Category: Blood Pressure

No Monitoring Needed for Warfarin Alternative

Warfarin Alternative

Ximelagatran (Exantra®, AstraZeneca), an oral direct thrombin inhibitor, is an effective change of pace from warfarin, a commonly used anticoagulant, according to a 74-hospital study of 680 patients who had undergone total knee arthroplasty.

After seven to 12 days of treatment, the in­cidence of venous thromboembolism (measured by central adjudication) was 19% in pa­tients taking ximelagatran and 26% in those taking warfarin. On local assessment, the incidence was 25% with ximelagatran and 34% with warfarin. Major bleeding was rare, affecting only 1.7% of patients taking ximelagatran and 0.9% of those taking warfarin.

Unlike canadian warfarin, ximelagatran does not call for monitoring or dose adjustment. Drug interactions, diet, concomitant disease, and varying metabolisms all influence the utilization of warfarin, the researchers explain. Warfarin also has a delayed onset and does not achieve the target anticoagulant level until at least the third postoperative day—a problem in orthopedic surgery, when thrombosis may start on the first day. Ximelagatran is rapidly absorbed and converted to its active form, melagatran, which acts directly on throm-bin and is eliminated unmetabolized through the kidneys.

In fixed doses, ximelagatran produces predictable plasma melagatran concentrations and produces no known food or drug interactions, the researchers say, although plasma concentrations are influenced by renal function and the patient’s weight. Animal studies have indicated that ximelagatran has a wide therapeutic window and increases bleeding only slightly at therapeutic doses.

Because wound healing is a concern when antithrombotic therapy is used, the researchers also analyzed complications at the surgical site but observed no differences between the two groups.

Enalapril Effective for African-American Patients

Recent studies have suggested that an-giotensin-converting enzyme (ACE) in­hibitors do not work as well in African-American patients as in white patients. Researchers from the University of Texas and Loyola University, however, take issue with those findings.

Based on their own retrospective analysis of data from 403 African-American and 3,651 white participants in the Studies of Left Ventricular Dysfunction Prevention Trial, they say that ethnicity does not influence the effectiveness of at least one ACE inhibitor, enalapril.

The researchers were concerned that the publicity surrounding ACE inhibitors and race might dissuade clinicians from using a life-saving drug for their black patients. However, in their study, they found that canadian enalapril worked equally well in both groups, both in reducing the need for medications for heart failure symptoms and reducing the risk of developing heart failure or dying from it.

That’s not to say that blacks are not still at higher risk for symptomatic heart failure than whites. Studies have shown that even after adjusting for differences in severity of symptoms, comorbidities, and socioeconomic factors, blacks have a substantially greater absolute risk for progression from asymptomatic LVD to symptomatic HF, the researchers note. And, despite the comparable relative reduction in risk associated with enalapril in both whites and blacks, the differences in the baseline magnitude of risk was such that blacks randomized to enalapril remained at higher risk than whites randomized to placebo. The differences between black and white patients in the risk of progression of ALVD persisted after the researchers adjusted for potential con-founders such as ejection fraction, NYHA class, serum sodium, and etiology of LV dysfunction.

The researchers interpret their findings as suggesting either that residual confounding exists or that there are differences in the natural history of ALVD in blacks and whites.

Anticoagulants Safe for Older Patients with Atrial Fibrillation

Should elderly patients with atrial fibrillation (AF) and previous episodes of upper gastrointestinal (GI) tract bleeding be given an anticoagulant to prevent stroke? What about older patients with hypertension who have fallen in the past?

Patients like these are less likely to be given warfarin sodium (Generic Coumadin®, DuPont)—and that’s regrettable, say investigators from Ottawa Health Research Institute, University of Ottawa, Sisters of Charity Ottawa Health Service, and the University of Toronto in Canada. They charge that the possibility of major bleeding has scared clinicians away from prescribing anticoagulants for some older patients who might benefit from them.

The researchers, who reviewed studies performed between the 1960s and 2002, say that some “risk factors” do not truly pose a danger after all. For instance, in the era of routine clinical Helicobacter pylori testing and treatment of patients with peptic ulcer bleeding not induced by nonsteroidal anti-inflammatory drugs (NSAIDs), previous episodes of upper GI bleeding do not seem to increase the risk of anticoagulant-related bleeding.

