reversing the effects of warfarin and NOACs

It is wonderful that we have such a range of anticoagulation medication available. However, there are times when the effect of that medication needs to be reversed, often quickly. This can happen, for example, in an emergency setting if a patient has a broken leg, is bleeding internally or needs urgent surgery.

There are two main groups of anticoagulants currently in use in Australia: warfarin and the named Non-vitamin K Oral AntiCoagulants) or NOACs.
Warfarin is a drug that works through the vitamin K dependent factors of the coagulation cascade and the NOACs work at precise locations within the coagulation cascade. (Please see page 84.)

When it comes to reversing anticoagulation, the simplest way to achieve it is to withhold the anticoagulation medication. With time, the body produces the factors involved in the coagulation cascade and the system returns to normal. However, for most agents, this will take several days.

In the emergency setting, there is a need to reverse the anticoagulation quickly. This is particularly so in the case of severe haemorrhage when, regardless of the anticoagulant that is being used, fresh frozen blood products are ‘poured’ into the patient.

This literally replenishes the clotting factors that have been blocked by the anticoagulant, quickly returning the coagulation, or clotting, system back to normal.

Some of my patients say they would prefer to stay on warfarin and use vitamin K as an ‘antidote’. They have heard or been told by well-intentioned, but misinformed, parties that vitamin K is the antidote for warfarin. The reality is that the vitamin K-dependent factors take time to produce. So, if a patient on warfarin has bleeding problems and is given vitamin K to overcome the blocking effects in a bid to restore the coagulation system, the liver needs to produce those factors to have the system working again.

It can take six hours or more for the vitamin K-dependent cofactors to start being produced. In the acute, very urgent setting of severe haemorrhage, that process is not fast enough. In that setting, and other urgent scenarios, blood products need to be injected into the person to do the job quickly enough.

In the case of the NOACs, one of the agents, dabigatran, has an antidote that, when injected into the body, binds with dabigatran and makes it inactive. Called idarucizumab, it works almost immediately and is an ideal solution in the setting of uncontrolled bleeding.

Two other NOACs, apixaban and rivaroxaban, have an antidote, andexanet alfa, under development. The trials look promising. If it becomes available, which seems likely, it, too, will be injected into the patient to restore the coagulation system very rapidly.

Access to idarucizumab, and andexanet alfa (if or when it becomes available to clinical practice) means that bleeding patients on a NOAC will not need plasma products ‘poured’ into them if they are having an emergency bleeding problem. Instead, they will simply receive the appropriate antidote to reverse the action of the blood thinner.

Should I swap warfarin for NOACs?

Current guidelines suggest that if an anticoagulant is to be started for a patient with new atrial fibrillation then a NOAC is preferred, understanding that it is not the case if the patient has a mechanical heart valve or mitral stenosis. Similarly, if there are troubles stabilising an INR, warfarin can be swapped to a NOAC.

However, what if the patient is already on warfarin and stable? Patients often wonder if they should or could be on one of the newer anticoagulant agents.

Current wisdom suggests “if it ain’t broke, don’t fix it”, but is there any data to help us?

A paper which pooled the data of more than 40,000 AF patients on either warfarin or a NOAC showed that the rate of stroke was lower in patients taking the NOAC.

In fact, it was nearly 20 percent less and the majority of that difference was driven by a reduction of bleeding into the brain, or haemorrhagic stroke. Surprisingly, this was the case even if the INRs were considered well controlled.

This meant that, overall, the patients taking a NOAC had a lower mortality rate of approximately 10 percent. The NOACs did, however, demonstrate an increase in gastrointestinal bleeds, a somewhat unpalatable problem, but better than bleeding into the brain!

So, what does one do?

While there is no trial looking at this question specifically, nor do current guidelines have a position on changing, my suggestion is to speak with your doctor about the pros and cons for your particular situation.

Having said that, I think if I had AF and was on warfarin, I would be looking to swap to one of the newer agents.

They are easier, with no regular testing needed; they appear safer than and as equally effective as warfarin, and if a NOAC with a single daily dose is chosen, then they are also convenient. Remember, however, there are specific criteria to be met for them to be prescribed and funded in Australia.

