Vast Majority of Patients on Popular Blood Thinners Aren’t Getting the Right Dose
As much as 75 percent of patients taking Plavix and Effient may be prescribed too much or too little, putting them at risk for blood clots or uncontrolled bleeding.
-- by Heather Kathryn Ross
There's no such thing as one size fits all. However, current clinical guidelines suggest giving all patients a standardized dose of the common blood-thinners clopidogrel (Plavix) and prasugrel (Effient).
Millions of Americans with coronary artery disease take these medications to decrease their risk of developing blood clots that could cause a heart attack or stroke. Startling findings by researchers at the Intermountain Medical Center Heart Institute reveal that 75 percent of patients on these medications may be receiving the wrong dose, putting them at risk for future heart attacks or uncontrolled bleeding.
“We’ve found that there’s a wide variability in the extent to which these drugs block platelet activity,” said Dr. Jeffrey Anderson, Director of Cardiovascular Research at the Intermountain Medical Center Heart Institute and co-author of the study. “Based on the literature and our personal experiences, there is an optimal range—a sweet spot, if you will. If you have less than that, you run the risk of clotting and if you have more than that you run the risk of bleeding, especially in high-risk patients.”
The Expert Take
The solution to this daunting problem, according to Anderson, is simple. By using a basic blood test called a platelet function assay, physicians can establish how well a patient’s blood clots with his or her current dose of medication. The dosage can then be adjusted accordingly.
However, Dr. David Brown, a professor in the division of cardiovascular medicine at Stony Brook University urges caution until more research has been conducted. He bases his patient recommendations on Food and Drug Administration (FDA) guidelines, which were determined by clinical trials of these drugs in which all patients received the same dose.
“The research on which approval of those drugs was based did not use individualized dosing,” Brown said. “Thus, there is no evidence that modifying doses would improve efficacy or safety.”
Anderson’s team contends that it isn’t as easy as most doctors think to predict how a particular patient will react to a blood-thinning drug. Common indicators like gender, age, cholesterol levels, and heart health history did not accurately forecast how much medication study participants would require.
Anderson says this is because multiple factors, including genetics, biochemistry, and lifestyle, determine how well these drugs work for each patient. He recommends that, as a next step, a controlled trial be performed in which half of participants are given a personalized dose of blood-thinners, while the other half receive the standard dose. Until such a trial is conducted, Brown says he’ll be sticking to FDA instructions.
“I use the standard, approved doses for these drugs without [blood] testing,” Brown said. “There is some genetic variation in responsiveness to these drugs, but there is no data that adjusting doses to account for these differences improves patient clinical outcomes.”
Anderson’s team claims that by finding the lowest effective dose of blood-thinners for each individual, doctors can help cardiac patients significantly reduce their prescription drug expenses. The cost of a one-year supply of prescription blood thinners is approximately $1800, the study authors say.
In addition, those at the highest risk, such as elderly patients who’ve just had a heart attack, would likely benefit from careful monitoring and a medication regimen tailored to their particular needs.
“Our hypothesis is that we ought to be testing, or titrating, each patient. We call it ‘personalized medicine,’” Anderson said. “For lower risk patients, it doesn’t seem like this makes much of a difference, but it’s going to be worth the extra effort and cost to do this for high-risk patients.”
Until Anderson’s hypothesis is tested in a trial setting, FDA guidelines are unlikely to change, but that doesn’t mean patients can’t err on the side of caution and ask their doctors to test whether blood-thinners are working as effectively as possible for them.
Source and Method
Researchers reviewed the records of 521 patients with coronary artery disease taking either clopidogrel or prasugrel. They found that only 25 percent of patients had a PRU measurement (a measure of blood platelet clotting inhibition) within clinical guidelines.
They determined that half of patients taking clopidogrel were taking too little, raising their risk of blood clots, while an additional 25 percent were taking too much. Similarly, they found that half of patients on prasugrel were taking too much, raising their risk of uncontrolled bleeding, while another 25 percent were taking too little.
The research team will present their findings tomorrow at the American Heart Association’s Scientific Sessions 2012 in Los Angeles.
In 2008, a study published in Cardiovascular Interventions, a journal of the American College of Cardiology, determined that patients with certain alleles (forms of particular genes) required higher doses of Plavix to inhibit platelet function. The authors recommended genotyping in order to individualize the dose of Plavix each patient receives.
In 2010, the FDA added a warning label to Plavix saying that patients with specific genetic differences are “poor metabolizers” of the drug and should be given another medication or a tailored dose of Plavix.