The American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST) will be hosting their Fifth Joint American Transplant Meeting, the 2004 American Transplant Congress Meeting on May 15 – May 19, 2004. This year the meeting will be held in Boston, Massachusetts, where the first successful solid-organ transplant was performed 50 years ago. This meeting serves as a forum for the exchange of scientific and clinical information, ideas, and opinions for those who are interested in the research aspects of solid-organ and tissue transplantation. Physicians, surgeons, scientists, nurses, organ procurement personnel, and pharmacists attend workshops and meetings, present abstracts and posters, as well as participate in group sessions in an effort to examine and discuss issues and objectives that are relevant to organ and tissue transplantation. This meeting will be held at the Hynes Convention Center in Boston, MA. For more information, contact the American Transplant Congress 2004 staff at (856) 439-0880, or visit their web site at www.atcmeeting.org.

ACE Inhibitors vs. Angiotension Receptor Blockers Post Myocardial Infarction

It has been established that angiotensin-converting-enzyme (ACE) inhibitors reduce the risk of death as well as the risk of major non-fatal cardiovascular events after myocardial infarction. The patients who have benefited the most from ACE-inhibitor therapy are those with left ventricular dysfunction, signs or symptoms of heart failure, or both. Since angiotensin-receptor blockers (ARBs) block the activity of angiotensin II more completely than ACE inhibitors, several studies were conducted to investigate if there are greater clinical benefits with ARBs than ACE inhibitors or if a combination of the two might be most efficacious.

The OPTIMAAL trial was designed to test the hypothesis that losartan, an ARB, would be superior or non-inferior to captopril (ACE inhibitor) in decreasing all-cause mortality in high-risk patients after acute myocardial infarction. This trial showed no statistical difference between the captopril 50 mg three times daily (n=2733) and the losartan 50 mg daily (n=2744) in preventing all-cause death post-MI in high-risk population. Losartan was significantly better tolerated with fewer patients discontinuing study medication for any reason (p<0.0001). Many clinicians and researchers commented that some problems with the OPTIMAAL trial include inadequate dosage and slow rate of titration of losartan. For more information about this study, refer to Dickstein K et al. Lancet 2002;360:752-760.

Omeprazole reaches peak plasma concentrations in 0.5 - 3.5 hours, has a plasma half-life of 0.5 - 1 hour, and is 95% protein bound. It is approximately 77% eliminated in the urine as metabolites with the remainder being biliary excreted. Prilosec OTC® is recommended specifically for frequent heartburn, which is heartburn two or more days a week. Dosing is a once daily 20 mg tablet that treats heartburn for 24 hours as part of a 14-day course of therapy. Prilosec OTC® should be taken daily for 14 days to ensure proper treatment of frequent heartburn. Treatment should not be repeated for 4 months after use. Tablets should be swallowed whole; do not chew or crush tablets.

The VALIANT trial was designed to compare the effect of valsartan, an ARB, captopril, and the combination of the two on mortality among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. This trial showed that the ARB valsartan 160 mg twice daily (n=4909) is at least as effective as captopril 50 mg three times daily (n=4909) in reducing the risk of major cardiovascular events. The proportion of patients who were still taking the study medication after one year was highest in the valsartan group; valsartan was better tolerated than captopril with fewer patients discontinuing study medication (p<0.07). However, there was a significantly higher rate of serious adverse events (hypotension and renal problems) in the valsartan group over the captopril group. A combination of the two drugs was also tested, and these patients (n=4885) had a significantly lower rate of hospitalization for heart failure or MI than did other patients (p<0.007). However, combination therapy also resulted in more adverse events, such as hypotension, that led to dose reduction or discontinuation of study medication than did monotherapy. For more information about this study, refer to: Pfeffer MA et al. NEJM 2003;349:1893-1906.

In the January 2004 edition of Journal Watch, the following comments were made concerning ARBs and ACE inhibitors. “Basing their conclusions on these results and the proven record of ACE inhibitors, editorialists state that ACE inhibitors should remain the first-line treatment for patients who are at high risk after MI. However, ARBs appear to be as effective as ACE inhibitors, as long as comparable dosages are used. Combined therapy could be valuable for some patients, but more research is needed to delineate that subgroup.”

Authored by Lee A. Jenkins

New Medication Caduet®
(amlodipine besylate / atorvastatin calcium)

In February 2004, Pfizer, Inc. announced the FDA approval of its new dual therapy medicine Caduet® for the treatment of both hypertension and high cholesterol; it is the first medication to treat these two conditions in one pill. Caduet® is a combination of Norvasc® (amlodipine besylate), a calcium channel-blocker used to treat high blood pressure, and Lipitor® (atorvastatin calcium), an HMG-CoA reductase inhibitor used to treat high cholesterol.

Heart disease is the leading cause of death worldwide, and the two biggest risk factors for heart disease are high blood pressure and high cholesterol. It is estimated that 30 million people in the United States have both high blood pressure and high cholesterol, but less than 10% have achieved their recommended goal for blood pressure and cholesterol control. Additionally, patients who have both conditions account for 60% of all cardiovascular events (including myocardial infarction).

More than 3,700 patients with hypertension and high cholesterol were enrolled in the Caduet® clinical trial program. Recent research from the clinical studies indicates that Caduet® was well tolerated and many patients reached their target levels of blood pressure and cholesterol while taking Caduet®.

The most common adverse effects experienced with Caduet® include headache, weakness, dizziness, fluid retention, and abdominal pain, all characterized as mild to moderate. Caduet® is contraindicated in patients with active liver disease or unexplained elevations of liver functions tests. Since Caduet® does contain a “statin,” signs or symptoms that indicate serious adverse events, such as muscle pain or weakness, should be reported promptly and assessed. Caduet® has been administered with other antihypertensives including thiazide diuretics, beta-blockers, and angiotensin-converting-enzyme (ACE) inhibitors.

According to a Pfizer representative, Caduet® will be made available in the U.S. in the second quarter of 2004, and will be available in many different dosing combinations to allow for flexibility in dosing individual patients.

Authored by Lee A. Jenkins

Medication Access Program
University of Georgia at the
Medical College of Georgia
Clinical Pharmacy Program
CJ-1020
Augusta, Georgia 30912-2450
706-721-0131 or 800-736-2273 ext. 0131 or e-mail us at: map@mapuga.com