My experience using Xarelto™ reveals how complex drug decisions can be during stroke recovery. The same drugs critical to your survival in the acute phase (e.g., in the hospital right after the stroke) might actually be undermining your full recovery. Let me begin by saying that at the time I am writing this I am 2.5 years post-stroke, and what is discussed in this article applies to the recovery phase, not the acute phase, of an ischemic, not hemorrhagic, stroke.
Physicians treating patients with atrial fibrillation (AF), a frequently suspected cause of ischemic stroke, have enthusiastically embraced the new novel oral anti-coagulants (NOAC), including dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis). “By the end of the study period [2012-2013], novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. – Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant” [1].
Xarelto – New anticoagulant drug for stroke prevention.
About a year after my stroke, my physician specialists starting talking about Xarelto, a new NOAC. My wife and I started researching NOACs and how they compare with warfarin (Coumadin). NOACs and Coumadin often referred to as “blood-thinners, but they do not thin the blood, they make the blood less prone to clotting (i.e., increase the time it takes for the blood to clot), each using a different biochemical approach.
NOACs and Coumadin are believed to lessen the likelihood of a blood clot forming in the atrium of the heart and potentially causing an ischemic stroke, particularly when the heart is beating irregularly due to AF. As you might expect with a drug that reduces blood clotting, there is an increased risk of bruising and bleeding with both NOACs and Coumadin, including intracranial (within the skull) bleeding which is frequently life threatening (some studies have shown intracranial bleeding risk is lower for NOACs than Coumadin, but the evidence is not yet compelling or conclusive).
Coumadin has been widely used for many years and is very inexpensive, but requires monthly blood INR tests at the doctor’s office for clotting time and has dietary restrictions. Basically, Coumadin’s anticoagulant properties are affected by food, while NOACs are believed to not be affected my foods. The Coumadin dietary restrictions require the patient to be consistent in the amount, and not overly indulgent, in their eating of leafy green vegetables and other foods rich in vitamin K (many people mistakenly believe you can’t eat greens while on Coumadin). Coumadin has an “antidote” available to rapidly restore normal clotting time in an emergency setting.
NOACs have been available about 2 years and are expensive relative to Coumadin. NOACs do not require monitoring clotting time (there is no approved test anyway) and have “no known dietary restrictions.” Although there have been hints in the research that NOACs may be more effective than Coumadin, NOACs are currently considered “non-inferior” to Coumadin in preventing ischemic strokes. There is no antidote for NOACs to restore clotting to normal levels and stop bleeding (there are emergency room protocols being developed that are believed to be helpful). Since it is currently believed no monitoring is required, there is no test, such as an INR test, for how clotting time is affected by NOACs. Some studies have indicated NOACs have a “rebound” effect where the risk of stroke increases beyond pre-NOAC-use levels in the period immediately after discontinuing a NOAC. The only approved protocol for getting off a NOAC is to switch to another NOAC or Coumadin. Fortunately, if your kidneys are working well, NOAC’s are mostly removed from the body quickly, in a little as a day, but that may not be fast enough in a serious bleeding event. If your kidneys are not working well, the dose of NOAC often must be adjusted.
Since the overall benefits and risk differentials between NOACs and Coumadin do not appear to be compelling in favor of one over the other, physicians’ enthusiasm for NOACs was a bit inexplicable to us, so we began our research focusing on this issue.
First we realized that when the clinical studies are suggestive rather than definitive, as they typically are with a new class of drugs due to the time and number of studies required to develop conclusive results, physicians often turn to more pragmatic criteria as long as the studies are tending toward favorable conclusions. Pragmatic criteria include cost, convenience, side effects, etc., which translate into patient compliance. Physicians know that for any drug to be effective the patient must take the drug and continue its use as prescribed. Therefore, everything else being roughly equal, it is quite reasonable and responsible for physicians to be favoring a drug that is likely to have a high compliance profile. NOAC’s lack of required monitoring and dietary restrictions clearly fit the bill for encouraging compliance. Also, there are fewer reported side effects (beyond what’s expected with anti-coagulants) with NOACs, but as we learned this can be simply because the drug is too new for side effects to manifest, and be reported and confirmed.
The Role of Standard of Care
Compliance was never an issue for me, but physicians are heavily influenced by the “standard of care” (SOC). SOC is a good thing that has protected patents for half a millennia from physicians and practitioners who were overly enthusiastic, corrupt, incompetent or all of the above. Since things are rarely cut and dry in medicine, for physician groups, and increasingly the government, insurance companies, and other stakeholders, a standard treatment protocol is defined for specific medical conditions.
Problems develop with a standard treatment protocol because it is developed based on a “standard” patient. Initially this was not a major problem because physicians generally knew their patients well and had a lot of discretion to adapt the standard treatment protocol to individual patient needs. However, as medical institutions grew and became more commercial, physicians came to know their patients less well. As medicine became more litigious, physicians became more wary of exercising their discretion to deviate from the standard treatment protocol.
Recently this problem has reached a crisis level because government and insurance companies are “rating” physicians on their compliance with treatment protocols. A SOC poor compliance rating can adversely affect a physician’s practice in a number of ways, including reduced reimbursement, lower approved rates, and less freedom to refer patients to specialists and procedures without prior approval, increasing patient and physician inconvenience and undermining the physician’s practice.
