Vioxx Might Control Postoperative Knee Pain
Pharmacology Watch

Oral rofecoxib (Vioxx) may have a role in controlling postoperative pain patients undergoing knee surgery. Researchers in Chicago enrolled 70 patients who were undergoing total knee arthroplasty and randomized them to rofecoxib 50 mg the day prior to surgery, 1-2 hours prior to surgery, and for 5 days postoperatively, then 25 mg daily for another 8 days; or matching placebo at the same times. The main outcome was postsurgical analgesic consumption and pain scores, as well as nausea and vomiting, joint range of motion, sleep disturbance, and patient satisfaction with analgesia and hematologic anticoagulation parameters. Rofecoxib resulted in significantly reduced use of epidural analgesia and in-hospital opioid consumption (P < .05). Pain scores were also lower in the rofecoxib group while in the hospital (P < .001) as well as 1 week after discharge (P = .03). Rofecoxib also resulted in less postoperative nausea, a decrease in sleep disturbance, as well as increased knee flexion at 1 month—including a shorter time in physical therapy to achieve effective joint range of motion. The drug had no effect on warfarin usage or INR levels postoperatively. Interestingly, Buvanendran and colleagues did not include changes in renal function or evidence of GI intolerance in the study analysis. They did conclude however that rofecoxib is effective at reducing postoperative pain and opioid consumption after major orthopedic surgery (JAMA. 2003;290:2411-2418).

Echinacea Has No Value for URIs

Just in time for winter, another study showed that Echinacea has no value for reducing the duration or severity of upper respiratory tract infections (URIs). The herbal remedy is commonly used worldwide for this indication. In this study of children in the Pacific Northwest, 707 URIs occurred in 407 children over 2 years. Three hundred thirty-seven URIs were randomized to treatment with Echinacea while 370 were assigned to placebo. Echinacea was begun at the onset of symptoms and continued throughout the infection for maximum of 10 days. Data analysis showed there was no difference in the duration of URIs with Echinacea or placebo (P = .89), and there was no difference in the overall estimate of severity of URI symptoms (P = .69). There was also no statistically significant difference between the 2 groups for peak severity of symptoms, number of days of peak symptoms, number of days of fever, or parental global assessment of severity of URI. Rash occurred during 7.1% of URIs treated with Echinacea and 2.7% of those tree with placebo (P = .008). The study concludes that Echinacea was not effective in treating URI symptoms in patients 2 to 11 years old but was associated with an increase in skin rash (JAMA. 2003;290:2824-2830).

Valsartan, Captopril Have Similar Benefits

Valsartan and captopril have similar benefits in patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both, according to a new study. Previous studies have shown that ACE inhibitors reduce mortality and cardiovascular morbidity in this group, but it was unclear if angiotensin receptor blockers (ARBs) conveyed the same benefit. In this international study, nearly 15,000 patients with myocardial infarction were randomized to valsartan, captopril, or a combination of valsartan and captopril. The primary end point was death from any cause. The median follow-up was just more than 2 years. During that time, the death rate in all 3 groups was remarkably similar (979 of 4909 deaths valsartan, 958 of 4909 deaths captopril, 941 of 4885 deaths combination [hazard ratio valsartan vs captopril 1.0; 97.5% CI, 0.9-1.11; P = 0.98], [hazard ratio valsartan and captopril vs captopril, 0.98; 97.5% CI, 0.89-1.09; P = 0.73]). The valsartan plus captopril group had the most drug-related adverse events, while in the monotherapy groups valsartan was associated with more hypotension and renal dysfunction, while cough, rash, and taste disturbance were more common with captopril. Pfeffer and associates conclude that valsartan is as effective as captopril in patients with myocardial infarction who are at high risk for cardiovascular events, but combining valsartan with captopril did not offer an advantage (N Engl J Med. 2003;349:1893-1906).

In-patients Likely to Continue Lipid Use

In-patients who are started on lipid-lowering therapy following coronary intervention are 3 times more likely to continue on the drugs compared to patients who are started on the same therapy as outpatients. Using data from the EPILOG trial in which patients underwent percutaneous coronary intervention for stable or recently unstable coronary artery disease, 175 patients were discharged from the hospital on lipid-lowering therapy and 1951 were discharged on no lipid-lowering therapy, with the intent to start them on treatment as outpatients. After 6 months of follow-up, 77% of patients who were started in the hospital were still taking lipid-lowering therapy compared with only 25% of those who were discharged without lipid-lowering therapy (P < .001). Aronow and colleagues suggest that initiation of lipid-lowering therapy in the hospital is effective strategy to enhance subsequent use of the drugs in these high-risk patients (Arch Intern Med. 2003;163:2576-2582).

More on Metformin/Lactic Acidosis

When it comes to the relationship between metformin and lactic acidosis, the emperor may have no cloths. The drug, which has been used to treat type 2 diabetes for more than 40 years, has always carried with it the stigma that it may cause lactic acidosis in at-risk patients. Metformin hydrochloride is a biguanide that is similar in structure to phenformin hydrochloride, which was withdrawn from the market because of a documented risk of lactic acidosis. Metformin increases glucose oxidation without substantially affecting fasting lactate production and peripheral tissues unlike phenformin, and the true rate of metformin-associated lactic acidosis has never been demonstrated. Recently, researchers from Stanford performed a thorough review of the literature on this topic and performed a meta-analysis on 194 studies involving nearly 37,000 patient years in the metformin group and 30,000 patient years in the nonmetformin group. No cases of fatal or nonfatal lactic acidosis were found in either group. Their conclusion is that there is no evidence that metformin therapy is associated with an increased risk of lactic acidosis or with increased lactate levels compared with other antihyperglycemic treatments (Arch Intern Med. 2003;163:2594-2602). The study is important because metformin is an effective treatment for type 2 diabetes, and has some unique properties including stabilizing weight gain or even facilitating weight loss. The drug has also recently become multisource (generic) and is affordable for diabetic patients who must pay for their medications.

FDA Notes

The FDA has approved tadalafil (Cialis), Eli Lilly and Icos Corp’s entry into the lucrative phosphodiesterase inhibitor market. With the success of sildenafil (Viagra), and newcomer vardenafil (Levitra) already generating huge profits, Cialis is being touted as a longer acting, less expensive alternative for the treatment of erectile dysfunction. The drug, which exerts its effect over 36 hours, has already been dubbed "the weekend drug" in Europe, where it as been available for some time.

Bristol-Myers has received approval to market the first chewable oral contraceptive for women. The product is a new formulation of Ovcon 35 (norethindrone and ethinyl estradiol), which is spearmint flavored and can be chewed or swallowed whole. If chewed than swallowed, the woman should drink a full 8 oz of liquid immediately afterward to make sure the entire dose reaches the stomach.

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. Telephone: (404) 262-5517. E-mail: 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.