Drug Coated Stents Have Risk of Life-Threatening Side-Effects. John Wehr couldn’t believe what was he was reading. An article on drug-coated stents, the kind used to prop open his two clogged coronary arteries last June, said the devices have a ”small but significantly increased risk” of life-threatening side-effects.
Worried, the 78-year-old retired Bethlehem Steel Corp. accountant clipped the article and called his cardiologist. He wasn’t alone.
Drug-coated stents tiny mesh tubes coated in chemotherapy drugs have been considered the best medicine had to offer, superior to the uncoated variety in their ability to keep scar tissue at bay and prevent coronary arteries from reclosing.
They’ve been inserted in 6 million heart patients nationwide, including 5,000 in the Lehigh Valley.
But heart specialists have been forced to reconsider their use since December, when new research showed they are more likely to cause blood clots than do the bare-metal variety and the clots can appear six months to years after the stents are placed.
Clotting is a natural reaction to injury, but studies conducted in the United States and Sweden found that blood clots were getting stuck inside the stents, cutting off blood flow and causing heart attacks and sudden death. Researchers put the risk of developing clots at about 1 in 200-500 people.
Area cardiologists said they’ve found blood clots in the drug-coated stents of patients who survived heart attacks. And they can only presume that some others have died from the complication as well. Without autopsies, they can’t know for sure.
Rapid escalation of use of the devices has only added to the alarm. Since they went on the market four years ago, drug-coated stents have far surpassed bare metal, becoming the stent of choice in 80-90 percent of all cases.
”It’s a huge amount,” local cardiologist Bryan Kluck acknowledged. At Lehigh Valley Hospital-Cedar Crest, where Kluck practices, cardiologists inserted the devices in about 1,700 patients last year. Over the same time at St. Luke’s Hospital-Fountain Hill, about 1,000 patients received one or more drug-coated stents. Another 500 or so received the devices at Easton Hospital in Wilson.
In response to the findings, the American Heart Association, American College of Cardiology and other medical groups in early January recommended that most patients with drug-coated stents remain on anti-clotting medicines, such as the prescription drug Plavix, and aspirin, for at least a year, possibly indefinitely.
Experts believe continued use of anti-clotting medicines is the best recourse because research shows that patients who stayed on the drugs for a year fared the best among those studied. The 3-5 percent increased risk of blood clots occurred primarily among patients who stopped taking the medicines after six months.
Patients were supposed to stay on the pills for one to six months, depending on the type of stent used. However, one study showed the average time patients took the blood-thinners was 45 days.
”The increased risk [of blood clots] is very small and likely to be overcome if patients stay on anti-clotting medicines,” noted Dr. Deepak Bhatt, a cardiologist and researcher at the Cleveland Clinic, which analyzed 14 studies involving drug-coated stents.
Promising, but not perfect
Two brands of drug-coated stents are used in the United States: Taxus by Boston Scientific Corp. and Cypher by Johnson & Johnson’s Cordis Corp.
Placed inside a blocked coronary artery on the end of a deflated balloon, the stents are locked in place when the balloon is inflated. They act as a buttress to keep fatty deposits pinned against the artery wall. They restore blood flow to patients in the throes of a heart attack or who have blockages.
When they first came on the market, the drug-coated stents were recommended only for patients at low risk, such as those with small blockages in single vessels. But because early results with such patients looked so good, doctors used them in more common and complicated cases and in sicker patients.
Doctors had hints of a clotting problem from earlier studies, but it wasn’t until the release of more conclusive data in December, much of it produced by the Duke Clinical Research Institute in Durham, N.C., that concern reached a critical level.
A rare summit of international experts called days later by the U.S. Food and Drug Administration produced the recommendation that patients remain on anti-clotting medication for a year or more.
But Dr. Robert A. Harrington, a professor of medicine in the division of cardiology and director of Duke’s Clinical Research Institute, said the recommendation puts doctors and patients in another predicament.
”Are we committing millions of patients to lifelong [anti-clotting medicine] with its attendant costs and risks?” he asks in an editorial about the blood-clot problems in a December issue of the Journal of the American College of Cardiology.
Plavix generic name clopidogrel and other blood-thinners can cause life-threatening internal bleeding in some patients, such as those with ulcers. It also has been shown to be no better than low-cost aspirin at preventing a first heart attack.