Tachycardia Polyuria Syndrome

Interestingly, over the years, I’ve had a number of patients describe very clearly that they need to go to the toilet to pass urine when a rhythm disturbance manifests itself. This is called tachycardia polyuria syndrome or fast heart (tachycardia), leading to an increase in the production of urine (polyuria). Its first documentation was in the 1960s.

Tachycardia polyuria syndrome tends to occur when the patient is in normal, or sinus, rhythm for most of the time but experiences intermittent episodes of the fast arrhythmia. Usually the heart has been beating at more than 100 bpm for at least 20 minutes before the syndrome occurs. More often than not, the palpitation will arise and then 20 to 60 minutes later the need to pass urine follows. This need to pass urine can last for one or two hours, or even up to eight hours, but it depends on how long the rhythm disturbance lasts.

Why does this occur?

We believe that there is a change in pressure in the atria. In atrial fibrillation, as the chamber is not working properly, blood that keeps coming in from the veins and is not pumped out properly can then pool and stretch the atria. This muscle stretch causes a release of special proteins, or messengers, from the atrial tissues into the circulation. These messengers are called atrial (coming from the atrium) natriuretic (producing urine) peptides (mini proteins). So, the stretch on the top chambers of the heart from this arrhythmic disturbance gives rise to the production of messenger peptides which go to the kidneys and tell them to let more fluid go, or release urine.

This syndrome can occur in different types of rhythms within the atria, such as atrial fibrillation or flutter and re-entrant (a short circuit loop) supraventricular tachycardia. It also seems to be different in different people.

It is an interesting scenario and one that I see occasionally. It is not a condition that needs treatment of its own, as treatment of the underlying rhythm will prevent the syndrome occurring.

Do I need a pacemaker?

I am frequently asked by patients with atrial fibrillation if they need a pacemaker. The general answer is “No”.

A pacemaker is a device to provide electrical impetus for the heart when the heart is not producing enough electrical stimulation itself. So, pacemakers are a solution to the heart beating too slowly.

If we think about what is happening in atrial fibrillation, the top part of the heart is beating too quickly, in fact, chaotically. That activity is bombarding the AV node with electrical impulses and those impulses are driving the ventricle to rapid contraction, the ‘irregularly irregular’ heartbeat of atrial fibrillation. So, in general terms, atrial fibrillation does not need a pacemaker because the heart is not going slowly; it is going too fast. Atrial fibrillation generally needs heart rate regulation that slows the heartbeat down, not speeds it up.
    
Occasionally, as is always the case, there are exceptions.

While trying to control the rate of AF, sometimes the medications may not be well tolerated, or they don’t work very well. In these occasional situations, we consider isolating the atria from the ventricles altogether. We do that by AV electrophysiological ablation, a procedure in which we use special catheter techniques to ablate the electrical connection completely, between the top and the bottom of the heart.

This means that the heart, left to its own devices, would generate a heart rate commensurate with what the ventricle would generate by itself, and that is too slow. So, when we do an AV nodal ablation for atrial fibrillation we also insert a pacemaker to ensure that the heart rate is maintained.

There are also situations in which the electrical systems of the heart can be affected by a degenerative process that leads to the failure of the AV node, leading to a ‘heart block’. This condition, just like the deliberate AV nodal ablation, separates the atria and ventricles electrically and will need a pacemaker to maintain an adequate heart rate. This is not linked to the presence of AF and its occurrence represents a second process in the patient, although the frequency of both increases with age.

Do I need a stress test or angiogram?

This is a question that is commonly confronted. It is important as atrial fibrillation and coronary artery disease22 are common companions.

In general terms, if a patient presents in atrial fibrillation with a rapid heart rate, faster than for the expected maximum for that age, then the heart has been put through an auto ‘stress test’23. If at a fast heart rate there are no chest pains and no features on the ECG24 to suggest a lack of blood flow to the heart, then it is likely there are no major blockages in the major arteries.

One confounder is that often when a ‘cardiac patient’ presents at a hospital, a blood test for troponin is performed. This is a really useful test when a patient presents with chest pain.

