New research finds that the first three months after heart patients stop taking the clot-preventing drug clopidogrel (Plavix) are the most dangerous.
"This is the first study to make this observation," said P. Michael Ho, MD, PhD, a cardiologist at the Denver VA Medical Center and lead author of the report. "We need more studies to confirm it, and see whether and why there is an increase in adverse events after stopping."
The study does not address the issue of how long Plavix may safely be taken, said Dr. Ho, who is an assistant professor of medicine at the University of Colorado. The current recommendation is that it should be used for nine months after a heart attack and 12 months after a stent is implanted to help an artery stay open.
"We looked at people who took different lengths of clopidogrel treatment," Dr. Ho said. "We found a twofold increase in risk in the 90day period after stopping for those who took it less than six months or greater than nine months. For those who took clopidogrel longer than 12 months or 15 months, we could not calculate the increased risk because we did not have enough patients."
Dr. Ho and his colleagues assessed the incidence and timing of death or acute heart attacks in 3,137 people discharged from 127 VA hospitals. The patients were taking Plavix after an acute coronary event, such as a heart attack. The average time of Plavix treatment was 302 days.
Analysis found the incidence of adverse events was higher in the 90 days after the medication was stopped than in the 91 to 180 days after cessation.
"This is going to get a lot of attention, both from doctors and the medical community at large, because clopidogrel is such a widely used drug," said Deepak Bhatt, MD, associate director of the Cleveland Clinic Cardiovascular Coordinating Center.
The finding "follows common sense, but no one has actually shown this before in a large group of patients," Dr. Bhatt said.
The results appear to support the view that longer therapy with clopidogrel is better but does not completely answer that question, he said. "The very necessary next step is to figure out whether longer duration is better in a randomized, controlled trial."
Such a controlled trial would meet the gold standard for medical research. The newly reported study was observational, Dr. Ho noted, meaning that it examined what was happening in medical practice without attempting to single out factors affecting the results.
A decision on whether or when to stop clopidogrel treatment must be made on a case-by-case basis, Dr. Ho said. "The final decision should be left to provider and patient. They have to weigh the risk of discontinuing clopidogrel against the risk of abnormal bleeding if it is continued. The clinician needs to weigh the risk and benefits for each individual patient."
Those making the decision should remember that the risk found in the study was "relatively small," Dr. Ho said. Among the more than 3,000 cases studied, there were 163 adverse events in the 90 days after drug treatment stopped, 57 in the following 90 days, and 26 in the third 90-day period.