Pharmacology Watch
Beta-Blockers May Be Useful for Noncardiac Surgery
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High risk patients benefit from perioperative beta-blockers when undergoing major noncardiac surgery according to new study. Researchers from Tufts University reviewed the records of 782,969 patients in 2000 and 2001 at 329 hospitals throughout the United States. Patients were graded with the Revised Cardiac Risk Index (RCRI), which takes into account high-risk surgery, ischemic heart disease, cerebrovascular disease, renal insufficiency, and diabetes. The RCRI is graded on a 0-5 point scale, with 5 representing the highest risk. High risk surgery included all intrathoracic, intraperitoneal, and superinguinal vascular procedures. Patients with contraindications to beta blocker therapy were excluded. Over 660,000 patients had no contraindications to beta-blockers, and 120,338 patients received beta-blocker treatment during the first 2 hospital days. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk. Patients with an RCRI of 0 or 1 were found to have no benefit from beta-blocker treatment, whereas for patients with an RCRI of 2, 3, or 4, or more the adjusted odds ratio for death in the hospital, were 0.88 (95% CI, 0.80, 0.80-0.98), 0.71 (95% CI, 0.63 - 0.80) and 0.58 (95% CI, 0.50-0.67), respectively. The authors conclude that perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk patients undergoing major noncardiac surgery. They also noted that there was no benefit for low risk patients (Lindenauer PK, et al. Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery. N Engl J Med. 2005;353:349-361). An accompanying editorial points out that perioperative beta-blocker therapy has been somewhat controversial because of conflicting data in recent years. The current study shows an apparent benefit in high-risk patients, but they also look forward to the results of 2 ongoing randomized trials that will help clarify the role of beta-blockers for low-risk and intermediate-risk patients (Poldermans D, et al. Beta-Blocker Therapy in Noncardiac Surgery. N Engl J Med. 2005;353:412-414).
Promising New Weight Loss Drug?
More data shows that topiramate (Topamax) is associated with weight loss and, in this latest study, may also lower blood pressure in obese, hypertensive patients. In a study from Norway, 531 obese patients with hypertension were randomized to placebo, topiramate 96 mg/day, or topiramate 192 mg/day. All patients received the same diet, exercise, and behavioral modification advice. Patients were followed for 28 weeks. Mean weight loss was 1.9% for placebo and 5.9% and 6.5% for the 96 mg and 192 mg doses, respectively (P < 0.001 for each compared with placebo). Diastolic blood pressure was reduced 2.1, 5.5, and 6.3 mm Hg, respectively (P < 0.015 vs placebo). Systolic blood pressure was reduced 4.9, 8.6, and 9.7 mm Hg, respectively (P = NS). Paresthesia occurred in 33% of the active treatment group. The authors conclude that topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects (Tonstad S, et al. Efficacy and Safety of Topiramate in the Treatment of Obese Subjects with Essential Hypertension. Am J Cardiol. 2005;96:243-251).
Treating Shift-Work Disorder
Modafinil (Provigil) may be of some value for people with excessive sleepiness associated with shift-work sleep disorder. Researchers from Harvard randomized 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Modafinil resulted in modest improvement in nighttime sleep latency (1.7 + 0.4 vs 0.3 + 0.3 minutes, respectively; P = 0.002). More patients also had improvement in their clinical symptoms based on multiple objective tests and patients diaries (74% vs 36%, respectively; P < 0.001). Patients taking modafinil also had reduction in frequency and duration of lapses in attention during nighttime testing of performance, and proportionally fewer patients reported having had accidents or near accidents while commuting home (both P < 0.001). These benefits, however, were mild, and patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. The authors conclude that modafinil 200 mg at the beginning of a shift may improve shift-worker's performance as compared to placebo, although the benefit is modest (Czeisler CA, et al. Modafinil for Excessive Sleepiness Associated with Shift-Work Disorder. N Engl J Med. 2005;353:476-486). An accompanying editorial urges caution when interpreting these results and suggests "the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil." The authors do note that up to 20% of workers in industrialized nations are shift-workers and calls for "further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of us having become, to a large extent, a shift-working society" (Basner RC. Shift-Work Sleep Disorder--The Glass is More Than Half Empty. N Engl J Med. 2005;353:519-521).
Another Flu Vaccine Shortage?
With the flu season looming, Chiron Corp. is again having difficulty with flu vaccine production. Last year the company found contamination at its Liverpool production plant, a situation that cause severe shortages of vaccine in the United States. This year, the company has discovered contamination at a German plant and is stating that it can only provide vaccine for the US market. The German plant was primarily the source of the Begrivac flu vaccine, which was sold on the world market. The company is making "substantial progress" in fixing problems at the Liverpool plant where the US vaccine is made. Meanwhile, Acambis plc is working on a universal flu vaccine that could offer permanent protection against all types of influenza. The company hopes to generate a universal vaccine that would not require annual changes in formulation and would protect against both influenza A and B including avian strains. The company, however, states that it may require years of clinical trials before earning approval. Fears of avian influenza pandemic have prompted the French company Sanofi-Aventis to work on a vaccine for the avian H5N1 strain that has killed millions of birds and 50 people in Asia. Preliminary results are promising, however, full-scale production could take months, according to Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases.
FDA Actions
The FDA has approved the first of the new class of drugs for the treatment of insomnia characterized by difficulty with sleep onset. Takeda Pharmaceutical's ramelteon (Rozerem) is a selective agonist at 2 melatonin receptors in suprachiasmatic nucleus, receptors that are thought to regulate circadian rhythm and sleepiness. Recently marketed sleeping medications target GABA receptors (ambien, lunesta) and, although these drugs are associated with less addiction and sleep latency then benzodiazepines, they are still designated as Schedule IV drugs. Ramelteon has shown no evidence of abuse or dependence potential and will, therefore, be marketed as a unscheduled drug. It is also approved for long-term use and has not been associated with memory impairment or impairment of motor ability. The most common adverse events associated with ramelteon were somnolence, fatigue and dizziness (> 2% over placebo).
Plan B, Barr Pharmaceutical's "morning-after pill" is being considered for over-the-counter approval by the FDA. The issue has become a political hot potato, and even briefly held up the Senate's confirmation of Lester Crawford, MD, as Commissioner of the FDA. It is expected that decision will be made by September.
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].
Beta-Blockers May Be Useful for Noncardiac Surgery; Promising New Weight Loss Drug?; Treating Shift-Work Disorder; Another Flu Vaccine Shortage?; FDA ActionsSubscribe Now for Access
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