It returns a positive result when there has been significant strain on the heart. If it rises over time, it could point to possible narrowing of the arteries. If it does not rise, then the heart is less likely to have been the cause of the pain, although it cannot be excluded.

An arrhythmia such as atrial fibrillation can increase the troponin, so how is this dealt with?

My practice is to consider the management based on the presentation:

•    rapid atrial fibrillation, no chest pain, no ECG changes and no
troponin rise

It is hard to make a case for a stress test or an angiogram in this setting, so I treat the atrial fibrillation as appropriate. Later, a more thorough assessment of cardiovascular (CV) disease risk can be made, including absolute risk assessment, plus perhaps the use of imaging. Early use of an invasive angiogram in this setting, ‘just to be sure’, is more than over-cautious; it is probably over-servicing.

•    rapid atrial fibrillation, with chest pain OR suggestive ECG changes OR positive troponin

In this scenario, there may well be an issue with the arteries. The use of risk-modifying drugs becomes important in association with a plan to further evaluate and assess the coronary arteries. My practice is to investigate using an invasive angiogram in highly suggestive situations. I would likely use a stress test or cardiac CT imaging in an intermediate risk patient.

•    rate-controlled or asymptomatic atrial fibrillation

I treat the atrial fibrillation and then work through the process of CV risk assessment.

Can I be screened for AF?

We know a significant percentage of patients have no symptoms and so will be ‘under the radar’. Research is telling us that with one-off rhythm screening in the community of otherwise well individuals over 65 years of age, atrial fibrillation is detected in 1.4 percent. This is about what we would guess from prevalence figures. If we were to provide a hand-held device to 75 year olds for them to check their rhythm twice a day for two weeks, we would likely detect atrial fibrillation at a rate of three percent. These pick-up rates could be increased if we were to screen people who already have increased CHAD scores, meaning the higher-risk population.

At this stage it seems that opportunistic screening, meaning when the individual perhaps sees the local doctor, rather than systematic population based screening is more cost effective. However, the technologies are changing constantly and the goal posts are likely to shift.

There are devices that link to a smart phone and provide a rhythm trace. New smart phone-compatible watches are even being equipped with a rhythm sensing feature.

As amazing as this seems, remember that these personal devices, at least in the early stages, are most likely to be used by younger members of the population who may not be the ones most at risk. Perhaps grandchildren can check out their grandparents?

Also, these devices are likely to over-interpret the presence of atrial fibrillation. As we know not all irregular rhythms are AF, so could these devices ‘over call’ it, thus burdening the health system or creating unnecessary stress for the individual? Time will tell.

Although this is not dedicated screening, the regular interrogation of implanted devices such as pacemakers and loop recorders can demonstrate presence of AF. You might also like to check your pulse occasionally.

Do I need to store AF drugs is a particular way?

Dabigatran should be kept in its original packaging until the time it is taken. Do not put the capsules in a pill box or organiser unless it remains in its foil wrapper. There are no specific storage requirements for warfarin, apixaban and rivaroxaban, beyond keeping them in a cool dry place that is secured and away from children.

How often do I need testing or to see my cardiologist?

The answer to this question will vary depending on your response to treatment although, generally, your cardiologist will see you more often at the beginning of your AF management, and then see you less frequently as the situation becomes more stable.

I see patients a few weeks after an initial diagnosis of atrial fibrillation to ensure that they have remained well and are tolerating the medications. Then I start to stretch out the visits.

If patients are on flecainide, I will see them between six and 12 monthly to repeat an ECG, as the width of the QRS complex can be a clue to the toxicity of the drug.

If they are on digoxin, I like patients to have their levels checked every six to 12 months. It is also important to check renal function. Worsening renal function can lead to digoxin and the NOACs being retained within the body, causing toxicity.

When checking a digoxin level it is generally required to be a ‘trough’ level, that is at its lowest level in the bloodstream, so the test should be taken just before the morning dose. I recommend that digoxin be taken in the morning so that the highest serum levels have the most effect on the patient during the activities of the day. Patients should hold their digoxin dose on the morning of the test and take it straight after the blood has been taken.

Remember, if the level starts to creep up, it may cause nausea and anorexia, so be aware of your last digoxin level if you go off your food.