Although individual patients respond differently to treatment with the anti-platelet medication clopidogrel (brand name Plavix®), those variations appear normal and may not indicate important differences in the effectiveness of treatment, according to a new study (PDF file) in the Jan. 18, 2005 issue of the Journal of the American College of Cardiology.
“There is nothing unique about clopidogrel, that’s the whole message, in terms of response variability. As with any agent, there are certain people who respond a lot and certain people who respond not a lot. But when you collect large numbers, you see that most people have a normal response, the vast majority have a very nice anti-platelet response on clopidogrel,” said Victor L. Serebruany, MD, PhD, at the HeartDrug Research Laboratories in Towson, Maryland.
In order to investigate reports that some patients were not responding to treatment intended to prevent heart attacks or strokes caused by blood clots, Dr. Serebruany and colleagues at the University of Kentucky in Lexington; Duke Clinical Research Institute in Durham, North Carolina; and the Cleveland Clinic in Ohio analyzed data they had collected over more than seven years during a variety of studies of clopidogrel.
“People started claiming enormously important clinical conclusions, which were based on very vague and very uncertain things,” Dr. Serebruany said.
The data included the results of blood tests that measured how blood platelets aggregated, or clumped together, following treatment with clopidogrel. The study subjects were 94 healthy volunteers, 405 patients treated after coronary stenting, 25 patients with heart failure, and 20 patients treated after strokes. Out of the 544 subjects, 23 (4.2 percent) had a much higher than normal response, while the blood of 26 (4.8 percent) subjects showed very little change in platelet aggregation despite clopidogrel treatment.
An abnormally strong response (hyperresponse) to clopidogrel could raise the risk of bleeding, while a lack of response (hyporesponse) may mean a patient is not adequately protected against dangerous blood clots. However, Dr. Serebruany emphasized that this study did not look at actual health outcomes, and that a low or high response to this laboratory blood test does not necessarily mean a patient is not getting the appropriate benefit from clopidogrel. In addition, he noted that this report was based on combining data from different types of patients and healthy volunteers in studies that were not designed to look at variations in platelet response; so important questions remain to be answered.
“A trial to prove or disprove that certain platelet characteristics have an association with better or worse clinical outcomes absolutely must be done,” he said.
Nevertheless, Dr. Serebruany stressed that large trials involving thousands of patients have demonstrated that clopidogrel can prevent heart attacks, strokes and deaths; so it is premature to alter patient treatment based simply on tests of platelet response.