Eliquis vs Xarelto, Pradaxa, Coumadin, and Aspirin
“Blood thinner” is a misleading term. What is implied is that it dilutes the thickness of the blood, such that very thick accumulations (clots) won’t happen. In reality, blood thinners alter the body’s clotting mechanism at the cellular level. To make a clot, there is a cascade of changes—a falling of dominoes. What blood thinners do is interfere with that cascade—pick up one domino so that the sequential falls are stopped at that blank spot.
It’s not like self-sealing antifreeze
Clotting is the body’s way of self-sealing. Because it is also involved in repair of damaged tissue, initiating of healing, and an integral part of the entire inflammatory process, it is not like Silly Putty or self-sealing antifreeze.
Clotting is tricky: too much and blood won’t flow (as in a blood clot in a vein); too little and blood flows too much, flooding tissues destructively (as in a stroke) or hemorrhaging to death from minor trauma. For this reason, clotting has been an evolutionary challenge. Mammals have risen to the challenge, however, in making a sequence—from beginning to end—with a number of checks and balances. The clotting “cascade,” as it is called, is very complex and all of the steps are needed for successful stopping of blood flow with injury. Additionally, the clotting system overlaps with the immune system to trap organisms.
It all starts with injury and platelets
If tissue is injured enough to bleed, this means blood vessels in that tissue have been damaged enough to begin leaking blood. The internal lining of the blood vessels, exposed to the external world, signal blood cells called platelets to clump together to seal the leak. While one may be tempted to say, “Aha! It really is like self-sealing antifreeze,” what follows is anything but a plug. The initial platelet response is called primary hemostasis. (“Hemo” = blood; “stasis” = stop.) It is the finger in the dike until the right material can be applied for a permanent fix. Besides clumping together, the activated platelets in primary hemostasis also release their contents into the bloodstream to call more platelets to the site.
What follows is the secondary hemostasis, the final seal important in healing.
It all ends with fibrin
Vigilant coagulation factors are proteins and enzymes, generally, and are inactive unless something calls them to activate. The initial primary hemostasis is just such a provocation. Numerous coagulation factors begin to engage the activation of circulating inactive factors, and after a complicated multiple-pathway string of biochemical reactions, prothrombin begets thrombin, which amplifies the whole process to finally result in fibrin strands that are laid down into what will become a scab externally or a clot (thrombus) internally.
Of all the factors, all of them important, the most significant is thrombin, which amplifies the whole process as well as promotes the “stickiness” of platelets.
Apples and Oranges
Which dominoes in the clotting cascade are removed, of course, is the strategy by which each blood thinner medication works. The dominoes are different, as different items in the clotting cascade are altered toward clotting interference. The most popular blood thinners, regardless of mechanism, are
- Warfarin (Coumadin). This is the old standby and along with aspirin, is the cheapest. It interferes with the role of Vitamin K, which is needed to activate many of the clotting factors. It can be taken once daily, but the clotting modulation needs to be monitored closely, to make sure this medicine doesn’t overshoot and result in dangerous bleeding. It is followed with a measurement representative of the clotting processes called an INR, done at least monthly. The routine blood work is a drag and the biggest reason for patients wanting to change to the newer “blood thinners,” below. Another drawback for it is that the amount of Vitamin K consumed in vegetables, for instance, must be monitored closely, too. Eating a lot of Vitamin K will defeat the whole purpose of being on something that is designed to oppose it.
Because warfarin may be working fine, ditching it may violate the rule that says, “If it ain’t broke, don’t fix it.”
Warfarin will not dissolve a clot already in place. In fact, the others (below) are considered preventative when there has been shown to be a clot already or if there is a medical or surgical condition that would make a patient prone to flipping blood clots through the body, such as atrial fib. To dissolve clots already there, medications called thrombolytics are used, but this is such a tricky maneuver that the benefit (saving life) must far outweigh the risk (ending life!).1
The newer blood thinners eliminate the persnickety need for routine blood testing and dietary concerns:2
- Apixaban (Eliquis). This inhibits a clotting factor called Factor X, not to be confused with Simon Cowell’s X-factor. (The factors are labeled as Roman numerals.) Apixaban actually inhibits the “activated” Factor X, called “Factor Xa.” It also inhibits the ability of platelets to stick together, the conversion of prothrombin to throbin (the clotting sequence amplifier), and finally the last phase of clotting—fibrin clot formation.
- Dabigatran (Pradaxa) works similarly to Eliquis (above). It is actually a “prodrug,” something that gets converted into the actually working medication, which is dabigatran. This extra step in delivery extends its time in the body, but like Eliquis, is given twice a day.
- Edoxaban (Savaysa) is also a Factor Xa inhibitor. It inhibits thrombin-induced platelet aggregation by reducing the generation of thrombin from prothrombin.
- Rivaroxaban (Xarelto) is a Factor Xa inhibitor; it also inhibits platelet activation by interfering with the conversion of prothrombin to thrombin.
To summarize, the older blood thinner, warfarin (Coumadin), opposes Vitamin K which is important in activating the other clotting factors. The newer ones hone in on a clotting factor, usually Xa, to thwart the conversion of prothrombin to thrombin and decrease the effectiveness of platelets to stick together.
How does one choose which blood thinner?
What’s best for one may be worst for another. Choosing the right one may be based on:
- Finances (some insurers won’t cover blood thinners more expensive than warfarin).
- Convenience: the inconvenience of routine blood tests or keeping tab of Vitamin K intake may be enough of a deal breaker to make someone want to choose a medication other than warfarin.
- Another convenience factor is the dosage:3
- Eliquis and Pradaxa are taken twice a day.
- Warfarin, Xarelto, and Savaysa are taken just once a day.
- Safety. Warfarin is the oldest so in spite of the frequent testing necessary, has the longest track record. It is also safest with kidney failure or heart valve disease.
- Efficacy. The body changes but the medicines stay the same. This means that one medication may work great now, but six months from now may need to be changed. Alternately, one that doesn’t work well now may be the perfect choice six months from now.
Which is best?
There are no studies comparing the blood thinners head-to-head.4 None completed yet, anyway. In an ongoing study called “Aristotle,”5 Eliquis was leading in efficacy and safety over the others, but the advantage may yet be determined to be insignificant and the comparisons to warfarin may have conflicting measuring methods. Other studies are ongoing as well. Until there’s a conclusion of one clearly superior over the other, choice must depend on the financial, convenience, safety, and efficacy concerns.
- Konstantinides SV, Vicaut E, Danays T, et al. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol 2017; 69:1536.
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