Category Archives: Blood Thinners/Anticoagulants

What Can You Really Learn From Celebrity Bob Harper’s Heart Attack And Near Sudden Death?

Until recently I had never heard of Bob Harper (The Biggest Loser) but apparently he is a celebrity personal trainer and had a heart attack and nearly died.  He  is known “for his contagious energy, ruthless training tactics, and ability to transform contestants’ bodies on The Biggest Loser” (a show I’ve never seen.)

When celebrities die suddenly (see Garry Sanders, Carrie Fischer) or have a heart attack at a youngish age despite an apparent healthy lifestyle this get’s people’s attention.

The media typically pounce on the story which combines the seductive allure of both health and celebrity reporting.

It turns out Harper inherited a high Lipoprotein (a) (see here) which put him at high risk for coronary atherosclerosis (CAD) which ultimately caused the heart attack (MI)  that caused his cardiac arrest.

To his credit, Harper has talked about Lipoprotein (a) and made the public and physicians more aware of this risk factor which does not show up in standard cholesterol testing.

Since his heart attack, Mr. Harper of “The Biggest Loser” has embarked on a newfound mission to raise awareness about heart disease and to urge people to get tested for lp(a).

Harper As Brilinta Shill

Unfortunately , he has also become a shill for Brilinta, an expensive brand name anti platelet drug often prescribed in patients after heart attacks or stents.

At the end of the TV commercial he says “If you’ve had a heart attack ask your doctor if Brilinta is right for you. My heart is worth Brilinta.”

At least this video is clearly an advertisement but patients and physicians are inundated  by infomercials for expensive, profit-driving drugs like Brilinta.

This Healthline article pretends to be a legitimate piece of journalism but is a stealth ad for Brilinta combined with lots of real ads for Brilinta.

Harper As Lifestyle Coach.

Harper also changed his fitness and diet regimens after his MI reasoning that something must have been wrong with his lifestyle and it needed modification.  For the most part he talks about more “balance” in his life which is good advice for everyone. His fitness regimens pre-MI were incredibly intense and have been toned down subsequently.

After his heart attack, Bob abandoned the Paleo lifestyle for the Mediterranean diet, as it’s been proven to improve heart health and reduce the risk of a heart attack, stroke, and heart-disease-related death by about 30 percent. But recently, he’s moved closer to a vegetarian regimen.

Of course, vegans and vegetarians have seized on this change in his diet as somehow proving the superiority of their chosen diets as in this vegan propaganda video:

Unfortunately there is no evidence that changing to a vegan or vegetarian diet will lower his risk of repeat MI.  Those who promote the Esselstyn, Pritikin or Ornish type diets claim to “reverse heart disease” and to be science-based but, as I’ve pointed  out (see here) the science behind these studies is really bad.

In fact, we know that neither diet nor exercise influence lipoprotein(a) levels which Bob inherited.  Some individuals just inherit the risk and must learn to deal with the cardiovascular cards they’ve been dealt.

What Can We Really Learn From Bob Harper’s Experience?

  1. Lipoprotein (a) is a significant risk marker for early CAD/MI/sudden cardiac death. Consider having it measured if you have a a) strong family history of premature deaths/heart attack (b) if you have developed premature subclinical atherosclerosis (see here) or clinical atherosclerosis (heart attack, stroke, peripheral vascular disease) or (c) a family member has been diagnosed with it.
  2. Everyone should learn how to do CPR and how to utilize an AED. (see here for my rant on these two incredibly important 3-letter words). Harper was working out in the gym when he collapsed. Fortunately a nearby medical student had the wherewithal to do CPR on him until he could be defibrillated back to a normal rhythm and transported to a hospital to stop his MI.
  3. Dropping dead suddenly is often the first indicator that you have advanced CAD. If you have a strong family history of sudden death or early CAD consider getting a coronary artery calcium scan to better assess your risk.

Focus on celebrities with heart disease helps bring awareness to the public about important issues but we can only learn so much about best lifestyle or medications from the experience of one individual, no matter how famous.

Brilliantly Yours,

-ACP

Is It Safe To Consume Grapefruit If You Take The Blood Thinner Apixiban (Eliquis)?

A patient of mine with atrial fibrillation taking the blood thinner eliquis told me that she had eaten grapefruit for two days in a row and then developed a nose bleed. She had heard of the interaction between grapefruit and certain medications and wondered if this had caused her nose bleed.

I was unaware of any eliquis/grapefruit interaction but thought this was a remarkably astute observation and question and set about to research it properly.

