be marketed by Eli Lilly and Amylin Pharmaceuticals under the trade name Byetta.
Ropinirole (Requip) has been approved for the treatment of moderate-to-severe restless leg syndrome (RLS), the first US medication to be approved for this indication. The drug has been available for the treatment of Parkinson's disease since 1997. The approval was based on 3 randomized, double-blind, placebo-controlled trials in adults diagnosed with moderate to severe RLS. All 3 studies demonstrated a statistically significant improvement in the treatment group receiving ropinirole. Side effects include nausea, extreme drowsiness, and dizziness, and the drug will be labeled to warning about the possibility of falling asleep while engaged in activities of daily living including driving. GlaxoSmithKline is enthusiastic about the prospect of treating the estimated 1 out of 10 adults in this country with restless leg syndrome, the most common cause of insomnia.
This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: [email protected].
Nesiritide, Scios' intravenous recombinant form of human B-type naturetic peptide, has been widely used for the treatment of congestive heart failure in hospitalized patients.
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