The findings of a new study suggest that continuing use of blood thinners, such as Plavix or Effient, for more than 30 months after placement of a stent may decrease the risk of heart attacks and blood clots when compared to only using the drugs for the currently recommended one-year period. However, federal investigators warn that those taking Plavix may face an increased overall risk of death with longer use.
The FDA issued a drug safety communication on November 16, highlighting the findings of recent trial data on the use of antiplatelet blood-thinning therapy in combination with drug-eluting coronary heart stents.
Although long-term use of the blood thinners was found to reduced the risk of side effects associated with stent placement, which may cause blood clots to develop on the stents and potentially break free, traveling to the heart or lungs, the study found that use of Plavix for two and a half years, instead of just one year, may increase the risk of patients dying.
The FDA’s announcement came the same day that the study, the Dual Antiplatelet Therapy (DAPT) trial, was published in the New England Journal of Medicine.
The study was conducted by researchers from around the world, including from Harvard Medical School in Boston, the Imperial College in London, Universite Paris Diderot, in Paris, as well as Duke University, Stanford and others. It was sponsored by a number of drug manufacturers, including Abbott, Boston Scientific, Medtronic, Bristol-Myers Squibb, Eli Lilly, Daiichi Sankyo, and Cordis.
The research was done on the behest of the FDA, involving nearly 10,000 patients who had taken aspirin along with drugs belonging to a class of antiplatelet blood thinners called thienopyridines for a year after receiving heart stents to battle heart congestion. The class includes Plavix, Effient and Ticlid.
After a year on the drugs, all participants in the study were told to continue taking the drugs for another 18 months, but some were given the real thing and others were given a placebo.
Researchers found that taking the drugs had a significant benefit on preventing stent thrombosis, and major adverse cardiovascular and cerebrovascular events; in some case cutting the risks in half. However, the researchers also found that about 2% of the patients who kept taking the drugs for a total of 30 months died, compared to only 1.5% of those taking a placebo. Prolonged use of the drugs also significantly increased the bleeding risks.
“Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding,” the researchers concluded. “An unexpected finding was that the number of deaths from any cause during the treatment period was higher in the group that continued to receive thienopyridine than in the group that received placebo, a difference that was driven by an increase in the number of deaths from noncardiovascular causes in the thienopyridine group.”
The FDA analysis of the findings indicate that the deaths appeared to be related to an increase in trauma and cancer deaths, and only appeared among patients given Plavix. The agency does not know how the drug could be connected with the deaths, and noted that increases in non-cardiovascular death have not been reported in previous large trials involving Plavix. However, the agency concluded that the benefits of taking the drugs for long-term therapy after receiving a heart stent outweighed the risks, but its review of the findings are ongoing.
Plavix Effectiveness Concerns
Plavix (clopidrogrel) is a blockbuster medication that has been used by millions of people in the United States and is commonly prescribed to prevent blood platelets from sticking together and forming clots. There are between 2.5 million and 3 million Plavix prescriptions handed out each month in the U.S.
In recent years, some concerns have emerged about the potential side effects of Plavix and whether many of these prescriptions may have been unnecessary due to genetic resistance to the medication.
While Plavix has been promoted as being better at its job than aspirin, with a cost that is many times higher than aspirin, questions have been raised about the effectiveness of Plavix for many patients and whether it actually provides any benefit over aspirin.
In August 2009, researchers from the University of Maryland identified a gene variant found in about one-third of the population that may signal a reduced effectiveness of Plavix. People with the CYP2C19 variant have reduced functioning of a liver enzyme that is supposed to convert Plavix from its inactive form to its active form, potentially making Plavix ineffective at reducing the risk of blood clots.
Unnecessary use of Plavix may expose individuals to an increased risk of gastrointestinal bleeding, severe ulcers, a rare blood disorder known as thrombotic thrombocytopenic pupura (TTP) and other injuries.
Bristol-Myers Squibb and Sanofi-Aventis currently face hundreds of Plavix injury lawsuits filed in state and federal courts throughout the United States, alleging that the drug makers have placed their desire for profits before the safety of consumers by aggressively marketing the medication while failing to adequately warn consumers or the medical community about the health risks associated with the medication.
In 2013, the U.S. Judicial Panel on Multidistrict Litigation (JPML) centralized all Plavix cases filed in the federal court system before U.S. District Judge Freda L. Wolfson in the District of New Jersey for coordinated handling during pretrial proceedings.