Tag Archives: Pradaxa

Are Physicians Influenced By Pharmaceutical Gifts?

The Skeptical Cardiologist stopped giving talks for pharmaceutical companies 5 years ago and stopped accepting lunches from pharmaceutical reps because he wanted to be certain that he was not being influenced by them in his writing or patient care.

I made an exception 6 months ago and consumed panang curry provided by a pharmaceutical representative who was promoting the blood thinner Pradaxa.

He enthusiastically extolled the virtues of Pradaxa throughout the lunch and made some excellent points supporting the use of the drug. Shortly thereafter, when I was considering which of the newer blood thinners to prescribe for a patient , Pradaxa was foremost in my mind.

The scientific data that Boehringer Ingelheim wanted me to be aware of entered the crowded marketplace of ideas in my head that day but I prefer the data that enters my consciousness come from unbiased sources.

A new study from Georgetown University, published in PLOS One provides support for physicians eschewing pharmaceutical gifts.

The authors point out in their introduction that gifts are important:

Gifts, no matter their size, have a powerful effect on human relationships. Reciprocity is a strong guiding principle of human interaction. Even gifts of small value, such as “modest” industry-sponsored lunches, may foster a subconscious obligation to reciprocate through changes in prescribing practices. DeJong et al has shown that a meal with a value of less than $20 can increase the prescribing of branded statins, beta-blockers, ACE inhibitors, and antidepressants.

The study found:

Physicians who received small gifts (less than $500 annually) had more expensive claims ($114 vs. $85) and more branded claims (30.3% vs. 25.7%) than physicians who received no gifts. Those receiving large gifts (greater than $500 annually) had the highest average costs per claim ($189) and branded claims (39.9%) than other groups. All differences were statistically significant (p<0.05).

The conclusions of the study:

Gifts from pharmaceutical companies are associated with more prescriptions per patient, more costly prescriptions, and a higher proportion of branded prescriptions with variation across specialties. Gifts of any size had an effect and larger gifts elicited a larger impact on prescribing behaviors. Our study confirms and expands on previous work showing that industry gifts are associated with more expensive prescriptions and more branded prescriptions. Industry gifts influence prescribing behavior, may have adverse public health implications, and should be banned

Michael Joyce has written a detailed and insightful analysis of this paper at the excellent website, HealthNewsReview.org.

He points out the limitations of this and all observational studies:

Although the study cannot definitively establish cause-and-effect between a provider receiving such gifts and any subsequent upturn in their prescribing, it does make a significant contribution to a growing body of literature documenting how drug company largesse is clearly linked — either consciously or otherwise — to the way in which health care providers prescribe.

And the article quotes Daniel Goldberg, an expert on bioethics:

“First, in situations when the evidence is imperfect, and the decisions are subtle, as is so often true in medicine. In these ambiguous situations the evidence clearly suggests that gifts can sway doctors in one direction, even if there’s no evidence to support that as the best decision. Second, it frames decisions in pharmaceutical terms, even when there may be other options — proven to be better — that have nothing to do with drugs.

Drugs are just one tool. But we have ‘pharmaceuticalized’ health care to a point where many patients are conditioned to equate health with access to drugs.”

Since I consumed the panang curry, I’ve gone back to bringing in my own lunch. Thus, my lunch/breakfast typically consists of Trader’s Point full fat plain yogurt with lots of blueberries and raspberries, and perhaps some ground up flaxseed and/or almonds (although today I’ll be bringing in leftover-meatloaf and roasted root vegetables.)

It’s not as tantalizing as the curry, but it leaves my crowded brain free to ponder the multitude of unbiased data from scientific papers, rather than the talking points a pharmaceutical representative would prefer I ponder.

The end result, I hope, is unbiased blogging and prescribing-better information for readers and better care for patients.

-ACP

 

Why Does The TV Tell Me Xarelto is a BAD DRUG?

One of my patients called the office today concerned about a medication she was taking because she was “seeing about 4-5 commercials a day about how bad Xarelto is”.

She is the latest of many of my patients who have been inundated with ads like these which state in very strident tones that a drug is bad and that if “you or a loved one has had a serious bleeding problem” contact 1-800-BAD DRUG and see if you are eligible for compensation.

These drugs are not bad and the only reason these advertisements are being played is that tort lawyers sense an opportunity to make money.

To understand why they are flooding the TV market now I will have to give you some background on atrial fibrillation , stroke and the drugs available to reduce stroke risk.

Preventing Stroke Associated With Atrial Fibrillation

Patients with atrial fibrillation are at increased risk of stroke and since the 1950s the only drug available for doctors to reduce clot formation in the heart and susbsequent strokes was warfarin (brand name Coumadin). 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 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.

Novel Anticoagulants

In recent years, three 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

Differences Between Warfarin and the Novel Anticoagulants

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 none for the newer drugs. 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 Pradaxa Bad Drug Ads

Beginning about a  year after Pradaxa was released advertisements paid for by law firms seeking “victims” of Pradaxa  identical to the ones we are now seeing for Xarelto began to appear.

The Pradaxa ads went away in mid 2014 when these lawsuits were settled and almost immediately the lawyers began paying for Xarelto ads. Xarelto was the second “novel anticoagulant) to be approved by the FDA and, similar to Pradaxa, was proven to as effective as warfarin in preventing strokes with a similar rate of serious bleeding complications.

As the Wall Street Journal noted (with the catchy title “The Clot Thickens” and opening line “Is a blood thinner causing lawyers to smell blood?”)

“Spending (on Xarelto ads)  jumped to $1.2 million in July from just $8,000 in June, according to The Silverstein Group Mass Tort Ad Watch, which noted the number of ads that ran in July exceeded 1,800. …

The spending increased shortly after Boehringer Ingelheim, which sells a rival blood thinner called Pradaxa, last May agreed to pay $650 million to settle about 4,000 lawsuits over claims the drug caused serious bleeding episodes. The settlement likely emboldened attorneys to turn their sights toward Xarelto which, like Pradaxa, is one of a relatively new batch of blood thinners.”

The third drug to be approved for preventing strokes in atrial fibrillation was Eliquis. Data from the large, randomized study comparing it to warfarin suggest that it is more effective at preventing stroke than warfarin and significantly less likely to have bleeding complications. However, I predict that within the year (especially if the Xarelto lawsuits also are settled by its manufacturer) we will start to see lots of TV ads telling us that Eliquis is a BAD DRUG.

It’s important to remember that all drugs have benefits and side effects. Seemingly harmless antibiotics can increase your risk of dying suddenly (see here), rupturing your achilles tendon or developing a life-threatening colitis.

Xarelto is not a BAD DRUG. When prescribed to appropriate patients with atrial fibrillation with  appropriate precautions it prevents strokes which are potentially life-threatening or disabling. All blood thinners are two-edged swords: they stop good clots and bad clots.

Ignore The Ads

Patients are better off ignoring both positive, direct to consumer, advertisements, promoting these newer anticoagulants and negative, greedy-lawyer sponsored advertisements, soliciting “victims”.

Hopefully when your doctor discusses the choices of blood thinners with you he will present to you a balanced discussion of the pros and cons both of whether or not to take  a blood thinner and whether to take the old standby warfarin or one of the newer agents. An interactive discussion should follow in which your particular issues and concerns factor into the final decision.