December 28th, 2012

FDA Approves Eliquis (Apixaban) for Stroke Prevention in AF

The FDA has finally approved apixaban (Eliquis, Bristol-Myers Squibb and Pfizer) to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). The action comes after the widely-anticipated drug had been plagued by delays at the FDA but well before the PDUFA deadline of March 17, 2013. Eliquis is the latest member of the new generation of oral anticoagulants, which also includes dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Johnson & Johnson).

The FDA said that apixaban should not be taken by patients with prosthetic heart valves or by patients with AF caused by a heart valve problem. (Recently the FDA added a contraindication to the dabigatran label against using the drug in patients with mechanical heart valves.) The FDA said that the most serious risk associated with apixaban, as with other anticoagulants, is bleeding, including life-threatening and fatal bleeding. Patients taking apixaban will receive a patient Medication Guide. The FDA is advising health care professionals to counsel patients about the signs of symptoms of possible bleeding.

The FDA approval was based largely on the results of the highly positive ARISTOTLE trial which found that apixaban was superior to warfarin in AF patients. It is not yet clear whether the FDA label will include a superiority claim for the drug. The FDA will likely allow Bristol-Myers Squibb and Pfizer to claim that apixaban is superior to warfarin, as the press release states that “patients taking Eliquis had fewer strokes than those who took warfarin.”

10 Responses to “FDA Approves Eliquis (Apixaban) for Stroke Prevention in AF”

  1. I am interested in who is going to jump in and start prescribing this medication. Many may want to sit on the sidelines with this medication until there is some more experience. Are there people in our community who are ready to prescribe this now?

  2. I’d say I am-for those folks where I am considering dabigatran or rivaroxaban- I don’t see a reason not to go with apixaban over those agents. Am i ready to move all my patients off warfarin-no-not until the reversal agent is worked out. But I do feel ready to prescribe this agent , where I have made the ecision to switch.

  3. Dan Hackam, MD PhD says:

    Definitely. Although the old maxim is never be the first or last physician to prescribe a new product, Apixaban, using indirect network analysis, beats riva and dabi hands down. Dabi has major problems with renal accumulation and GI toxicity (bleeding – primarily gastric; and dyspepsia, prompting discontinuation and poor adherence).

    Rivaroxaban was dosed incorrectly and was not superior to warfarin in ITT analyses; during interruption of the OD dosing due to transition to warfarin therapy, there was a very large spike in stroke/death (worrisome). This is bound to happen with temporary interruption of riva for procedures with OD dosing, unless patients are actively bridged (not generally recommended in NRAF patients). The terminal elimination t1/2 of this compound, as well as the marked peak-trough variability in anticoagulation status with OD dosing, clearly suggests it needs to be dosed BID like other class members. And the TTR in the defining trial was quite poor compared with the other studies (so we can see this compound at this dose is only about as “good” as warfarin when patients are in range a little better than half the time).

    On the other hand, apixaban actually beat warfarin for mortality and reduces bleeds in renal dysfunction compared with warfarin (stat. sig. interaction with renal function – Eur Heart J paper released simultaneously with ESC presentation of the data). There is no problem with dyspepsia and it was appropriately dosed in the trial. No issue with causing ACS either, and there are two very large defining trials (plus trials in other indications), whereas there is only one trial for each of the other competitive compounds.

    Have been prescribing dabigatran (not rivaroxaban) for quite some time now and have not seen any problems with it. I will definitely prefer apixaban once this compound is listed on formulary here – it seems to have hit the sweet spot of anticoagulation at the dosing regimen tested.

  4. Sergio Kaiser, M.D., PhD, F.A.C.C. says:

    Real life is different from controlled randomized clinical trials. This is a very promising drug, but I would rather wait some more time for post-marketing surveillance information. Here in Brazil, the new anticoagulants are being prescribed rather liberally for middle class consumers, even though pharmaceutic companies have made efforts to guide physicians toward appropriate prescription. What worries me most is the lack of an easy-to-find antidote such as vit K for warfarin.

  5. David Powell , MD, FACC says:

    I tried to prescribe it today, but the pharmacy did not have it. I share Dr. Hackam’s perspective. In AVEROES, there was no difference in serious bleeding compared with aspirin! ARISTOTLE shares RELY’s superiority ITT finding, and TTR was better than ROCKET.
    The only possible issue is that, unlike dabigatran, apixaban did not decrease ischemic stroke compared with warfarin. It’s stroke superiority lies in the lower hemorrhagic stroke rate.
    Now I will choose apixaban as my novel agent for older patients or those at higher bleeding risk. Otherwise, dabigatran. Rivaroxaban for those who can’t deal with twice daily dosing.

  6. I agree entirely with David Powell and will be using apixaban in a similar way. We do have a 110mg dose of Dabigatran licensed in the UK which I don’t believe is the case in the US though.

  7. Agree also with Dr. Powell-I do struggle with giving too much credit to dabi for the ischemic stroke issue given the open label design of RELY.

  8. Lorenz Van der Linden, PharmD says:

    In Belgium, we still await the reimbursement of Eliquis. The EC has already approved the AF indication, after positive advice from the CHMP. Yet, the company hasn’t received proper reimbursement for AF in Belgium (= so it won’t be prescribed because of the price).

    Speaking as a pharmacist, I suspect that it will be an attractive option for those patients with renal insuffiency (as is rivaroxaban), swallowing difficulties (rivaro is significantly absorbed in the stomach; dabi can’t be crushed) or a high bleeding risk, which comes down to our average elderly AF patients.

    NB: We currently see 50/50 rivaroxa/dabi in our hospital for AF, with more rivaroxa being used in the elderly AF patients.

  9. Jeff Dickey, MD says:

    The drug reps tell me there was a determination to limit the number of patients with CHADS2 scores of less than 2 in their trials, but not in the apixiban trials; does this introduce selection bias? In what way?

  10. Enrique Guadiana, Cardiology says:

    In Mexico we have apixaban, for the moment I don’t use it. They are appealing because routine monitoring is not requried but I always prefer to have the option to measure the anticoagulant effect. Quantitative tests for direct thrombin inhibitors and FXa inhibitors do exist, but they are not routinely available in most hospitals. I also want to have an antidote for the moment PCC, aPCC and rFVIIa don’t have enough clinical evidence. The pharmacodynamic interaction information is limited specialy with apixaban. Most of my patient with AF have coronary artery disease and in this context warfarin is superior. Short elimination half live and missing doses in the elderly is also a concern. I will wait.