From to ximelagatran to dabigatran - how far have we come?

I still remember the days when people thought ximelagatran was going to change the world of anticoagulation. The days of the Coumadin (warfarin) clinics seemed numbered. People who would require frequent INR checks would no longer have to get poked with needles. They could eat all the green vegetables they desire. They would no longer take rat poison. Then, the sad news about ximelagatran hit the news. Ximelagatran (proposed trade name Exanta) was not going to be approved by the FDA because of liver toxicity. That was 2006.

Fast forward now to 2010 and we see that the FDA advisory committee (not the FDA, but the FDA advisory committee) unanimously today recommended the approval of dabigatran. This means that the FDA will probably approve dabigatran in the near future, but we still need to wait and see. Meanwhile, a host of other new anticoagulant drugs are waiting in line.

So what are these new oral anticoagulants? Let's see what Wikipedia has to say:

• Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting) by directly inhibiting the enzyme thrombin. Agents in the pipeline include: dabigatran, melagatran (and its prodrug ximelagatran), and others.
• Direct factor Xa inhibitors ('xabans') are a class of antithrombotics which act directly upon Factor X in the coagulation cascade, without using antithrombin as a mediator. Agents in the pipeline include: rivaroxaban, apixaban, edoxaban, otamixaban, and others.

The landscape of oral anticoagulation is about to change if these new oral agents get approved by the FDA. What role will Coumadin (warfarin) play in all of this? Will we look back in 20 years and wonder how we managed patients on a drug like Coumadin? Will these new anticoagulants stand the test of time? What will happen to all the injectable agents like enoxaparin (Lovenox), certoparin (Sandoparin), tinzaparin (Innohep), dalteparin (Fragmin), and others?

Physicians will need to be more familiar with the pharmacological profiles (half-life, interactions, etc.) as they choose among the myriad of available agents when they're treating patients with atrial fibrillation, DVT, or PE. Hospitalized patients at risk for DVT may no longer need to suffer from multiple injections if they simply need to take a pill. These emerging agents may also be used for patients who have artificial heart valves, those who have other types of hypercoagulable disorders, and more.

Back in 2006, we thought we were going to see a revolution in anticoagulation management, but it didn't happen. Now, in 2010, it appears like we may truly be looking at a new era.

FDA Approves Generic Lovenox (Enoxaparin)

I still remember when Lovenox came out. Lovenox was the first low-molecular-weight heparin (LMWH) and it was a drug that changed the way anticoagulation was managed in the hospital setting. Instead of chasing PTT values and adjusting heparing drips, you could simply prescribe a fixed dose of an injection when treating patients who have a DVT or PE (pulmonary embolism).

Now, there's a generic form of this injectable blood thinner for patients who require anticoagulation therapy. Here's a snippet from a recent FDA press release:

The U.S. Food and Drug Administration today approved the first generic version of Lovenox (enoxaparin sodium injection), an anti-coagulant drug used for multiple indications including prevention of deep vein thrombosis (DVT), a potentially deadly blood clotting condition.

Approved for use in 1993, Lovenox is made from heparin, a blood-thinning drug whose active ingredient is a naturally-derived complex mixture of sugar molecules.

Every time a generic drug gets approved, I'm reminded that time passes by so quickly. In some ways, it feels like yesterday when the branded drug received FDA approval.

Hospital infections still killing thousands each year

It constantly amazes me when I meet people who want to be hospitalized for something minor. So many patients fail to realize how dangerous the hospital can be. Not only are you at risk for developing a blood clot (deep vein thrombosis or DVT) and dying from it (fatal pulmonary embolism or PE), but you're at very high risk for infection. These hospital-acquired or nosocomial infections are some of the worst types of infections out there!

There's a CNN story about hospital infections and here are the highlights:

• Every year, hospital-acquired infections sicken 1.7 million, kill 99,000 in U.S.
  
• They add more than $28 billion to health care costs annually
  
• Small changes -- using a checklist and brushing patients' teeth -- can lower rates
  
• Expert: Attitude is slowly shifting away from accepting infections as inevitable
  

So, do you enjoy being in the hospital or are you the type who tends to leave against medical advice (AMA)? To read the CNN story, click here.

Are the Days of Coumadin Over?

I know someone on a personal basis (not a patient) who used to take Coumadin for recurrent DVTs. His INR used to go all over the place because he would alter his diet and start new medications that often interacted with Vitamin K. Back in those days, physicians used to dream about a magic pill that didn't require any INR monitoring and that would provide optimal anticoagulation to prevent DVTs. Many people are now wondering, "Is rivaroxaban/BAY 59-7939/Xarelto the first pill that will replace Coumadin and eliminate routine INR monitoring?" I'm very eager to see how other oral factor Xa inhibitors will compare. Is factor Xa inhibition the ideal mechanism? What about factor IIa? Direct thrombin inhibitor? The world of pharmacology is changing so rapidly that it's impossible to keep up with all these changes.