The first company to receive FDA clearance for a drug-eluting stent (DES) has released six-year follow-up data on that device. The clinical benefits of the Cypher sirolimus-eluting coronary stent compared to a bare-metal stent (BMS) were sustained, according to data presented Wednesday at the Cardiovascular Revascularization Therapies (CRT) conference in Washington.

The data is significant considering the many ups and downs the DES market has seen in the six years since Johnson & Johnson's (New Brunswick, New Jersey) Cordis (Miami Lakes, Florida) unit received clearance for the Cypher stent. The past six years in DES history has been characterized by data questioning the safety and effectiveness of the devices compared to their bare-metal cousins.

Sidney Cohen, MD, vice president-clinical at Cordis, noted in his presentation at CRT a copy of which was provided to Medical Device Daily that no differences were observed between the Cypher stent and the BMS in the safety measures of heart attack, death or blood clots.

"These data are important for several reasons. First, the six-year results have remained consistent over time and continue to show the sustained patient benefits of the Cypher stent for patients," Cohen said in response to an MDD question. "As the longest running randomized clinical trial of a drug-eluting stent, only the SIRIUS trial can provide six-year clinical data. Second, the results from SIRIUS confirm the overall safety of Cypher over a six year time period and that too is unmatched by any other drug-eluting stent."

At six-year follow-up, patients in the Cypher stent arm of the SIRIUS trial experienced significantly lower rates of target vessel failure (TVF), the primary endpoint of the trial, than those who received the BMS (26.1% for the Cypher vs. 39.9% for the BMS). TVF was defined as a composite of cardiac death, myocardial infarction and target vessel revascularization (TVR, or re-treatment of the blocked vessel).

The sirolimus-coated BX Velocity Balloon-Expandable Stent in Treatment of Patients with De Novo Coronary Artery Lesions (SIRIUS) trial, sponsored by Cordis, served as a pivotal study for the U.S. approval of the Cypher stent in 2003 and is the longest-running, U.S.-based study for a DES.

In the double-blinded, multi-center randomized trial, patients were divided into two treatment groups: 533 patients received the Cypher and 525 patients received a BMS. Of the original 1,058 participants, only about 50% (271 patients receiving the Cypher and 255 patients receiving a BMS) participated in the six-year follow up.

"The six-year results of the SIRIUS trial demonstrate that the treatment benefits and safety of the Cypher stent are preserved in longer-term follow-up," Cohen said. "The Cypher stent remains the most proven and studied drug-eluting stent in its class and physicians can trust in the long-term safety profile and sustained patient benefits associated with the Cypher stent."

In this long-term follow-up, the Cypher stent also demonstrated lower rates of target lesion revascularization (TLR, or re-treatment at the same arterial site) and major adverse cardiac events (MACE), which include heart attack and death, compared to the BMS. The TLR rate for the Cypher stent was 11.9% vs. 27.9% for the BMS, and the MACE rate for the Cypher stent was 22.6% vs. 37.2% for the BMS.

Cohen noted during his presentation that the six-year clinical follow-up was completed on only half of the originally enrolled patients and that, while Kaplan-Meier analysis partially adjusts for this, bias cannot be ruled out, as patients who did receive follow-up were not a random subset of the original cohort.

"It is important to note that both the absolute reduction in key endpoints between the Cypher stent and the control, and the increment in these numbers due to underlying cardiovascular disease progression, remains consistent over the six-year timeframe. This demonstrates there is no 'late catch-up' in the patients receiving the Cypher stent," Cohen concluded.

In addition, there was no significant difference in the mortality or the heart attack rates between the Cypher stent and the BMS at six-year follow-up. The mortality rate was 8.9% for those receiving the Cypher stent compared to 9.4% for those receiving BMS. The myocardial infarction rate for the Cypher was 6.4%, compared to 7% for the BMS.

According to Cohen's presentation at CRT, there was no significant difference in the overall rate of stent thrombosis between the Cypher stent and the BMS, regardless of the definition of stent thrombosis employed. The definitions include the original SIRIUS trial protocol definition and the Academic Research Consortium (ARC) definition. At six years, the protocol definition identified a rate of 1.2% stent thrombosis for the Cypher stent vs. 0.8% for the BMS. The definite/probable ARC definition identified a stent thrombosis rate of 1.2% for the Cypher stent vs. 2.1% for the BMS. There was no trend for an increase in ARC-defined definite or probable very late stent thrombosis rates between 1 and 6 years (0.8% in Cypher arm vs. 1.0% in the BMS arm), Cordis noted.

Last year second-generation drug-eluting stents hit the U.S. market, first Medtronic's (Minneapolis) Endeavor zotarolimus-eluting stent, which won approval in February (Medical Device Daily, Feb. 4, 2008), then with Abbott's (Abbott Park, Illinois) Xience V everolimus-eluting stent getting approval five months later (MDD, July 7, 2008).

Both the Endeavor and Xience are expected to elbow aside the first-generation DES devices, the Cordis Cypher and the Taxus from Boston Scientific (Natick, Massachusetts), which was approved in 2004.

Abbott also supplies a private-label version of Xience V to Boston Scientific called the Promus.

According to Cordis, the Cypher stent has been used to treat some 3 million patients with coronary artery disease. A robust clinical trial program that includes more than 70 studies that examine the performance of the Cypher stent in a broad range of patients, the company said, supports the safety and efficacy of the device.

The next version of a sirolimus-eluting stent, the Cypher Select sirolimus-eluting coronary stent, was launched in Europe, Asia Pacific, Latin America and Canada in 2003. The Cypher Select Plus stent, the third version of a sirolimus-eluting coronary stent, received the CE mark in 2006 and is currently available in many markets outside the U.S.

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