Panel says no to rivaroxaban for ACS

July 15, 2012

FDA says no to rivaroxaban for ACS. ACCP updates DVT evidence. Fatal bleeds from dabigatran have tapered off

This decision was based largely on concerns about early patient withdrawals and missing data. About 12% of patients in the ATLAS ACS 2 trial had incomplete follow-up, and a total of 1,294 subjects discontinued the trial prematurely. The company was only able to contact 183 patients who dropped out, of whom 177 were confirmed to be alive. It adopted a "modified intention-to-treat analysis" because of these patient dropouts. This meant that patients were observed for 30 days after randomization or the global end date for the trial, instead of observing all the patients until the end of the trial as FDA had first suggested.

One of the FDA reviewers, the medical team leader, had previously stated that "because of the extent of missing follow-up in ATLAS we cannot have confidence in either the calculated mortality or CV end point benefits." Other issues raised included concerns about the shorter time for follow-up, given that these patients may be likely to experience events outside of a 30-day window.

2012 ACCP guidelines update DVT evidence

Venous thromboembolism (VTE) associated with air travel was first described in the early 1950s. Previous studies have shown a 2- to 4-fold increased risk of VTE after air travel. In 2001, the World Health Organization (WHO) set up the WHO Research into Global Hazards of Travel (WRIGHT) project, a large collaborative research study to confirm the association between VTE and air travel. This study and others regarding this issue have been inconclusive. Although developing a travel-related deep venous thrombosis (DVT)/VTE is unlikely in most cases, the updated 2012 American College of Chest Physicians (ACCP) guidelines note that for long-distance flights, several factors may increase an individual's risk of developing a DVT/VTE.

These risk factors include previous DVT/VTE or known thrombophilic disorder; active malignancy; recent surgery or trauma; immobility; estrogen use or pregnancy; advanced age; severe obesity; and sitting in a window seat. For travelers with an increased risk for travel-related DVT/VTE, the guidelines recommend frequent ambulation, calf muscle stretching, sitting in an aisle seat if possible, or the use of below-knee graduated compression stockings.

The ACCP guidelines suggest there is no definitive evidence to support that alcohol intake, dehydration, or sitting in economy class increases a patient's risk for developing a DVT/VTE resulting from long-distance flights. A patient's risk should be carefully evaluated before recommending prophylaxis for VTE.

Sources: Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e1955-e2265; New guidelines suggest DVT prophylaxis not appropriate for all patients. February 7, 2012. http://www.chestnet.org/accp/article/new-guidelines-suggest-dvt-prophylaxis-not-appropriate-all-patients/. Accessed June 4, 2012.

Dabigatran fatal bleeding now lower since approval

The European Medicines Agency (EMA) has reported that the frequency of fatal bleeding with dabigatran has been significantly lower since the drug's approval than what was observed in clinical trials. The EMA's Committee for Medicinal Products for Human Use came to this conclusion after an in-depth (not yet released) review of these events was performed. Despite this conclusion, the committee decided that certain recommendations for prescribers and patients should be clarified and strengthened by adding further information regarding situations in which the drug should not be used and management of emergencies.

Their review was initiated in January 2012, following reports of bleeding with dabigatran from across the globe. The review considered available data on risk of serious or fatal bleeding with dabigatran from both the clinical trials that supported its approval and postmarketing surveillance.

Sources: Dabigatran fatal bleeding less than in clinical trials. May 25, 2012. http://www.theheart.org/article/1406229.do?utm_campaign=newsletter&utm_medium=email&utm_source=20120528_EN_Heartwire/; European Medicines Agency. European Medicines Agency updates patient and prescriber information for Pradaxa. May 25, 2012. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/05/news_detail_001518.jsp&mid=WC0b01ac058004d5c. Accessed June 4, 2012.

Anna D. Garrett is a clinical pharmacist and president of Find Your Best Thinking, a health and wellness coaching company. Contact her at anna@findyourbestthinking.com
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