Is There a Role for the New Oral Agents in VTE Prophylaxis in 2012?

Jeffrey Gollish, BASc, M.D., FRCSC
Medical Director, Head of Arthroplasty Program
Holland Orthopaedic and Arthritic Centre
Sunnybrook Health Sciences Centre
Toronto, ON

Is there a role for the new oral agents in VTE prophylaxis in 2012? The answer is unequivocally, yes.

It appears to be well accepted amongst Canadian orthopaedic surgeons that patients undergoing hip or knee arthroplasty are at significant risk for VTE. In the last report of the Canadian Joint Replacement Registry, prior to the introduction of the new oral agents in 2008, 98% of the reporting orthopaedic surgeons indicated that they routinely used either LMWH or warfarin for VTE prophylaxis for their arthroplasty patients.

 

Prior to 2008, the only oral anticoagulant agent available was warfarin, which had been introduced to the market approximately 70 years prior. The necessity for regular PT/INR monitoring, as well as significant reductions in post-surgical lengths of stay, resulted in reduced acceptability of this agent, despite its convenience as an oral (as opposed to an injectable) agent. More than two decades ago, LMWHs were introduced and the randomized trials demonstrated both efficacy and safety in VTE prophylaxis. These eventually became the "gold standard" and prior to 2009 were the agents of choice for approximately 78% of orthopaedic surgeons for VTE prophylaxis.

Since 2008, three new oral agents have been approved for use in Canada (rivaroxaban, dabigatran and apixaban). The randomized phase 3 trials of these agents have demonstrated, in the majority, either superior or non-inferior efficacy in comparison to LMWHs and non-inferior safety with respect to all-cause mortality and major bleeding.

The primary concern expressed by the orthopaedic community in relation to the introduction of the new oral agents has been the potential for increased major bleeding and wound complications. Interestingly, these were the same objections voiced at the time of the introduction of LMWHs, which then went on to be accepted by the majority as the agents of choice, as noted above.

At our institution, we introduced one of the new oral agents (rivaroxaban) in January 2009 and this has been the standard agent for VTE prophylaxis since then. All patients undergoing hip or knee arthroplasty surgery (both primary and revision) are prophylaxed with this agent unless there is a contra-indication as per the product monograph or are taking warfarin for atrial fibrillation. To date, we have used this oral agent in more than 6,000 patients and since June 2012, we have collected data on a prospective basis for three months post-surgery, and have captured data on 97% of the patients who have had surgery. Our DVT and PE rates at six weeks post-op have been 0.1 and 0.4% respectively, with major bleeding (both surgical site and non-surgical site) at 0.05% and we have had no deaths from PE. Since the introduction of this agent, in comparison to our prior agent (warfarin) we have not seen an increase in transfusion rates, infection rates or re-operation rates. Lengths of stay continue to decrease. Compliance with the protocol remains high post-discharge. The efficacy and safety profiles in our institution have been acceptable to both surgeons and patients alike.

The release of the ACCP recommendations for VTE prophylaxis in Chest Feb 20121 has resulted in increased controversy again with respect to the appropriate agents for VTE prophylaxis. The recommendations are different than those made in 2008 and raise a variety of issues including relative risk assessment for VTE, patient input into the VTE method chosen and the role of agents that previously have been considered less efficacious in reducing the event rates in VTE (unfractionated heparins, aspirin). In the UK, the NICE clinical guidelines 20102 made similar recommendations, aside from recommending against the use of aspirin. The common agents recommended for use by both groups included LMWH, fondaparinux, rivaroxaban, and dabigatran (apixaban not yet having been released in the UK at the time).

In summary, it remains for us as orthopaedic surgeons to be well informed of the relative risks and benefits of any treatment intervention which we undertake for our patients. With respect to VTE prophylaxis, the current Canadian community standard for hip and knee arthroplasty would appear to be the use of an agent that has proven efficacy and safety. Other important considerations include ease of adherence to the recommended protocol and acceptable cost. The new oral agents clearly fit this profile. The above-mentioned standard is strongly supported by the Canadian Patient Safety Institute and excellent information is available at the Safer Health Care Now web site.

References

 

  1. CHEST 2102 Feb; 141(2Suppl):e278s-325s
  2. NICE clinical guideline 92 - Jan 2010

Submit Community Content

If you have orthopedic information that you would like to share with the Orthogate Community, please register/login and submit your news, event, job, article, case or workshop from the Submit Content menu under the My Account area. Learn more!