December 22nd, 2010

Apixaban Beats Enoxaparin for Thromboprophylaxis After Hip Replacement

In the ADVANCE-3 trial 5,407 hip replacement patients were randomized to receive thromboprophylaxis with either the new oral factor Xa inhibitor apixaban or enoxaparin. The rate of DVT, nonfatal PE, or death from any cause was 1.4% in the apixaban group compared to 3.9% in the enoxaparin group (RR 0.36, CI 0.22-0.54, P<0.001), thereby demonstrating both noninferiority and superiority of apixaban. The rate of major and clinically relevant nonmajor bleeding was 4.8% with apixaban and 5.0% with enoxaparin.

In an editorial accompanying the article (and also accompanying the appearance in print of the EINSTEIN-DVT trial), Elaine Hylek writes that “the oral factor Xa inhibitors represent a major advance in the prevention and treatment of thromboembolic disease.” But Hylek cautions that results with these agents in the real world may not be quite as rosy as in the clinical trials: “Because both the risk of thrombosis and the risk of hemorrhage increase substantially with age and with burden of chronic disease, the effectiveness of the novel agents in real-world practice will need to be closely monitored, particularly among older adults with renal impairment.”

2 Responses to “Apixaban Beats Enoxaparin for Thromboprophylaxis After Hip Replacement”

  1. Leon Hyman, Ms M.D. says:

    NO one has discussed the personal cost to patients in their glowing endorsements of the Xa oral inhibitors. coumadin’s out of pocket expense to a patient with prescription insurance is at most $4.00 for a 30 day supply. When they have to pay $50.00 or more per month for the Xa inhibitors, it may be hard to get them to switch especially if they have been well controlled on warfarin. Also, as the Medical Letter on drugs and therapeutics loves to point out, the long term possible hidden side effects of the Xa inhibitors remains to be seen.

    Competing interests pertaining specifically to this post, comment, or both:

  2. Rahul Bhardwaj, MD says:

    Dr. Hyman,

    There has been a cost-analysis of dabigatran by a group from Stanford published in Annal of Internal Medicine. Freeman et al. Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation; Ann Intern Med. 2010 Nov 3. The incremental cost-effectiveness ratio compared with warfarin was $45,372 per quality-adjusted life-year for high-dose dabigatran at the cost was $13.70 per day. The cost set by the company to wholesalers is $6.75 per day (Dec 1 CardiologyToday article).

    According to some articles, ICDs have been estimated to have an incremental cost-effectiveness ratio of $34,000-$70,000, so the figure is not unreasonable.

    With all that said, I agree that cost to the patients is a factor and hopefully with more drugs on the market (rivaroaban, apixaban), prices will be driven down further.

    We will see what happens with regards to hidden side effects…. Recently, a more intensive analysis of the RE-LY data was released and found relative risk for stroke / embolic events to be 0.65 (95% CI 0.52-0.81; p<0.001). RR for major bleeding was non-significant at 0.93 (95% CI 0.81-1.07). Risk of MI was also nonsignificant: RR 1.27 (95% CI 0.94-1.71; p=0.12). This is somewhat encouraging, but only time will tell!

    Competing interests pertaining specifically to this post, comment, or both: