What You Need to Know about Anticoagulant Therapy

Gregory Piazza, MD

  • Division of Cardiovascular Medicine, Brigham and Women’s Hospital
  • Assistant Professor of Medicine, Harvard Medical School

Anticoagulants or blood thinners are used to treat patients with a number of cardiovascular diseases. Most commonly, we use blood thinners or anticoagulants to treat atrial fibrillation, which is an irregular heart rhythm. We also use them to treat patients who have mechanical heart valves. And then we use them to treat patients who've experienced blood clots in either the veins or the arteries.

There are a number of anticoagulants that are used. We're actually in a very special time in medicine. Over the last five years, we've actually had an explosion in the number of anticoagulant options. For decades we were really limited to warfarin or coumadin, but there have been studies on non-warfarin type anticoagulants that have shown them to be very effective and very safe and those have arrived on the market.

The way that we choose patients for these anticoagulants is to consider what the condition is that the patient has. For things like stroke prevention and atrial fibrillation, we consider both warfarin along with these newer anticoagulants. For patients who have mechanical heart valves or who have valvular disease and are at risk for stroke due to atrial fibrillation, we'll tend to use warfarin more frequently. For patients with blood clots in the veins, such as deep vein thrombosis or pulmonary embolism, we'll use either warfarin or one of these newer agents.

Blood thinners like warfarin and these newer agents, which include dabigatran, rivaroxaban, apixaban, and edoxaban, are all taken by mouth.

Now some of them are taken once daily, some are taken twice daily, and that's something we have to consider when we think of adherence to the medication regimen in our patients. We may opt for a once daily medication to make things a little bit easier, but there also reasons to pick twice daily. So we take into account patient preference and what we think will do the best job.

There are some blood thinners that are given by injection in special circumstances. We don't use those as routinely for stroke prevention and atrial fibrillation, for patients who are at home with mechanical heart valves, and for patients with blood clots who have transitioned from the hospital to home.

Medication Adherence and Anticoagulation Therapy

Medication adherence is a critical issue when it comes to anticoagulation or blood thinning. We know that in patients who miss doses, they're at increased risk for developing blood clotting complications. For patients who may take too much of the medication, misunderstand directions or be given directions that are unclear, if they take more anticoagulant than they're supposed to, they're at increased risk for bleeding. So it's very important to follow the prescription as clearly as possible and to discuss with your clinician exactly how to take these medications.

Laboratory Monitoring of Anticoagulation

INR stands for the International Normalized Ratio. This is a test that was designed so that labs all over the world could have a standardized way of measuring the effect of warfarin anti-coagulation.

For patients taking warfarin or coumadin, measurement of the International Normalized Ratio is routine. The frequency with which that needs to be tested varies depending on how far along in the patient's history they've been taking warfarin. Patients who first start taking warfarin may need pretty frequent INR checks, perhaps once a week, sometimes a little more frequent, sometimes less frequent. Once their INR gets regulated, they may find that they only need to be tested once a month. For the subset of patients who have really great control with warfarin, there are studies that show that they only need to have their INR checked once every quarter.

For the non-warfarin type oral blood thinners, these new ones that have arrived on the market, rivaroxaban, apixaban, edoxaban, and dabigatran, there's no routine monitoring required, because the studies have shown that all patients seem to achieve the same level of anticoagulation and there isn't this variability in dose response that we see with warfarin. So that is another way that these drugs are a little more convenient for patients.

The level of INR varies by the condition being treated. For some mechanical heart valves, we may opt for an INR level or INR range that's higher than we might normally select. But, in general, we look for an INR range from two to three for patients who require anticoagulation for stroke prevention and atrial fibrillation and for patients who have history of a venous or arterial blood clot.

Unfortunately, when patients drop below two, their blood isn't thin enough, and they're at increased risk for developing blood clots. We know that when the INR reaches three and higher, we start to see an increased risk of bleeding. So that's why it's really important to keep the INR between two and three, and that's why we need support from anticoagulation management clinics to really help patients hit that goal.

Side Effects of Anticoagulant Therapy

One of the major side effects of anticoagulation is bleeding. When it comes to warfarin or coumadin, we know that every year that a patient's on that medication, there's somewhere between a one and two percent risk of bleeding.

When you consider the patients who are taking warfarin or coumadin for quite some time, years, sometimes decades, sometimes indefinitely, the risk of bleeding can build up, and that's why we have anticoagulation management services, such as the one that we have here Brigham and Women's Hospital, to help patients monitor their coumadin and change their dose as necessary to avoid higher levels of coumadin than are necessary.

We're very fortunate to have these newer oral anticoagulants, things like rivaroxaban, apixaban, and edoxaban, and dabigatran, because in studies of those drugs compared with warfarin, they seem to reduce the risk of bleeding, in particular, the type of bleeding that we worry about the most, which is intracranial hemorrhage or bleeding on the brain. Using those drugs, in a set of patients that are carefully chosen, may actually improve the safety of anticoagulation and maintain efficacy. That's changed the field and improved patient care.

Drug and Food Interactions Associated with Anticoagulant Therapy

Being on anticoagulation or blood thinners does have implications for a patient's lifestyle. They're critical for treating the underlying medical problem, but they do require patients to make some changes. Patients who are on warfarin may notice that their levels of anticoagulation can change when they eat vitamin K rich foods, such as green leafy vegetables. Their levels may change with increases in alcohol consumption and levels can go up or down depending on the use of certain drugs.

Anticoagulants can interact with other medications. We know from decades of use of warfarin that there are any number of medications that can either increase the effect of warfarin or decrease the effect of warfarin, and can change the International Normalized Ratio. For the newer blood thinners, these non-warfarin type oral anticoagulants, there are much fewer drug-drug and drug-food interactions. For that reason, they're a lot easier for patients to use.

In the case of coumadin or warfarin, the drug interacts with the way that we process vitamin K with regards to our coagulation system. That's why patients who are on warfarin or coumadin may find that their level of anticoagulation, which we call the INR, or International Normalized Ratio, can fluctuate if they eat foods that are rich in vitamin K.

My best advice for patients on anticoagulation with warfarin, is to just make sure that they have the same amount of foods and drinks that may impact their International Normalized Ratio every day. If you're used to having broccoli or spinach in a certain number of servings, you want to maintain those number of servings each day.

Activity Restrictions and Anticoagulant Therapy

With all anticoagulants patients have to be mindful about situations that might increase their risk for bleeding. This is where, unfortunately, we sometimes need to have difficult conversations in the clinic. Patients who are on anticoagulation are at increased risk for bleeding after major trauma.

The important thing that patients also need to understand about anticoagulation is that anticoagulation does not mean that they should avoid all physical activity. Cardiovascular activity like running, biking with a helmet, stationary biking, elliptical use, all of those things are important to maintain good heart health, which actually prevents blood clots and works together with the blood thinner to keep them healthy and they shouldn't give up those important activities just because they're on a blood thinner. They just need to know which activities require more care.

You could imagine that patients who play ice hockey, or practice mixed martial arts, or like to mountain bike or ski, might have to alter their recreational activities in order to maintain safety. What I usually tell my patients is that if they like to ski, they can consider cross country skiing which is safe but downhill skiing is really a problem. A lot of my patients are great skiers and I'm less worried about them and more worried about someone else on the ski slope who may not be experienced and may barrel into them. And if they hit a tree, I've had some patients have either major concussions or intracranial hemorrhage.

When we think of lifestyle, we also have to consider patients' employment. Patients on blood thinners who have occupations that may put them every day at increased risk of trauma, such as police officers, firefighters, construction workers who have to be on high scaffolding, we’ll have to tailor their activities and often have them take some reduced duties that are lower risk while they're on a blood thinner.

Discontinuing Anticoagulant Therapy before Surgery

Interruption of anticoagulation for surgery or other invasive procedures is a common referral question for those of us that take care of patients with these disorders at Brigham and Women's Hospital. We like to see patients so that we can safely determine the way to stop anticoagulation with either warfarin or one of these non-warfarin type anticoagulants and then to help them restart the anticoagulant when it's safe.

For warfarin, in general, we hold four to five doses of the warfarin before a patient goes for an invasive procedure. They would restart the warfarin at their usual dose when their surgeon or the person doing the procedure felt they were safe to do so.

For these non-warfarin type anticoagulants, stopping of the agent varies by the drug and it depends on whether the drug is dosed once daily or twice daily. A lot of the surgeons are just now starting to gain experience with these new drugs so we have to work even more closely with them to help them understand when it’s safe to take a patient to the operating room and when it’s safe to restart anticoagulation.

Benefits and Risks of Novel Oral Anticoagulants (NOACS)

Non-warfarin type oral anticoagulants, which we sometimes call NOACS, are special because they have some advantages when compared with warfarin. But they also have some limitations that we need to keep in mind.

The advantage over warfarin is that these non-vitamin K or non-warfarin type oral anticoagulants (NOACS) have the same dose for most patients. There's not this need, like with warfarin, to take 5 milligrams today, 7.5 milligrams tomorrow. It's the same dose every day for the vast majority of patients.

Another nice thing about these newer drugs is they reach activity very quickly. When you take warfarin, you can expect that your INR won't reach goal for at least five or six days. But with these newer blood thinners, they reach their point of action very quickly. And so within hours of taking a dose, the blood’s thinned. That has some important implications. That means we can give patients these medications, sometimes without needing to do injection therapy to bridge, they can just take these medications and their blood will be anticoagulated. Whereas with warfarin, sometimes we have to give injectable anticoagulation or IV anticoagulation until they get to that INR of two to three. It also means when we have to stop these drugs for procedures, we only have to hold a couple of doses, because the drugs are fast on and fast off.

These newer non-warfarin type anticoagulants don't have as many drug-drug, and drug-food interactions, so we find that they're easier for patients to take. The other nice thing is they don't require regular laboratory monitoring.

However, these drugs, as great as they are, do have some limitations. They are short-acting, which I just mentioned was a bonus for them, but it also can be a problem.

Patients who are prone to forgetting doses or have trouble with adherence to the medication regimen, when they miss a dose, they're actually unprotected very quickly. So if you take something like rivaroxaban once daily with your evening meal, if you miss that dose at your evening meal and fall asleep, you're unprotected as soon as you miss that dose. It's not like warfarin, where the drug tends to hang around for several days. Some patients who miss doses of warfarin may actually notice that their INR still stays within range, because it tends to stay built up in the system, and it takes days to wear off, so that's a limitation.

Warfarin can be reversed a little bit more easily if patients have a bleeding complication or if they overdose. These newer blood thinners do not currently have a specific antidote. We can use some of the therapies that we employ to reverse warfarin with these new drugs, but there aren't great studies to show their efficacy. Luckily, there are some reversal agents that are on the horizon that should be available within the next year or so.

Anticoagulation Management Service at Brigham and Women’s Hospital

At Brigham and Women's Hospital, we pride ourselves on being able to take care of patients who are at risk for blood clotting disorders and who are on anticoagulation. We've been very fortunate to have a long track record of taking care of the most complicated patients with blood clotting diseases who require anticoagulation. We also do a lot of the groundbreaking research that's necessary to improve care in patients who require blood thinners.

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