Furthermore, the researchers said, about one-third of the new stents were placed in patients with clinical characteristics for which such stent use has not yet been approved by the Food and Drug Administration (FDA). However, the researchers said that their finding of a high rate of "off-label" usage should be seen more as an impetus for further clinical trials rather than an immediate safety issue, since cardiologists have been placing traditional stents for more than 10 years and are comfortable with the procedure.
Stents are tiny mesh tubes that are inserted into the site of a blockage in a coronary artery that has been opened during balloon angioplasty. However, a principal complication of the procedure has been the high rate of treated arteries becoming blocked again, a process known as restenosis.
In an attempt to improve stents to keep treated arteries open, stent manufacturers coated them with a chemotherapeutic agent that limits the formation of scar tissue inside the artery. So far, clinical trials have shown that these new stents can reduce the restenosis rate to single digits from the 20 to 30 percent rate of the older stents. The first drug-eluting stent received FDA approval in April, 2003.
"Drug-eluting stents are truly breakthrough products in treating coronary artery disease, and in our analysis of the early trends of the their use, we found disparities in terms of age, race and socio-economic factors," said Duke cardiologist Sunil Rao, M.D., who presented the results of the Duke analysis Nov. 10, 2004, at the American Heart Association's annual scientific sessions in New Orleans.
"We also found that the rate of increased usage for off-label use was almost identical to that on-label use, but the incidence of short-term adverse effects associated with these uses was low," he continued. "This suggests that there needs to be randomized clinical trials to study the long-term safety and effectiveness of drug-eluting stents in these particular patients."
For their study, the Duke team analyzed data collected by the American College of Cardiology National Cardiovascular Disease Registry (ACC-NCDR). This database collects clinical and outcomes data on angioplasties performed at 259 sites across the U.S.
Since the Duke analysis covered the last nine months of 2003, the only drug-eluting stent approved for use in the U.S. was the Cypher (tradename) stent, produced by Cordis, Miami Lakes, Fla. The only other approved drug-eluting stent (tradename Taxus), produced by Boston Scientific, Cambridge, Mass., did not come to market until March, 2004, and therefore is not a part of the current study.
For the last nine months of 2003, the results of 162,969 angioplasty procedures were entered into the registry, with 83 percent of them involving the placement of a stent.
"During that period, 35 percent of all angioplasties involved the placement of drug-eluting stent," Rao said. "The growth from quarter to quarter was dramatic, rising from 19.5 percent in the second quarter, 39.4 percent in the third quarter and 45.3 percent in the last quarter."
When the researchers analyzed who received these next-generation stents, they found that older patients, African-Americans and patients without insurance were more likely to have received the older, bare metal stents.
"Additional studies are needed to determine whether these differences are related to anatomic differences, socio-economic factors or physician bias," Rao said.
In terms of where treatment was provided, the researchers found that university affiliated or teaching hospitals and those with a higher volume of angioplasties were more likely to be using the newer stents.
When the FDA gave its approval, it recommended that drug-eluting stents were to be used initially for fairly straightforward cases of blocked arteries, as was tested in the devices' clinical trials. However, just as is the case with prescribing medications off-label, physicians are free to place stents in any patient.
Of all the drug-eluting stents used during the study period, 33 percent were placed into patients who were considered off-label. These patients had either suffered from an acute heart attack, already had an occurrence of restenosis, had received coronary bypass surgery, or had severely occluded arteries.
The researchers found similar growth rates during the three quarters measured for the off-label and on-label usages.
"Although the growth rates of the two indications were similar, the off-label accounted for less than one quarter of the cases in the registry," Rao said. "This suggests that overall, cardiologists were following the on-label indications. The in-hospital outcomes were the same for off-label indications, but it is concerning that off-label use grew so rapidly without data from clinical trials to justify their use in these cases."
The study was supported through the ACC-NCDR.
Other members of the team were Eric Peterson, Duke; Richard Shaw, Sutter Pacific Heart Centers, San Francisco; Ralph Brindis, Kaiser Hospital, San Francisco; Lloyd Klein, Rush University Medical Center, Chicago; and William Wientraub, Emory University, Atlanta.