A recent article in the New York Times, “How Medicine Is Being Corrupted“, summed it up nicely: “Contracts for medical care that incorporate “pay for performance” direct physicians to meet strict metrics for testing and treatment. These metrics are population-based and generic, and do not take into account the individual characteristics and preferences of the patient or differing expert opinions on optimal practice.” [2]
There is a strong argument for SOC being more valuable than ever especially when the cost of medicine enters the argument. But if you are not the standard patient, SOC may not lead to the right care for you and you may not be able to depend on your physician to intercede.
This really became apparent when my general practitioner, who has known me well for many years, said if your stroke specialists recommend anti-coagulant therapy, she would recommend Coumadin. She would write me a prescription for a home INR test kit because she knows I would be so compliant that I would test my INR every day. She also knew I was training to get back to triathlon which included riding a road bike in traffic which made Coumadin’s antidote to stop bleeding in an emergency, like getting hit by a car, an important advantage over a NOAC perhaps unique to me as a 60 year old recovering from a severe stroke training for a triathlon. The specialist physicians (neurologists, cardiologists, et. al.) kept urging me to choose a NOAC because it was the new SOC, the latest and greatest, and strongly suggested early research was indicating the NOAC were most likely to help me not have another stroke. After years of exhaustive therapy and training with a long way still to go, preventing another stroke was something of compelling interest to me.
Another example of how the standard of care can put a non-standard patient at risk occurred during the critical acute phase of my stroke. The SOC dictates that acute stroke patients be given a beta blocker to reduce blood pressure. My blood pressure was high during the stroke and I certainly needed it to be treated, but I have a long and troubled history with beta blockers. One long proven effect on me was to dramatically lower my pulse, often a good thing in the trauma of stroke onset. But I wasn’t your standard 60-year old. I was a very fit nationally-ranked triathlete whose resting pulse was 50 bpm. Beta blockers cause my heart rate to plummet to dangerous levels. Plus, all the patient monitoring gear is set to alarm when a patient’s pulse drops below 50, so my caregivers and I were already dealing with constant and ongoing alarms. This generated a lot of attention to my low resting pulse, but it still was not enough to overcome the SOC.
My long-time cardiologist knew this beta blocker issue well and attached a large sheet to the front of my chart that said in giant letters “No Beta Blockers.” Nevertheless, my wife had to be sure to be at my bedside for the first 2 days after my stroke at EVERY shift change to advise the next nurse to not administer a beta blocker (it was the standard of care). This is when I first became aware of the power and problems of the SOC in modern medicine. I would face this again with anti-coagulants.
Historically doctors tend to be biased in favor of every patient being more similar than different. They have an old saying; “If you hear the sound of running hoofs, it’s probably a horse, not a zebra.” I believe this is because statically it’s true and if you start thinking there are wide differences in individuals, the combinations and permutations of possible pathologies are simply overwhelming. Health care providers believe considering the possibility of a zebra leads to unnecessary and costly diagnostic testing. Contrasting this is the emerging evidence that genetics, epigenetics, lifestyle, and accumulated systemic disease result in real differences among patients. Doctors are starting to feel uncomfortable with the SOC mandating the doctor must treat you as if you are always a horse and never a zebra [3].
I did not get tPA and was initially on Plavix for 6 months after my stroke, but I had gone 1 year without any anti-coagulation therapy. In the then 18 months since my stroke I hadn’t had a single stroke onset symptom such as a TIA, blurred vision, slurred speech, or loss of feeling. I was sleeping through the night, maintaining normal weight, back to riding my bike, swimming and making long walks (no running yet) and feeling very healthy despite my loss of function. The strong recommendation of several trusted physicians and the SOC is very powerful and persuasive. Therefore, 18 months after my stroke I started taking Xarelto.
At the time the listed side effects were intracranial bleeding (common to all anti-coagulants), increased bruising, slower cessation of bleeding, and gastro-intestinal bleeding and discomfort. Pretty much like you would expect from an anti-coagulant. For the first 3 months everything went smoothly with only a mild increase in bruising, slower cessation of bleeding, and gastro-intestinal discomfort, about the same level as when I was on 325 mg daily of aspirin. Two things did warrant my attention in that my stools got very dark, almost black, right from the start and my progress in my physical fitness program started to lose ground (I was using Strava.com and various Garmin devices to track every detail of my fitness progress), which had previously been steadily improving.
These side affects were pretty much what was expected and seemed manageable, and a fair trade-off for the reduced probability of another stoke. As time went on, gradually, almost imperceptibly, other things that were not expected started to happen, serious things that I was not watching for because they were not (yet) listed as Xarelto side effects. These side-effects and their profound implications for stroke recovery will be covered in Part 2 of this article.
[1] Patterns of Initiation of Oral Anticoagulants in Patients with Atrial Fibrillation – Quality and Cost Implications – http://www.amjmed.com/article/S0002-9343(14)00399-4/abstract
[2] How Medical Care Is Being Corrupted, Pamela Hartzband and Jerome Groupman – Nov. 18, 2014 – http://www.nytimes.com/2014/11/19/opinion/how-medical-care-is-being-corrupted.html?ref=health
[3] Is there any room for individuality in medicine? http://www.kevinmd.com/blog/2014/10/room-individuality-medicine.html
Overcoming Stroke 