The 1940s and '50s were a time of great medical
advances in life-saving drugs. And while
wonder drugs like antibiotics were making
waves, another important drug was hitting the
market: warfarin.
Warfarin, which is also known by its brand
name Coumadin, is one of the first and most widely used anticoagulants.
In fact, not long after it was introduced, it was
administered to President Dwight D. Eisenhower for treatment
after a heart attack. Several decades later, it's still being
used successfully to treat patients with atrial fibrillation,
deep vein thrombosis (DVT), pulmonary embolism (PE) and
heart attack. However, newer anticoagulants offer similar or
more effective—and safer—results.
understanding anticoagulants, old and new
For all of its successes, warfarin comes with some inconveniences.
It is a drug that interacts negatively with many
other drugs and with high vitamin K intake in the diet.
"When all we had was warfarin as our oral blood thinning
medication, we had to be very careful about which drugs
we prescribed it with," says Jeffrey Weitz, MD, professor of
medicine, biochemistry and biomedical sciences at McMaster
University in Hamilton, Ontario, and executive director
of the Thrombosis and Atherosclerosis Research Institute,
which is also in Hamilton. "It interacts with just about every
drug you can imagine. And those other drugs can increase
or decrease the anticoagulant effects in warfarin. It is a real problem because it is really hard to keep all of the different drug
interactions straight."
And not only did doctors and patients have to watch other
drugs, they had to keep an eye on supplements and dietary intake
as well. "With warfarin, the vitamin K intake in your diet will
affect the anticoagulant activity of warfarin," continues Dr. Weitz.
"It has to do with how warfarin operates in the body. it works by
interfering with the vitamin K cycle in the liver. If you have a lot
of that vitamin in your diet, you'll need more warfarin."
So, while warfarin served the 20th century well, it's now
the 21st century, and a more advanced breed of blood thinners,
which have been in development for the past several years, are
starting to hit the market.
"These new oral agents are creating a lot of excitement
because, for 60-odd years, all we had was warfarin," says Dr.
Weitz. "Finally, we're seeing the availability of new options that
streamline long-term anticoagulation management."
Dr. Weitz says that the newer types of anticoagulants don't use
the vitamin K mechanism and thus create fewer interactions and
adjustments of dosage. Although, the goal—preventing fibrin
formation—is still the same, the method the new anticoagulants
employ is specific enzyme targeting. Fibrin is the material in the
blood that ties together clumps of platelets to create clots. The
primary job of an anticoagulant is to prevent the formation of
fibrin. (Turn to page 16 to learn more about the roles of different
blood clot medications.)
"There are two key enzymes—thrombin and factor Xa
(pronounced "ten a")—in the clotting mechanism that drive the
formation of fibrin strands," says Dr. Weitz. "The new anticoagulants
target one or the other of those enzymes. So with these
newer agents, the drug interactions are much more limited; doctors
and patients don't have to worry as much about that factor."
Meet the new anticoagulants
There are actually a number of these new drugs, but as of
right now, only one is approved by the U.S. Food and Drug
Administration (FDA). The two you should know about are dabigatran,
which is a thrombin inhibitor, and rivaroxaban, which
targets factor Xa.
Dabigatran, which has the brand name Pradaxa, is licensed in
the United States as an alternative to warfarin for stroke and
blood clot prevention in people who have atrial fibrillation. It
targets the enzyme thrombin. The other new anticoagulant,
rivaroxaban, targets the other fibrin-creating enzyme, factor Xa.
Dr. Weitz explains that thrombin is the enzyme that converts the
soluble protein fibrinogen into insoluble fibrin, while factor Xa
is the enzyme that generates thrombin. Rivaroxaban, which has
the brand name Xarelto, is under consideration by the FDA for
both prevention of DVT after hip or knee replacement surgery
and for stroke prevention in patients with atrial fibrillation.
"These are both oral drugs that will likely replace warfarin
for long-term anticoagulation for the prevention or treatment
of clotting," says Dr. Weitz. "However, there are more to come.
We've only seen the tip of the iceberg where these new drugs
are concerned."