Among other things, I discovered that some researchers believe the grapefruit-drug interaction to be a widespread , underreported and  highly significant problem while others feel it is overblown and a rare cause of clinically important side effects.

For those, who prefer not to delves into the gory details I give you the crux of what BMS/Pfizer, the makers of apixiban (Eliquis) told me and with which I agree:

When consumed in usual dietary volumes, grapefruit juice is considered a moderate inhibitor of CYP3A4. Therefore a dose adjustment of apixaban is not expected to be required.

In other words, although not formally studied, there is no evidence that apixiban levels are increased by moderate grapefruit juice ingestion to a degree that would cause significant bleeding complications.

Although multiple sites on the internet (including the unreliable Web MD) will tell you of a potentially dangerous interaction between grapefruit and apixiban this theoretical interaction has not proven clinically significant.

Interactively Yours,

-ACP

Below is the full text of the letter BMS sent me

Bristol-Myers Squibb and/or Pfizer have not conducted any studies evaluating the concomitant use of apixaban and grapefruit juice. The decision to prescribe apixaban in patients who are concomitantly taking grapefruit juice is a clinical decision for the treating physician based on the individual’s circumstances and inaccordance with the full prescribing information for apixaban.

While in vitro data indicates grapefruit juice can inhibit both cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), clinical evidence suggests that grapefruit juice mediated interactions would be primarily due to the inhibition of CYP3A4 and the contribution of P-gp inhibition may be limited.1, 2 When consumed in usual dietary volumes, grapefruit juice is considered a moderate inhibitor of CYP3A4.1 Therefore a dose adjustment of apixaban is not expected to be required.

Apixaban is eliminated from the body through multiple pathways, with approximately 25% of the administered dose recovered as metabolites. The main metabolic pathway for apixaban is through CYP3A4/5, with minor contributions from other CYP isoenzymes. Apixaban is also a substrate of transport proteins P-gp and breast cancer resistance protein.3

  1. [1]  Hanley MJ, Cancalon P, Widmer WW,et al. The effect of grapefruit juice on drug disposition. Expert Opin Drug Metab Toxicol. 2011; 7(3):267-286.
  2. [2]  Farkas DG and Greenblatt DJ. Influence of fruit juices on drug disposition: discrepancies between in vitro and clinical studies. Expert Opin Drug Metab Toxicol. 2008;4(4):381-393.
  3. [3]  Eliquis® (apixaban) Package Insert. Bristol-Myers Squibb Company, Princeton, NJ and Pfizer Inc, New York, NY

Blood Thinners (Oral Anticoagulants) For Atrial Fibrillation: Who Should Take Them and Which One To Take

The most serious  adverse consequence of having atrial fibrillation is stroke. Since we have safe and effective ways of preventing afib-related stroke with oral anticoagulant drugs (blood thinners), a major decision for the newly diagnosed patient with atrial fibrillation is “should I take a blood thinner?”

To answer this question the afibber should engage in a lengthy discussion with his/her health-care provider which results in a shared and informed  decision. Such discussion must cover your risk of stroke, the benefits of blood thinners in preventing stroke, the bleeding risks of blood thinners and the pros and cons of the five oral anticoagulants available to prevent stroke.

Estimating Your Risk of Stroke With Afib

The best way we have of estimating a patient’s risk of stroke if they have atrial fibrillation (AF) is by the CHA2DS2-VASc scale (which I like to call the Lip scale)

Stroke Risk EstimationThis scale take the factors we know that increase the risk of stroke and assigns 1 or 2 points. The acronym comes from the first letter of the factors that are known to increase risk as listed to the left.

Most of the factors get 1 point, but prior stroke (S) and age>75 (A) get 2 points.

We then add up your points and use another chart (or app) to calculate the risk of stroke per year.

CHA2 stroke riskYour risk of stroke is very low if you have zero risk factors; it gets progressively higher as you reach the maximum number of 9.

Treatment with an oral anticoagulant (OAC),  either warfarin, or one of the four novel anticoagulant agents (NOACS), is recommended when score is >/=2 corresponding to a  risk of stroke  above 1-2% per year.

These blood thinners have consistently been shown to lower your risk of stroke or systemic embolization (when a clot from the heart goes somewhere other than the brain) by almost 70%.

The higher the risk, the more the benefit of these blood thinners in preventing stroke.

Both European and American guidelines recommend using the CHA2DS2-VASc score for initial risk stratification. The European  guideline recommends OAC therapy for males with a CHA2DS2-VASc score ≥1 and for female patients with a score ≥2., whereas the American guideline recommends use of OAC if the CHA2DS2-VASc  score is ≥2 for men and women.

