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By William T. Elliott, MD, FACP
In patients with vascular disease and arthritis, taking ibuprofen may block the beneficial anti-platelet aggregation effects of low-dose aspirin. Researchers from the University of Pennsylvania found that taking ibuprofen 400 mg 2 hours before taking aspirin significantly reduced aspirin’s benefits. Conversely, taking aspirin 2 hours before ibuprofen had no effect on aspirin’s anti-platelet action. It is speculated that ibuprofen occupies the hydrophobic channel of platelet Cox-1, effectively blocking aspirin’s access to platelet cyclooxygenase. In the same study, pretreatment with acetaminophen or the selective Cox-II inhibitor rofecoxib had no effect on aspirin’s action. The study also showed that therapeutic levels of the anti-inflammatory diclofenac did not affect aspirin’s anti-platelet action, whereas regular doses of ibuprofen (400 mg 3 times a day) did block aspirin’s beneficial action. This study concludes that ibuprofen, and perhaps some other nonselective NSAIDs, may block the beneficial platelet inhibition of aspirin (N Engl J Med. 2001;345:1809-1817; 1844-1876).
Intravenous droperidol (Inapsine-Akorn pharmaceuticals) has received a "Black Box" warning from the FDA because of the risk of fatal heart arrythmias associated with the drug. The Black Box, the highest-level warning assigned to drugs, was accompanied by a "Dear Doctor" letter to US physicians. Droperidol is commonly used in the in-patient setting to treat nausea and anxiety. Low doses of the drug have been shown to result in prolongation of the QT interval, while higher doses (more than 25 mg) have been associated with fatal ventricular arrhythmias including torsade de pointes. The FDA is urging physicians to consider use of alternative medications for patients at high risk for cardiac arrhythmias.
The angiotensin-receptor blocker valsartan improves clinical signs and symptoms of congestive heart failure and may reduce the incidence of hospitalization in patients with advanced heart failure. More than 5000 patients with NYHA class II, III, or IV heart failure were randomly assigned to receive 160 mg valsartan or placebo. Patients had been on a fixed-dose regimen of ACE inhibitors, diuretics, digoxin, and/or beta-blockers. The primary outcomes were mortality and the combined end point of mortality and morbidity including cardiac arrest with resuscitation, hospitalization for heart failure, or receipt of intravenous heart failure of medications. The overall mortality of the 2 groups was not different, however the incidence of the combined end point was 13.2% lower in the valsartan group. This was primarily due to a decrease in the number of patients requiring hospitalization. Valsartan also improved ejection fraction, signs and symptoms of heart failure, and quality of life compared to placebo. Interestingly, when valsartan was combined with an ACE inhibitor and a beta blocker, there was an increase in mortality and morbidity (N Engl J Med. 2001;345:1667-1675).
The 3 most commonly used antidepressants are all comparable in reducing depressive symptoms according to a recent large-scale trial. Paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) were found to be equivalent in treating depression in the primary care setting. More than 570 patients with depression were randomized to receive paroxetine 20 mg/d, fluoxetine 20 mg/d, or sertraline 50 mg/d. Follow-up interviews were done at 1 month, 3 months, 6 months, and 9 months. All 3 drugs were equally effective and comparable on all measures at all time points. About 20% of patients switched drugs during the course of the study, although the rate of side effects was similar among all 3 drugs. The study concludes that the 3 drugs are similar in effectiveness for treatment of depressive symptoms up to 9 months of treatment (JAMA. 2001;286:2947-2955). The findings of the study are particularly interesting given that fluoxetine has recently lost its patent protection, and low-cost generics are available.
Zinc nasal spray is ineffective for preventing or treating the common cold according to a new study. Investigators from the University of Virginia tested intranasal zinc gluconate against a placebo nasal spray in nearly 100 patients who were inoculated with a rhinovirus. Patients were pretreated for 3 days prior to inoculation and for 6 days thereafter. The infection rate with placebo (74%) was the same as that with zinc gluconate (78%). There was also no difference in symptomatology including rhinorrhea, nasal obstruction, or other upper respiratory symptoms associated with use of zinc (Clin Infect Dis. 2001;33:1865-1870).
The FDA has approved a new Factor Xa inhibitor for the prevention of postoperative deep venous thrombosis (DVT). Fondaparinux sodium (Arixtra) is approved for use after orthopedic procedures including hip fracture, hip replacement, and knee replacement. The drug is the first of the new class of agents designed to inhibit Factor X. The approval was based on randomized double-blind trials involving more than 4000 patients who had undergone orthopedic surgery. The drug is contraindicated in patients weighing less than 50 kilograms and those with severe renal impairment. It is also contraindicated in patients who have received spinal anesthesia or had a recent spinal puncture.
An intranasal steroid along with antibiotics improves success rates and speeds recovery in the treatment of rhinosinusitis. Researchers from North Carolina looked at 95 patients with a history of chronic rhinitis or recurrent sinusitis and evidence of an acute infection. All patients were treated with cefuroxime 250 mg twice daily for 10 days, along with the nasal decongestant for 3 days. Half the patients were randomized to fluticasone propionate nasal spray or placebo nasal spray in each nostril once per day for 3 weeks. Patients were followed-up for 2 months. Patients receiving fluticasone improved more rapidly and achieved a significantly higher rate of clinical success than patients receiving placebo. The study recommends consideration of intranasal steroids as part of the therapeutic regimen for treatment of acute sinusitis in the patient with a history recurrent or chronic sinus infections (JAMA. 2001;285:3097-3105).
A new study gives guidance as to which menopausal women will benefit more from hormone replacement therapy (HRT) or the selective estrogen receptor modulator raloxifene. Researchers at Penn used a time-dependant Markov model to estimate the life expectancy using either modality. These findings suggest women who are at average risk for breast cancer and coronary heart disease may benefit more from HRT, while women with one or more major breast cancer risks will benefit more from raloxifene. This study assumes a 20% or higher reduction in the risk of CAD with HRT (Obstet Gynecol. 2001;98:996-1003).
Dr Elliott is the Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr Elliott is Editor-in-Chief of The Physician's Therapeutics & Drug Alert.