The conflicting studies
At ESC Congress 2006 two independent meta-analyses, presented during a Hot Line session, raised the possibility that first generation DES might increase the risk of death. In one presentation Alain Nordmann from Basel, Switzerland, suggested the sirolimus (but not the paclitaxel) eluting stent was associated with small but significant increases in non-cardiac mortality; while in a second presentation Edoardo Camezind from Geneva, Switzerland, pooled published data from four randomised trials to show rates of overall death and Q wave MI to be higher (6.3%) for the Cypher stent than the BMS stent (3.9%, p=0.03).
The fall-out was immediate. According to data from Morgan Stanley, DES stent penetration in Europe fell from 56.2% in the third quarter of 2006 to 49.4% in the fourth quarter of that year, and to a low of 45.7% in the third quarter of 2007. The decline in DES use was even more dramatic in the USA.
The latest results
In this session, Stefan James from Uppsala Clinical Research Centre, Sweden, will review data from registries, focussing on the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) which analysed outcomes of all the 47,967 patients receiving stents in Sweden between 2003 and 2006.
The updated SCAAR registry, says Adnan Kastrati from the German Heart Centre in Munich, Germany, adds to a growing number of randomised trials, registry studies and updated analyses demonstrating no higher mortality associated with DES than with BMS. “Now, three years after Barcelona 2006, there's abundant evidence to show that the benefit of DES in terms of restenosis is not achieved at the expense of a compromised safety,” says Kastrati.
Trials are now under way in more complex cases, such as acute MI, in-stent restenosis, and complex and long lesions. Recent changes in trial design, says Kastrati, include those enrolling “all comers” to better reflect real life situations, with follow-up lasting at least two years. Moreover, DES technology continues to evolve with new biodegradable polymers for drug release, polymer-free release of drugs, drug-eluting balloon technology and completely biodegradable stents.
Most opinion leaders are agreed the scientific debate sparked by ESC Congress 2006 at least prompted research into stent safety. Since then, an unprecedented wave of published DES safety data in more than 200,000 patients has reassured both physicians and patients that the proven efficacy of first generation DES was not at the cost of safety. Moreover, trial design has changed, placing greater emphasis on safety aspects in the evaluation and approval of newer generation DES.
And at the session delegates will undoubtedly listen with particular attention to Camezind's own presentation simply titled, “Did I repent?”.