September 29, 2009 – Among the biggest news to come out of TCT 2009 last week was the late-breaking data from the SPIRIT IV trial, which showed Abbott's XIENCE V Everolimus-Eluting Coronary Stent achieved superiority in the key safety and efficacy measures compared to the TAXUS Express Paclitaxel-Eluting Coronary Stent at one year, which will likely guarantee XIENCE’s continued domination of the U.S. stent market.
“It sets a new standard for event-free survival after DES implantation… Whenever we have a patient in the cath lab we want to use the safest stent, and right now the XIENCE V is that stent,” said Gregg Stone, M.D., principle investigator of the SPIRIT IV Trial and co-director of the medical research and education division, and director of Cardiovascular Research and Education at the Center for interventional vascular therapy at NewYork-Presbyterian Hospital/Columbia University Medical Center. “Simultaneous reduction of stent thrombosis, myocardial infarction and target lesion revascularization with XIENCE V demonstrates that low late loss may be achieved with DES without sacrificing safety.”
A year after its introduction, the XIENCE V is the top selling DES in the U.S. market, having about 51 percent of the market share, which includes 27 percent of the share going to Abbott and 24 percent going to Boston Scientific, which markets the XIENCE under the PROMUS brand name. Second quarter 2009 market data shows the remaining market share is divided between TAXUS at 23 percent, CYPHER with 14 percent, and 12 percent for Endeavor. However, that market share will likely tip even more in favor of XIENCE V with the release of the SPIRIT findings.
With 3,690 patients, Dr. Stone said the SPIRIT IV trial is one of the largest randomized clinical trials between two drug-eluting stents. In the trial's primary endpoint, XIENCE demonstrated a statistically significant 38 percent reduction in target lesion failure (TLF) compared to TAXUS (4.2 vs. 6.8 percent). TLF is defined as a composite measure of efficacy and safety outcomes for patients including cardiac death, heart attack attributed to the target vessel myocardial infarction, and ischemia-driven target lesion revascularization (TLR).
The FDA created the new measure to harmonize the definition of major adverse cardiac events across various drug-eluting stent trials. XIENCE also demonstrated a statistically significant 46 percent reduction in TLR compared to TAXUS (2.5 vs. 4.6 percent). TLR is one of the major secondary endpoints of the SPIRIT IV trial. Dr. Stone presented the groundbreaking results Sept. 23 during the 2009 Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco, Calif.
In addition to demonstrating superiority in the primary endpoint of TLF and major secondary endpoint of TLR, XIENCE demonstrated an impressive low rate of stent thrombosis at one year. XIENCE demonstrated an observed 80 percent reduction in stent thrombosis compared to TAXUS (0.17 vs. 0.85 percent) at one year. Per Academic Research Consortium (ARC) definition of definite/probable stent thrombosis, XIENCE demonstrated an observed 74 percent reduction in ARC definite/probable stent thrombosis at one year (0.29 vs. 1.10).
"SPIRIT IV represents one of the largest randomized trials of two drug-eluting stents completed to date. Importantly, this study was performed without routine angiographic follow-up, which may result in a tendency to treat lesions which may not be causing symptoms, and potentially impact results," said Dr. Stone.
"The SPIRIT IV results show that XIENCE V significantly reduces a patient's risk of experiencing a heart attack, the need for a repeat procedure or stent thrombosis." “I think today has really changed the way I plan to take care of patients,” said David Cox, M.D., Lehigh Valley Hospital, who spoke at an Abbott evening session at TCT 2009 following the release of the trial data.
He said the stent’s low profile and flexibility make it easier to deliver and helps reduce imaging and procedure times. He is surprised at the low MACE rate, which he said just a few years ago most cardiologists did not think was possible with a stent. He said TLR is what matters to him and the results of SPIRIT IV show more support for XIENCE over TAXUS Express. Overall patient complications due to either stent was very low, below 7 percent in all categories monitored.
“TAXUS did very well; there were very few patients who had an event,” Dr. Stone said, but added the study results show XIENCE performed better. He also added that the XIENCE V is not without reported complications, as it is prone to edge dissections and has some recoil because it is made out of cobalt-chromium.
