1. Anticoagulation: The Latest on Blood Thinners from Aspirin to Xarelto
Gail Pokorney, MD
Dine & Discuss
Central Peninsula Hospital
August 20, 2015

2. Objectives Understand why blood thinners are used
Atrial fibrillation
Venous thromboembolism
Mechanical heart valve
Understand the pros and cons of different blood thinners
Warfarin
New Oral Anticoagulants (NOACs)
Objectives

3. Polling the audience How many of you know someone…
Who is on a blood thinner?
Who has atrial fibrillation?
Who has had a blood clot in the leg or the lung?
Who goes regularly to an INR clinic to get a blood test?
How many of you have seen TV advertisements for the new blood thinners?
How many of you have seen lawsuit announcements about the new blood thinners?
Polling the audience

4. A prescription medication that makes your blood less likely to clot
“Anticoagulant”
Anticoagulants prevent clots from forming and treat clots that have already formed
What is a blood thinner?
Anticoagulants do not dissolve clots that exist but prevent clots from growing in size and traveling to a new part of the body.

5. Atrial fibrillation (“A-fib”) = irregular heart rhythm that increases the risk of stroke from a blood clot in the brain
3 million people in the U.S. are affected
Atrial flutter (“A-flutter”) = regular or irregular heart rhythm that has the same risks as A-fib and is managed the same way
Why use a blood thinner?

6. Atrial fibrillation
Lead-in to next slide: So does everyone with this problem need a blood thinner?

7. Age and other medical problems determine the risk of stroke and therefore the need for a blood thinner
Most cases merit anticoagulation
Anticoagulation should continue so long as the A-fib persists
Atrial fibrillation
So does everyone with A-fib need to worry about a stroke and need to be on blood thinners?

8. Venous thromboembolism (VTE) = blood clots in the legs (“deep vein thrombosis” or “DVT”) and lungs (“pulmonary embolism” or “PE”)
1-2 people out of every 1000 are affected
Can form from immobility after surgery
Can form without a trigger
Why use a blood thinner?

9. VTE

10. All people with DVT or PE need to be on a blood thinner for at least 3 months
Sometimes the decision is made to continue anticoagulation indefinitely
VTE

11. Mechanical heart valve = a device used to replace a damaged heart valve
Why use a blood thinner?

12. Mechanical Heart Valve

13. Mechanical Heart Valve
All people with a mechanical valve need to be on a blood thinner indefinitely to prevent a blood clot from forming on the artificial valve
Mechanical Heart Valve
Transition: so now that we’ve talked about the reasons for using a blood thinner, let’s turn our attention to the blood thinner themselves.

14. Blood Thinners: Pros and Cons
All blood thinners prevent and treat clotting
All blood thinners increase the risk of bleeding
Our greatest fear is bleeding in the brain
Bleeding in the stomach/intestines is a major concern as well
Any decision about anticoagulation needs to weigh the benefits of clot prevention against the risk of bleeding
Blood Thinners: Pros and Cons
Refer back to NOAC lawsuit commercials

15. Blood Thinner Options Warfarin (Coumadin) New Oral Anticoagulants
Dabigatran (Pradaxa)
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
Enoxaparin (Lovenox)
Aspirin
Blood Thinner Options

16. Clotting Cascade Warfarin Warfarin NOACs clot + + + + + + X X12
Clotting Cascade
Warfarin X
12a + 11
11a + 9 K 7 K 9a + 10 8a K X
NOACs 7a + 10
10a + 2 5a K
Clotting cascade:
The penultimate step in the formation of fibrin is the conversion of prothrombin (factor II) to thrombin (factor IIa) by the enzyme activated factor X and the cofactor activated factor V. The enzyme thrombin then converts fibrinogen to fibrin in the final step of clot formation.
Warfarin is a vitamin K antagonist. It acts as an anticoagulant by reducing the function of the vitamin K–dependent clotting proteins—factors II, VII, IX, and X—thereby attenuating the extrinsic, intrinsic, and common pathways of blood coagulation. Because of its indirect mechanism of action, the onset and offset of action with warfarin take several days.
In contrast, the NOACs inhibit only a single target—either factor Xa or thrombin – and so have a rapid onset of action.
Peak plasma levels are achieved 1 to 4 hours after oral administration. With half-lives of about 12 hours, the NOACs also have a rapid offset of action. 2a + 1
clot

17. The goal of warfarin is to decrease the clotting tendency of the blood but not prevent clotting completely
The most commonly used test to measure the effect of warfarin is the prothrombin time (PT)
INR is the standardized way to express PT
The longer it takes the blood to clot, the higher the PT and INR
Normal INR is 1
Target INR on warfarin is 2-3
If the INR is below the target range (“under- anticoagulated”), there is a risk of clotting
If the INR is above the target range (“over- anticoagulated”), there is an increased risk of bleeding
Warfarin Monitoring
The most commonly used test to measure the effect of warfarin is the prothrombin time (called pro time, or PT). The PT is a laboratory test that measures the time it takes for the clotting mechanism to progress. It is particularly sensitive to the clotting factors affected by warfarin. The PT is also used to compute a value known as the INR (or International Normalized Ratio).
The INR is a way of expressing the PT in a standardized way; this ensures that results obtained by different laboratories can be reliably compared.
The target INR range depends upon the clinical situation. In most cases the target INR range will be 2 to 3, although other ranges may be chosen if there are special circumstances.