The Cleveland Clinic’s Bhatt, however, doesn’t think the side-effects of blood thinners are reason enough not to continue using drug-coated stents.
”Everything has risks,” he said.
Weighing The Risks
Some patients were so upset by the research that they asked that the stents be removed something doctors generally don’t do, considering it much riskier than leaving the mesh tubes in place.
Cardiologists hope they can quickly learn which patients, beyond the low-risk, are best suited to drug-coated stents from patient registries and continued research. Or that the next generation of stents won’t cause blood clots. In the works are stents with different coatings and others made to dissolve over time.
Until they have more answers, local and national specialists are extending the use of anti-clotting medicine. They also are being more selective in using drug-coated stents, perhaps precluding patients with long blockages or blockages that extend beyond one artery, persons with diabetes, persons scheduled for lung or colon cancer surgery or persons who have trouble keeping up pill regimens.
”There was a time that I’d try any case I could to use drug-coated stents,” said Dr. Gary Costacurta, chief of cardiology at Easton Hospital in Wilson.
Now, Costacurta said, he may use bare-metal stents for patients with long blockages or for patients with blood vessels that are large in diameter.
LVH’s Kluck said being more selective may not be so easy especially in the emergency room.
About 20 percent of the patients who receive stents arrive in the ER with chest pains and signs of imminent danger to the heart. It’s a scenario in which seconds can make a difference, he said, in how much damage occurs to the heart and whether or not the patient lives.
Such cases leave little time for a full patient history, Kluck said. What medicines the patient had been taking or stopped taking and whether they have had bleeding problems in the past might not be known. ”It’s not clear if plain stents are better than drug-coated” for such patients, he said. ”We must probe deeper to know.”
Dr. Peter Puleo, a cardiologist and medical director of the catheterization laboratory at St. Luke’s Hospital in Fountain Hill, said he started telling his patients to stay on anti-clotting medicines for two years when he read early studies suggesting a problem.
Puleo said he uses bare-metal stents on patients with long blockages or larger blood vessels. He said he is less worried about patients bleeding from blood-thinners than he is about heart attack and death from blood clots. ”Death from internal bleeding is even more unusual than late-term thrombosis,” Puleo said, using another term for blood clots. ”In cardiology, more people clot than bleed to death.”
”It makes people nervous about continuing [on the medicines], but you can get through it,” Puleo said.
Dr. J. Patrick Kleaveland, medical director of the catheterization laboratory at LVH and co-director of the lab at Grand View Hospital in West Rockhill Township, Bucks County, said drug-coated stents are still safe and effective in reducing restenosis for patients with simple, straight-forward blockages.
Patients at higher risk may still benefit as well, Kleaveland said, if they can stay on anti-clotting medicines for at least a year without uncontrolled bleeding. ”The patients I’ve seen with the most devastating problems are those who stopped taking their medicines prematurely,” he said.
Reasons patients stop taking anti-clotting medication range from not being able to afford the pills, which cost $3-$4 a piece, to not feeling well on them or having difficulty keeping up with the regimen.
But cardiologists warn that stopping, even for a few days, could prove fatal if the body throws blood clots at the braced vessels.
”The first sign of trouble could be the total blockage of a stent, artery and blood flow,” Kluck said. In other words, a sudden, massive heart attack.
Lehigh County Judge Edward Reibman stopped taking his prescription blood-thinner months after receiving a drug-coated stent in 2005. He counts himself lucky he didn’t develop blood clots.
”When I had the stent put in, I was prescribed Plavix and aspirin, but I felt lousy on them,” Reibman said, remembering muscle and bone pain.
He stopped the Plavix, switched to another anti-clotting drug and after a few months stopped that, too. But he continued taking a baby aspirin a day.
At a checkup in December, when news broke of the risk of blood clots, Reibman’s doctor told him to resume the Plavix.
The judge wonders what new risks will come with the prescription medicine, but said he isn’t judging prior decisions.
”Everyone thought the stents were fine. No one knew about this late stent [blood-clotting] problem then,” he said. ”You make decisions with the best information you have at the time, and as science develops, you learn more and hopefully make more decisions.”