Posted by medconsumers on October 1, 2006
A Failed Solution to an Iatrogenic Problem
The long-term safety of drug-releasing stents implanted during angioplasty has been called into question. These tiny wire-mesh tubes emitting low doses of a powerful drug are now the predominant means of propping open a constricted coronary artery in the U.S and many other countries. Called drug-eluting stents by their makers, they show a slightly increased mortality and a higher rate of serious adverse events in longer follow-ups of trials in which participants were implanted with either a drug-eluting or an uncoated stent.
This was announced at the World Congress of Cardiology 2006 held last month in Barcelona, Spain and reported worldwide by UPI and other wire services. The findings have huge implications for the estimated 800,000 Americans who have had a drug-eluting stent implanted and for the multi-billion dollar business that artery-opening has become.
At the Barcelona meeting cardiologist Salim Yusuf, MD, McMaster University, Hamilton, Ontario, gave “a thundering indictment” of artery-opening procedures, according to the cardiology Web site, www.theHeart.org. “The whole field of angioplasty has been led astray by a preoccupation with restenosis [re-narrowing of the artery after angioplasty], for which study after study has shown no prognostic value. We’re chasing problems that are iatrogenic that naturally would not exist in people. We’ve had a perverse financial incentive on the practice of cardiology. It is time to stop and reevaluate.” (That angioplasty* and bypass surgery are not very effective in preventing future heart attacks was explored in the April 2006 HealthFacts “Dramatic Rise in Cardiac Procedures, But No Drop in Heart Attack Rate.)
Dr. Yusuf’s point was lost in the ensuing media coverage of the serious adverse events that showed up in the longer follow-ups—two to four years—of people given drug-eluting stents in clinical trials that compared them with people given uncoated stents. All were company-sponsored trials by Boston Scientific (Taxus stent) or Johnson & Johnson (Cypher stent).
Two separate analyses of the combined results of these trials were described at the Barcelona meeting by Edoardo Camenzind, MD, University Hospital in Geneva, and Alain J. Nordmann, MD, University Hospital, Basel, Switzerland. “What we saw in the long term was more deaths and MIs [heart attacks] in the groups with the first-generation drug-eluting stents,” said Dr. Carmenzind.
Dr. Nordmann’s analysis showed that the people implanted with a drug-eluting stent did better at one year, but there was “a trend toward increased mortality” with drug-eluting stents at up to four years of follow-up. People implanted with a Cypher stent fared worse than those with a Taxus stent in this analysis. They had a higher rate of non-cardiac mortality and serious adverse events than the people with a Taxus stent. Within two days of the Barcelona meeting, Boston Scientific and Johnson & Johnson each released results of one trial claiming safety for its stent and advantages over the uncoated stent. This hasty release of data was, no doubt, intended to counter the negative press from Barcelona.
Shortly thereafter, Boston Scientific did an about-face. The company announced by way of The Wall Street Journal that its Taxus stent does in fact show a slightly higher rate of “late stent thrombosis [potentially fatal blood clots].” The announcement was based on the company’s own reanalysis of its trials. Stent thrombosis should not come as news to Johnson & Johnson because the FDA sent a warning letter to doctors about it months after the Cypher stent was approved in 2003. The following year, Boston Scientific had to recall 99,200 stent systems because of a defect that made it hard, in some cases, to deflate the balloon used to implant the stent. The defect was linked to three deaths and 47 serious injuries.
Stents were introduced after studies showed that about 40% of the coronary arteries close up again (restenosis) in the 6-12 months after angioplasty. This procedure involves the threading of a catheter to the constricted section of a coronary artery and then inflating a balloon at the tip of the catheter to compress the plaque or fatty deposits against the lining of the artery. The introduction of stents, mounted on the balloon catheter, was the intended solution to restenosis. Once the balloon is inflated, the stent expands and is pressed permanently into the inner wall of the constricted portion of the artery.
But physicians found that tissue growth around the stent caused restenosis. Drug-eluting stents were developed to prevent this problem. The Taxus stent emits paclitaxel, an anti-cancer drug that has anti-inflammatory effects. The Cypher stent emits sirolimus, an immunosuppressive drug. These stents reduce but do not eliminate the possibility of restenosis. Once implanted, people go on anti-clotting drugs (aspirin, Plavix) for the rest of their lives.
Bottom Line: Though constricted coronary arteries are not the cause of future heart attacks (as outlined in April 2006 HealthFacts), a lucrative industry has built up around opening them. Because restenosis is common after angioplasty, drug-eluting stents were approved by the FDA in 2003 to reduce the risk. Approval was based on company-sponsored trials that lasted 6-24 months and an agreement that participants will continue to be followed to five years. The companies did not have to prove that their stents were better than drugs in reducing heart attacks. Instead, they merely had to prove drug-eluting stents are better than uncoated stents in avoiding restenosis. Longer follow-up data from these trials formed the basis of two new analyses that found potentially fatal blood clots are not as rare as previously thought. These analyses, however, remain to be confirmed as they have not yet been published.
In his role as discussant at the Barcelona meeting, Dr. Yusuf, the Canadian cardiologist who delivered the thundering indictment of his profession, summarized the situation: “With about six million of these procedures done [worldwide], isn’t it a terrible indictment of our system that we don’t know the safety of these things?”
What to do:
- If you have had a stent (or other type of medical device) implanted, get the name of the manufacturer, the type of stent, and model number. Keep this information in your personal records in case a defect is reported in the future.
- If you had a drug-eluting stent implanted, consult your cardiologist about the need for anti-clotting drugs and the danger of stopping them. Last year the FDA issued a warning that it had received an unspecified number of reports of heart attack, stent thrombosis, and death that occurred in people “who received a drug-eluting stent and then stopped taking their antiplatelet [anti-clotting] medication prematurely.” Some were told by their practitioners to stop the medication prior to undergoing a surgical or dental procedure, others stopped on their own.
- Web casts from the September 2-5 Barcelona meeting can be accessed at the World Congress of Cardiology www.worldcardio2006.org.
*Angioplasty is lifesaving for those who receive the procedure while in the midst of a heart attack.
Maryann Napoli, Center for Medical Consumers ©