Tuesday, September 05, 2006

An "epidemic of madness" - is the game up for drug eluting stents?

Drug-eluting stents used to prop open blocked arteries may lead to an increased risk of death and cardiac events compared with their bare metal counterparts, according to two meta-analyses presented at the World Congress of Cardiology in Barcelona, Spain.

One study found evidence to suggest a significant increase in death and heart attacks in patients receiving Johnson & Johnson's Cypher (sirolimus) stent, and a trend towards an increase with Boston Scientific's Taxus (paclitaxel) product, while the other study indicated that drug-eluting stents might increase non-cardiac mortality.

The researchers behind the studies postulate that, while the drug-coated stents have provided dramatic reduction in the rate of restenosis, or re-blocking of the arteries, they prevent tissue growing over the stent that can form a lining that prevents the metal from stimulating blood clots.

This 'late thrombosis' is a recognised problem with drug-eluting stents, and has prompted a lot of debate about how long antithrombotic therapies such as aspirin and Bristol-Myers Squibb and Sanofi-Aventis' Plavix (clopidogrel) should be used in patients receiving these devices.

It also prompted calls at the WCC to rein in the use of first-generation drug-eluting stents from the likes of eminent cardiologist Salim Yusuf of McMaster University in Canada, who described the take-up of these products as an 'epidemic of madness' to journalists.

The first study, presented by Edoardo Camezind of the University Hospital Geneva in Switzerland, examined four clinical trials comparing Cypher to bare metal stents, involving more than 3,000 patients, and four trials of Taxus involving around 3,500 patients.

The rate of total mortality and a form of heart attack known as Q-wave myocardial infarction combined was 38% higher with Cypher, which was a statistically-significant result (p=0.03), while there was 16% higher incidence with Taxus which failed to reach statistical significance.

In the second study, Alain Nordmann, from University Hospital Basel in Switzerland, conducted a meta-analysis of 17 trials that compared both sirolimus- and paclitaxel-eluting stents with bare metal stents in their effect on total, cardiac, and non-cardiac mortality.

They found that, although there was a trend to benefits with the drug-eluting stents for reducing total mortality at one year compared with bare metal stents, which would be consistent with their robust effects in preventing restenosis, there was a worrying trend to increased mortality in years two, three and four.

Furthermore, at two and three years' follow-up, there was increased non-cardiac mortality with the sirolimus-eluting stent versus the bare metal stent, the majority of which related to cancer. But cardiac mortality did not differ between either drug-eluting stent and the bare metal stents.
At a press conference Nordmann said that securing the raw data from the trials from the stent manufacturers had been difficult, and he called for independent groups to conduct prospective studies of drug-eluting stents to settle the issue of late thrombosis and long-term mortality.

Source: PharmaTimes

Insider's views: A memorable phrase - "an epidemic of madness"! The FDA and other regulators should demand this data urgently.

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