Safety of drug-eluting stents questioned

Drug-eluting stents linked to increased overall mortality, cancer mortality and Q-wave MI.

BARCELONA — Drug-eluting stents may be associated with an increased risk of mortality, according to two meta-analyses presented at the World Congress of Cardiology 2006, held here last month.

The studies indicated that drug-eluting stents may be linked to increased rates of overall mortality, cancer mortality and Q-wave MI. The data presented from these studies quickly became a much discussed topic at the meeting, and cardiologists began questioning the long-term safety of drug-eluting stents.

Concern was particularly high for cardiologists in some parts of Europe and North America, where drug-eluting stents now account for the majority of stents used to treat patients.

Increased risk

The first study, presented by Edoardo Camenzind, MD, from the University Hospital in Geneva, was a meta-analysis of nine previous clinical trials that examined both the sirolimus-eluting coronary stent (Cypher, Cordis) and the paclitaxel-eluting coronary stent (Taxus, Boston Scientific). Each trial program, comparing these drug-eluting stents with the traditional bare metal stents, was analysed separately.

Camenzind examined up to four-year follow-up data and found that in trials comparing the sirolimus-eluting stent with bare metal stents, the rate of mortality and Q-wave MI among patients treated with sirolimus-eluting stents was 6.3% vs. 3.9% for patients treated with bare metal stents.

For trials comparing the paclitaxel-eluting stent to bare metal stents, the rate of mortality and Q-wave MI was 2.6% among patients treated with a paclitaxel-eluting stent and 2.3% among patients treated with a bare metal stent.

“Death and Q-wave myocardial infarction — the inclusive clinical surrogate of stent thrombosis — have a higher incidence in first generation drug-eluting stents as compared to bare metal control stents,” Camenzind said. “Excess of clinical events appears to be seen with both types of stents. However, the magnitude of these events seems uncertain.”

Meta-analysis on mortality

The second study, presented by Alain Nordmann, MD, from the Basel Institute for Clinical Epidemiology in Basel, Switzerland, was a meta-analysis of 17 previous clinical trials that examined both the sirolimus-eluting coronary stent and the paclitaxel-eluting coronary stent with traditional bare metal stents.

Nordmann examined cardiac and noncardiac mortality among patients treated with drug-eluting stents and bare metal stents. Nordmann observed a trend toward increased mortality in patients treated with drug-eluting stents and a significant increase in noncardiac deaths associated with sirolimus-eluting stents after two and three years of follow-up. There was a total of 36 noncardiac deaths; of these, 15 were due to cancer, including lymphoma and cancers of the lung, prostate, pancreas, kidney and rectum.

This difference could not be demonstrated for the paclitaxel eluting stent.

Effect on patients and practices

George Vetrovec, MD, chairman of the division of cardiology at the Medical College of Virginia in Richmond, and member of the Cardiology Today Editorial Board, said these results may affect cardiologists’ practices in the United States, but cautioned that more data are needed before widespread changes are made.

“The most important issue yet to be specifically addressed is whether this is a class effect or more related to one drug or stent,” Vetrovec told Cardiology Today. “There is some evidence suggesting this may be more related to one stent product.”

Vetrovec added that doctors treating patients with drug-eluting stents should not immediately change their treatments. “My recommendation is to continue [these treatments] for at least one year,” he said.

“If the patient needs to stop for some reason, the cardiologist should stop the antiplatelet agents one at a time, separated by at least one week, to avoid any potential rebound. Furthermore, any symptoms should prompt immediate evaluation.” – by Jay Lewis

Dr. Vetrovec has consulted to Boston Scientific (CEC committee) and Cordis (advisory board and speaker) in different capacities. His program has received fellowship funding from Cordis.

For more information:

• Camenzind E. Safety of drug-eluting stents: A meta-analysis of first generation drug-eluting stent programs.
• Nordmann A. Safety of drug-eluting stents: Insights from a meta-analysis.
• Both presented at: The World Congress of Cardiology 2006; Sept. 2-6, 2006; Barcelona.