18. Warfarin: What’s Good It works! Inexpensive Familiar
Effective at preventing stroke from A-fib and mechanical valves
Effective at preventing recurrent blood clots in the legs and lungs
Inexpensive
Familiar
We know if you’re taking your medicine
Anticoagulant effect can be reversed with vit K
Warfarin: What’s Good

19. Warfarin: What’s Bad Slow onset of action Dietary restrictions
Interference from other medications
INR results are variable
Requires regular blood tests (“INR checks”)
Antidote does not always work
Bleeding is a major problem
Warfarin: What’s Bad
Many clinical trials find that INRs are in range only 55-65% of the time – and this under the controlled circumstances of a clinical trial.
Risk of major bleeding in patients anticoagulated with warfarin ranges from 0.4% – 7.2% per year
65,000 patients treated annually in US emergency departments for warfarin-related hemorrhage

20. NOACs: What’s Good As good as warfarin at preventing stroke in A-fib
As good as warfarin at preventing recurrent blood clots in the legs and lungs
Start working right away
Wear off quickly
Fixed dose given once or twice daily
No monitoring
Minimal food and drug interactions
Less major bleeding relative to warfarin
NOACs: What’s Good
NOACs were developed to work as well as warfarin and to address the shortcomings of warfarin.

21. NOACs: What’s Bad We can’t tell if you’re taking your medicine
Missing a dose is a big deal
Expensive
No antidote
Still a bleeding risk
NOACs: What’s Bad

22. Some of the differences between the NOACs and warfarin are a matter of convenience, and some can be more serious
Warfarin vs NOACs

23. More about bleeding Not all bleeding is created equal
Intracranial hemorrhage is catastrophic
Nosebleeds, bloody urine, and even GI tract bleeding are all treatable
More about bleeding
3% rate of death or disability for bleeding outside the brain on warfarin vs 76% for bleeding inside the brain

24. Warfarin has an antidote in theory, but in practice it is often too little, too late
It is better to avoid major bleeding in the first place
More about bleeding
Current strategies for reversing the effects of warfarin do not improve outcomes in patients with severe bleeding.
Case-fatality rate after warfarin-associated major bleeding: 13.4%
This is with vitamin K and FFP readily available!

25. NOACs reduce the risk of major bleeding relative to warfarin when used to treat DVT and PE
NOACs reduce the risk of death and intracranial bleeding relative to warfarin when used to treat A- fib
Apixaban reduces the risk of GI bleeding as well
Remember: risk of bleeding with warfarin is closely linked to the consistency of the INR
More about bleeding
Major bleeding = fatal bleeding, bleeding in a critical area or organ, or bleeding causing a fall in hemoglobin of 2 mg/dL.

26. To switch or not to switch?
Consider a switch
Variable INRs
Burdensome monitoring (“warfarin hate factor”)
High risk of bleeding
Do not switch
Consistent INRs
Cost/coverage issues
Difficulty remembering to take medications
To switch or not to switch?

27. Who should not use a NOAC?
Mechanical heart valve
Abnormal kidney or liver function
Blood clot in the setting of active cancer
History of gastric bypass surgery
Weight extremes
Pregnancy
Who should not use a NOAC?

28. Tips for blood thinner use
Know your dose
Know why your doctor is prescribing it for you
Take it exactly as prescribed; never miss a dose
Do not use NSAID pain relievers, like ibuprofen or naproxen
Ask your doctor before taking any new medications, including OTCs and supplements
Tips for blood thinner use

29. What about those injections?
Enoxaparin (Lovenox) is a blood thinner used in the following circumstances:
Bridge to warfarin
Bridge to dabigatran and edoxaban in the treatment of DVT and PE
Primary treatment of DVT and PE in the setting of active cancer
What about those injections?

30. Aspirin works differently from all the other blood thinners discussed in this talk
Aspirin interferes with the function of platelets, which are small blood cells involved in the clotting process
Aspirin is used in a wide variety of medical conditions, not just the ones discussed in this talk
Ex: coronary artery disease
What about Aspirin?

31. Aspirin is no longer recommended for stroke prevention in A-fib
In people taking both aspirin AND warfarin or a NOAC, aspirin may increase the risk of bleeding without providing additional protection against clots
Bottom Line: if you are taking aspirin for stable heart disease, as well as warfarin or a NOAC for A- fib, ask your doctor if you need to stay on aspirin
What about Aspirin?

32. Summary of key points All blood thinners prevent and treat clotting
All blood thinners increase the risk of bleeding
Any decision about anticoagulation needs to weigh the benefits of clot prevention against the risk of bleeding
Individualized decision
Some of the differences between warfarin and the NOACs are a matter of convenience, and some are more serious
Refer to your hand-out for a summary
Summary of key points

33. Case #1 50-year-old man with a new diagnosis of PE
No other medical problems
Travels frequently for business
Case #1

34. Case #2 80-year-old woman presenting to the ER with a stroke
Heart monitor in the hospital shows atrial fibrillation
Also has severe chronic kidney disease
Case #2

35. Questions?