The widely used sirolimus-eluting stent is superior to the second-generation zotarolimus-eluting stent for patients in everyday clinical practice, concludes the SORT OUT III study published Online First and in this week's edition of The Lancet. Treatment with the sirolimus-eluting stent halves the likelihood of a major adverse cardiac event within 9 months of implantation compared with the zotarolimus-eluting stent. Additionally, the sirolimus-eluting stent reduces the need for repeat revascularisation (restoring blood flow in a vessel) and gives a lower risk of heart attack in the 18 months after treatment compared to the zotarolimus-eluting stent, and decreases the risk of thrombosis (blockages) in the first year after implantation.
Drug-releasing (eluting) stents are used for percutaneous coronary interventions (PCI) to help reduce rates of restenosis (re-narrowing) of arteries in patients with coronary artery disease.
Previous studies have questioned the safety of first-generation stents eluting drugs such as sirolimus because of an increased risk of late and very late thrombosis. Second-generation stents releasing agents like zotarolimus were intended to improve safety and efficacy and have been shown to lower rates of restenosis without increasing the risk of stent thrombosis in comparison to bare metal stents. However, trials have been limited to lower risk patients without complex lesions or acute coronary syndromes, and were designed to assess only angiographic late lumen loss (artery re-narrowing due to scar tissue growth) or target vessel failure.
To address these limitations, Jens Flensted Lassen and colleagues from Denmark compared the efficacy and safety (as measured by occurrence of cardiac death, heart attack, and stent thrombosis) of sirolimus-eluting and zotarolimus-eluting stents in a trial designed to reflect routine clinical practice, with broad inclusion criteria involving everyday patients with more complex lesions.
The SORT OUT III study randomly assigned 2332 patients undergoing PCI to treatment with sirolimus-eluting (1170) or zotarolimus-eluting (1162) stents between January 2006 and August 2007. Danish health registries were used to detect clinical events during follow-up.
Over 9 months, patients with the zotarolimus-eluting stent had a doubled risk of major adverse cardiac events compared to those treated with the sirolimus-eluting stent (6% vs 3%). This was mainly the result of a reduced need for target lesion revascularisation in the sirolimus group, but fewer heart attacks and stent thromboses were also observed in the sirolimus group.
At 18 months, the significant difference in major adverse cardiac events between the two groups persisted (10% for zotarolimus vs 5% for sirolimus) and was due to an increased need for target vessel revascularisation and a higher incidence of heart attacks in the zotarolimus group.
All-cause mortality was similar 9 months after treatment, but was significantly different at 18 months (4% for zotarolimus vs 3% for sirolimus)
The authors say: "Findings from our study show that the reduced antiproliferative effect of the zotarolimus-eluting stent results in a decrease in clinically driven efficacy in routine clinical care."
They conclude: "The sirolimus-eluting stent is superior to the zotarolimus-eluting stent for patients receiving routine clinical care."
In an accompanying Comment, Mark Webster and John Ormiston from Auckland City Hospital in New Zealand discuss the trial in the context of other head-to-head comparisons between drug-eluting stents.
Dr Michael Maeng, Aarhus University Hospital, Aarhus, Denmark. T) +45 2670 3237 (mobile) E) michael.maeng@ki.au.dk
Dr Mark Webster, Auckland City Hospital, Auckland, New Zealand. T) +64 9 307 4949 E) mwebster@adhb.govt.nz
For full Article and Comment, see: http://press.thelancet.com/sortout.pdf
Journal
The Lancet