I’ve been using the CHA2DS2-VASc scale for several years in my afib patients. I try to review the patient’s risk of stroke and their risk of bleeding during every office visit, and decide whether they should be on or off an OAC.

Bleeding From Blood Thinners

All OACs cause increase bleeding. They don’t discriminate between bad clots that cause strokes and good clots that stop you from bleeding.

If you’re taking one you are more likely to have nose bleeds, bleeding into the intesitnal tract or urine and you will bleed longer when cut and more profusely if in an accident. In lower stroke risk patients, the bleeding risk of OAC of 1% per year may outweigh the benefits conferred by stroke reduction.

I wrote a post entitled “Why Does The TV Tell me Xarelto Is a Bad Drug” which points out that law suits against the makers of the newer OACs are frivolous and that these NOACs are likely more safe and effective than warfarin.

In recent years, four new drugs for reducing strokes in patients with atrial fibrillation which are much less influenced by diet and medications have gained approval from the FDA. These are generally referred to as “novel anticoagulants” reflecting their newness, different effects from warfarin or aspirin, and their blood thinning properties.  The first  (brand name Pradaxa) was released to much excitement and fanfare in October, 2010.  The press release for this approval read as follows:

PRADAXA, an oral direct thrombin inhibitor2 that was discovered and developed by Boehringer Ingelheim, is the first new oral anticoagulant approved in the U.S. in more than 50 years. As demonstrated in the RE-LY® trial, PRADAXA 150mg taken twice daily has been shown to significantly reduce stroke and systemic embolism by 35 percent beyond the reduction achieved with warfarin, the current standard of care for patients with non-valvular atrial fibrillation. PRADAXA 150mg taken twice daily significantly reduced both ischemic and hemorrhagic strokes compared to warfarin

What was very clear from the study with Pradaxa  and stated very clearly in all publications and patient and doctor  information sources was that just like warfarin, patients could have severe bleeding complications, sometimes fatal. Overall serious bleeding complications were about the same (the rate of major bleeding in patients Pradaxa  in the RE-LY trial was 3.1% versus 3.4% in the warfarin group) but Pradaxa had about 50% more bleeding from the gastrointestinal tract and warfarin about 50% more bleeding into the brain.

Another big difference between the novel anticoagulants and warfarin is that we have antidotes (Vitamin K, fresh frozen plasma) that can reverse the anticoagulation state rapidly for warfarin but until recently none for the newer drugs. (There is now available an antidote for Pradaxa).  This information also was made very clear to all doctors prescribing the medications in the package insert and educational talks. Despite this, in the major trials comparing these newer agents to warfarin, the newer agents were as safe or safer than warfarin.

The most feared bleeding complication on all OACs is bleeding into the head (intracranial hemorrhage). The risk of ICH is between 0.2 to 0.4 percent per year on warfarin. Studies show with the NOACs the risk is about half of the risk on warfarin.

Should You Take a NOAC or Warfarin?

Once the decision has been made to start a blood thinner, the next question is whether to take warfarin or a NOAC. Warfarin (brand name Coumadin) has been utilized since the 1950s  and prior to 2010 was  the only drug available for doctors to reduce clot formation in the heart and susbsequent strokes.. Warfarin is only effective and safe within a narrow window and its effects are strongly influenced by Vitamin K in the diet and most medications. Thus, frequent blood testing and adjustment in dosage is needed, and close monitoring of diet and changes in medications. Even with this close monitoring, serious and sometimes fatal bleeding occurs frequently with warfarin.

Here is a patient information sheet on warfarin which gives you an idea of issues you will need to be aware of when taking the drug. (WArfar patient handout)

If you do a Google search on warfarin you will quickly discover that it is used as a rat poison. Scientists isolate the chemical from  sweet clover that was causing cows to bleed and then developed a more potent form that they named warfarin in the 1940s. After developing blood tests that allowed the drug to be used safely  to dissolve clots it was approved for human use in the 1950s.

Warfarin or more potent variations on its chemical structure have been utilized as rat poison since the 1940s.

The rats are consuming much larger quantities of the blood thinner and are clearly not being monitored for blood thinness.

Some despicable sites peddling alternative or natural products such as this “Healthy Habits” site engage in fear-mongering over the warfarin/rat poison connection in order to promote totally unproven products. Healthy Habits indirectly suggests  that Nattokinase : is a safer, more effective natural alternative to warfarin” This remarkable enzyme has the ability to dissolve blood harmful clots involved in heart disease and strokes without upsetting normal healthy clotting.”

