ShortCuts-This Week in the Journals

June 30, 2008

pitons.jpgCommentary by Danise Schiliro- Chuang MD

Welcome to the wide world of shortcuts. While I hope this post comes to you from your laptop while you’re relaxing on the beach with a cool drink, I realize this is likely not the case. Hopefully, reading this post will be refreshing enough.

Also before we start, a warm welcome to the new intern class! We hope that you’re settling in to life as an MD with ease and that you will enjoy shortcuts for years to come. Let’s get started!

Last week, the American College of Chest Physicians (ACCP) published updated evidence-based guidelines addressing the prevention and management of thrombosis. Developed by an international panel of 90 experts, these guidelines include more than 700 recommendations related to the prevention and management of thrombotic disorders. While I thought it would be fun to go through all 700 recommendations, I decided to choose a few highlights. For all of our new interns wondering who should get venous thromboembolism (VTE) prophylaxis, the guidelines recommend it for most patients. However, they do not recommend routine use for patient groups with a very low risk of VTE. This includes patients undergoing laparoscopic surgery, knee arthroscopy, or those who take long airplane flights. The guidelines continue to recommend against the use of aspirin alone for VTE prophylaxis in any population.

Several specialized populations are addressed in the new guidelines, including those undergoing surgery. A full chapter is dedicated to the perioperative management of patients on long-term antithrombotic therapy who require surgery or other invasive procedures. Most patients must temporarily stop anticoagulation just prior to undergoing surgery in order to minimize bleeding; however, this can increase the risk of a thromboembolic event. To address this challenge, the guidelines recommend that the risk of a thromboembolic event during interruption of therapy be balanced against the risk for bleeding when antithrombotic therapy is discontinued. The guidelines also recommend routine use of VTE prophylaxis for patients undergoing major general, gynecologic, or orthopedic surgeries and have been expanded to include bariatric and coronary artery bypass surgery.

Also specifically addressed in the new guidelines are challenging issues facing women who are pregnant or wish to become pregnant while undergoing long-term antithrombotic therapy. Pregnant women taking vitamin K antagonists (VKAs) such as warfarin have an increased risk for birth defects and miscarriage. For most women taking VKAs who become pregnant, the guidelines recommend substituting low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) and suggest frequent pregnancy tests and the substitution of LMWH or UFH once pregnancy is achieved. For women with mechanical valves who become pregnant, the guidelines suggest either adjusted-dose bid LMWH or UFH throughout pregnancy or adjusted-dose bid LMWH or UFH until the thirteenth week with VKA substition until LMWH or UFH are resumed close to delivery. In pregnant women with high-risk mechanical valves (i.e., older-generation valve in the mitral position or history of thromboembolism), the use of oral anticoagulants over heparin is suggested because of concerns about the effectiveness of alternative anticoagulants in preventing stroke and valve thrombosis.

Remember, this is just a teaser. If you’re still interested or have a management question about a patient, check out the full set of guidelines.

Keeping with the theme of anticoagulation, this week’s NEJM gives us 2 randomized, double-blind, placebo-controlled trials comparing the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus enoxaparin, a LMWH, in preventing VTE after 2 orthopedic surgeries. Current options for extended VTE prophylaxis are limited to LMWH, which must be administered subcutaneously, and VKAs such as warfarin, which have unpredictable pharmacologic effects, numerous food and drug interactions and require frequent laboratory monitoring. One can begin to see the possible advantages, both for the doctor as well as patient, of giving a once daily, oral medication that does not need lab monitoring.

The first study, by Eriksson and Borris et al, compared rivaroxaban with enoxaparin for extended VTE prophylaxis in patients undergoing total hip arthroplasty. About 4500 patients were assigned to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery. The primary efficacy outcome was the composite of DVT (either symptomatic or detected by bilateral venography), nonfatal pulmonary embolism, or death from any cause at 36 days. This outcome occurred in 1.1% in the rivaroxaban group and 3.7% in the enoxaparin group, a significant difference with an absolute risk reduction (ARR) of 2.6% and a number needed to treat (NNT) of approximately 38. The secondary outcome, major VTE, occurred in 0.2% in the rivaroxaban group and 2.0% in the enoxaparin group, also a significant difference with an ARR of 1.7% and a NNT of approximately 59. The primary safety outcome, major bleeding, was rare and similar in both groups.

The second trial, authored by Lassen and Ageno et al, compared rivaroxaban with enoxaparin in preventing VTE after total knee arthroplasty. This study assigned approximately 2500 patients to receive either 10mg of oral rivaroxaban once daily, beginning 6 to 8 hours after surgery, or subcutaneous enoxaparin, 40 mg once daily, beginning 12 hours before surgery. The primary outcome was again the composite of any DVT, nonfatal pulmonary embolism, or death from any cause within 13 to 17 days after surgery. This outcome occurred in 9.6% who received rivaroxaban and 18.9% who received enoxaparin, a significant difference with an ARR of 9.2% and NNT of around 11. Major VTE, a secondary outcome, occurred much less often: 1.0% of patients given rivaroxaban and 2.6% of patients given enoxaparin. This difference remained significant with an ARR of 1.6% and NNT of around 63. Safety profiles were again similar.

While longer follow-up data will likely be needed to assess efficacy and safety, this new drug shows promise for VTE prophylaxis following these orthopedic procedures that are frequently complicated by post-operative thrombotic events.

Finally, let’s switch gears a bit. This week, the CDC released 2007 prevalence data on a disease familiar to us all: diabetes. According to this report, nearly 24 million people (around 8% of the population) in the U.S. had diagnosed diabetes in 2007, while another 57 million people have pre-diabetes. While the number of cases of diagnosed diabetes represents an increase of greater than 3 million cases since 2005, the data also show that the number of people who do not know they have diabetes has decreased over the past 2 years. This indicates the increase in cases is likely an overestimation and that we’re doing a better job of diagnosing diabetes. In terms of subgroups, the report states that diabetes continues to disproportionately affect the elderly, with almost 25 percent of the population ≥ 60 years having diabetes in 2007. In addition, racial disparities continue to exist, with the rate of diagnosed diabetes being highest among Native Americans and Alaska Natives followed by blacks and Hispanics. When estimates were broken down for all counties in the United States, increased diabetes rates were seen in areas of the Southeast and Appalachia, areas recognized in the past as being at higher risk for many chronic diseases. As the CDC funds diabetes prevention and control programs throughout the U.S., knowing where the disease is most prevalent and who is most affected will enable the organization to properly allocate their funds to these specific communities.