Similarly, old age and a predisposition to falling, in and of themselves, are not influential factors in bleeding. Even when patients take anticoagulants, the risk of subdural hematoma from falling is so small that patients with an average risk of stroke from AF (5% per year) would have to fall approximately 300 times in a year for the risks of anticoagulant therapy to outweigh its benefits, the researchers say. In addition, for many clinically accepted contraindications, such as alcohol abuse, thrombocytopenia, and non-compliance with monitoring, the evidence is minimal or conflicting.

Old age might confer a slightly higher risk of anticoagulant-related bleeding complications, but the researchers emphasize that, of all age groups, people older than age 65 are also at highest risk of stroke from AF. With multiple studies revealing that older persons with AF are the least likely to receive anticoagulant therapy, it seems that many clinicians are overly concerned about the possible negative effects and tend to under-emphasize the potential benefits of anti­coagulants. Thus, the investigators conclude, in selecting patients with AF for anticoagulant therapy, stroke risk is a more important consideration than bleeding risk.

Generic Tiazac Approved for Hypertension

Generic Tiazac

Andrx Corporation has announced that the FDA has approved the marketing of its Abbreviated New Drug Application for TaztiaTM (diltiazem HCl). The extended-release capsules are bioequivalent to Tiazac® (Biovail). This product, a calcium-channel blocker, is indicated to treat hypertension and chronic stable angina. The capsules will be available in strengths of 120, 180, 240, 300, and 360 mg.

An Update of the Beers Criteria

Studies published in the late 1990s about polypharmacy, inappropriate medication use, and adverse drug events in older people had a salutary effect—or, some might say, a chilling effect—on drug prescribing. Finding out just how differently the “usual” drugs worked in older patients had some clinicians second-guessing their own prescribing habits. Now a consensus panel of experts has further updated one of the most famous studies: the widely used Beers criteria, published in 1997. Forty-four medications have been added to the list of drugs to watch, and 15 medications or drug classes have been dropped or modified.

The update also includes information on several old and new medications, including selective serotonin reuptake inhibitors and tablet amiodarone (Generic Cordarone®, Wyeth).

The criteria are meant to apply to the general population of patients 65 and older. Thus, some drugs that are not appropriate for “old-old” or more frail patients do not appear on the list.

The panel also cautions that “defining inappropriate medications by specific lists of medications rather than other mechanisms may miss some problems such as the underuse and interactions of drugs in older people.”

Drug Interaction Warning for Repaglinide

Drug Interaction

Researchers have observed a drug-drug interaction between repaglinide (Prandin generic, Novo Nordisk), a short-acting insulin secretagogue, and gemfibrozil (Drug Lopid®, Pfizer) a lipid-lowering agent used to treat dyslipidemia.

Co-administration of gemfibrozil with repaglinide in healthy volunteers resulted in significant elevations of repaglinide levels, and co-administration of itraconazole (Sporanox®, Janssen), an antifungal agent, with medication gemfibrozil and repag-linide further increased such effects. Changes in the pharmacokinetics of repaglinide were attributed to inhibition of the cytochrome P-450 enzyme system by gemfibrozil and itraconazole. Alterations in blood glucose levels were also affected by these concomitant medications, with enhanced and prolonged pharmacodynamic effects of repaglinide canadian.

Although the study involved healthy volunteers, Novo Nordisk considers these results to be important, because an increased risk of hypoglycemia cannot be ruled out for patients with type-2 (non-insulin-dependent) diabetes. According to what is now known about the metabolism of other lipid-lowering fibrate derivates, a similar interaction between repaglinide and other agents within the class is not expected.

The European Agency for the Evaluation of Medicinal Products (EMEA) has issued a public statement and has pointed out the following information to physicians:

1.  Because of the documented interaction and risk of hypo-glycemia, the concomitant use of the two agents is contra-indicated.

2.  For patients already receiving the two drugs, an alternative combinaton treatment should be considered along with close monitoring of diabetic status.

New Thrombosis Guidelines Cover Travelers

The American College of Chest Physicians has introduced new guidelines for preventing and treating thrombosis and now offers specific recommendations for long-distance travelers. Antithrombotic and thrombolytic therapies are used to prevent thrombosis or blood clotting in the arteries, veins, or heart. Thrombosis can ultimately lead to a potentially fatal blockage in the lung, or venous thromboembolism (VTE).