Such misinformation is dangerous and could lead to patients stopping a life-saving medication and suffering a stroke.

By the way, in this Xarelto (another NOAC competitor) ad, Screen Shot 2016-06-29 at 2.21.20 PMKevin Nealon says he chose Xarelto over warfarin because he wanted to eat salads. This is a common misconception and the makers of Xarelto should be ashamed for promulgating it.

I tell my patients it is fine to eat green, leafy vegetables while taking warfarin. The Vitamin K in the vegetables does influence the effectiveness of warfarin thinning blood but this is why we check the blood test to determine the appropriate dosage of warfarin for you and your personal dietary Vitamin K consumption , be it high or low.

Novel Oral Anticoagulant Drugs

The newer OACs, in contrast to warfarin do not require blood tests for monitoring of their efficacy because their levels are not significantly influenced by changes in diet or most medications.

In head to head studies versus warfarin four of these NOACs have demonstrated at least similar efficacy in preventing stroke and at most similar bleeding risk.

Due to their perceived advantages most new prescriptions for OACs are for NOACs. In contrast to 2014 American afib guidelines which don’t state a preference, the most recent European afib guidelines recommend choosing a NOAC over warfarin when initiating anticoagulant therapy in patients who are eligible for NOACs. (Ineligible patients include those with mitral stenosis, mechanical heart valves and end-stage renal disease.)

The ESC guidelines published in 2016, , make choosing a NOAC over warfarin a IA recommendation. This means there is a consensus that the treatment should be recommended (Class I recommendation) and that there is strong evidence from randomized controlled trials to support it (Level A.)

I have decided to primarily use Eliquis (apixaban) as my NOAC of choice based on my comparison of the different NOAC studies. If a patient’s insurance covers another NOAC better , making it cheaper then  I am happy to switch.

Because these four NOACs are new and brand name they are significantly more expensive than warfarin. Cost varies substantially based on type of insurance coverage and we can only determine how much a patient will pay for any given NOAC based on writing a prescription and having a pharmacy check out the cost.

I have found some patients paying nothing for their NOAC whereas some are paying several hundred dollars monthly. The more NOACs cost, the more likely the patient and I are to choose warfarin.

While waiting to determine if cost is going to be prohibitive I will typically provide the patient with samples of the NOAC chosen. The pharmaceutical companies making these NOACs are clearly making substantial profits off them and they are happy to provide lots of samples to doctors to influence the doctors to utilize their product.

NOACs are being extensively promoted both to physicians and directly to patients. Physicians have to be especially careful to make sure they are presenting a true summary of the relative risks and benefits of warfarin versus NOACs in light of these constant attempts to influence them.

Despite now having four NOACs with similar benefits and ease of use compared to warfarin, the cost of these agents doesn’t seem to have declined significantly from when the first NOAC came on the market. Personally, I would love to see Medicare step in and negotiate significantly lower costs for American senior citizens.

An abstract at the ACC meeting in March of 2017 suggested  a reduction in medical costs with NOACs despite their high costs. This was related to a lower rate of major bleeding complications: Xarelto cost $542 per patient compared with warfarin’s $500, or $42 more. Pradaxa, cost $367 to warfarin’s $452, saving $85.  Eliquis cost  $286 charge against warfarin’s $537 resulting in $251 in savings. Data were from from a study of U.S. Medicare patient records.

Aspirin May Not  Prevent Stroke In Afib

Many patients consider aspirin to be  a “blood thinner” that has some benefit in preventing clots and strokes in patients with afib. However,  aspirin is not considered a blood thinner or anticoagulant and is more properly  termed an anti-platelet agent.

I used to consider aspirin at doses of 120 to 200 mg daily provided some protection against stroke in afib and put afib patients on aspirin who were low risk for stroke or would not or could not take OACs.

More and more, however, experts are reaching the conclusion that the substantial bleeding complications from aspirin usage outweigh its very slight benefit in stroke prevention.

The most recent ESC guidelines, in fact, list aspirin therapy for stroke prevention in atrial fibrillation as IIIA. That means that overall it is felt to be harmful (III) with a high level of evidence (A.)

Bleeding risks for aspirin are similar to warfarin and Eliquis. Thus, patients should not consider aspirin as a safer alternative to prevent stroke in afib.

Finally, do not take any “natural” supplement that has been promoted as a blood thinner. These are neither safe nor effective. Remember that it took years of scientific investigation and careful testing in animals then humans before warfarin (the agent in sweet clover that caused cows to bleed ) was transformed into a safe and effective anticoagulant.

Antiemboligenically yours

-ACP