Event Rates in Complex Patients
The SPIRIT IV trial included multiple complex patient subgroups, including more than 1,100 patients with diabetes, who typically are sicker and have more challenging artery disease. The SPIRIT III trial data showed TAXUS performed better in diabetics over XIENCE, but it was a small trial and SPIRIT IV was much larger and had many more diabetics.
The TLF rate in SPIRIT IV showed TAXUS had a rate of 6 percent and XIENCE 6.4, which Dr. Stone said is not a statistically significant difference. In nondiabetics, the TLF rates were 3.1 for XIENCE as compared to 6.7 for TAXUS. In the endpoint of ARC definite/probable stent thrombosis, XIENCE demonstrated a 40 percent reduction compared to TAXUS in patients with diabetes (0.80 vs. 1.33 percent), and a 94 percent reduction compared to TAXUS in patients without diabetes (0.06 vs. 1 percent).
XIENCE also demonstrated low event rates in multiple subgroup analyses, such as patients with smaller vessels (reference vessel diameter less than or equal to 2.75 mm), patients with longer lesions (lesion length greater than 13.3 mm) and patients with multivessel disease. In patients with smaller vessels, XIENCE demonstrated a 43 percent reduction in TLF compared to TAXUS at one year (3.9 percent for XIENCE vs. 6.8 percent for TAXUS). In patients with longer lesions, XIENCE demonstrated a 35 percent reduction in TLF compared to TAXUS at one year (4.5 percent for XIENCE vs. 6.9 percent for TAXUS). In patients with two or more lesions treated, XIENCE demonstrated a 49 percent reduction in TLF compared to TAXUS at one year (5.1 percent for XIENCE V vs. 10 percent for TAXUS).
Key Results from the SPIRIT IV Trial:
• A 38 percent reduction in TLF compared to TAXUS (4.2 vs. 6.8 percent).
• A 39 percent reduction in major adverse cardiac events (MACE) compared to TAXUS (4.2 vs. 6.9 percent).
• A 45 percent reduction in TLR compared to TAXUS (2.5 vs. 4.6 percent).
• A 31 percent reduction in cardiac death or target vessel myocardial infarction (MI) compared to TAXUS (2.2 vs. 3.2 percent).
• A 38 percent reduction in heart attacks (MI) attributed to the target vessel compared to TAXUS (1.8 vs. 2.9 percent).
• Comparable rates in cardiac death compared to TAXUS (0.4 vs. 0.4 percent).
• An observed 80 percent reduction in stent thrombosis per protocol definition compared to TAXUS (0.17 vs. 0.85 percent).
• An observed 73 percent reduction in stent thrombosis per ARC definition of definite/probable stent thrombosis compared to TAXUS (0.29 vs. 1.10 percent).
• No statistical difference between XIENCE and TAXUS when treating diabetic patients.
"In SPIRIT IV, XIENCE V demonstrated superiority to TAXUS in the clinically driven endpoint of target lesion failure, which links the results more closely to real-world practice," said Charles A. Simonton, M.D., FACC, FSCAI, vice president, medical affairs, and chief medical officer, Abbott Vascular. "The SPIRIT IV results confirm the consistent and outstanding performance of the XIENCE V stent. We believe these results have the potential to be practice-changing based on the strength of the data."
The Next Big Trial
Boston Scientific funded the SYNTAX study to determine the effectiveness of TAXUS vs. coronary artery bypass grafting (CABG), which showed bypass surgery has a slight performance lead over stenting. Dr. Simonton said Abbott now plans to conduct a similar study.
“We are taking the baton from Boston Scientific, and we will compare XIENCE vs. coronary artery bypass grafts,” he said. The study, named EXCEL, will include 4,200 patients evenly divided between XIENCE Prime stents and CABG. “This will write the guidelines for the rest of our lifetimes,” Dr. Stone said. “We are very, very excited about this, and it will be the focus of our research for several years to come.”
UPDATED INFORMATION: The EXCEL Trial data was presented in October 2017 at TCT. It showed that PCI with second-generation DES (Xience) is noninferior to CABG for clinical outcomes at 3 years following revascularization of unprotected left main lesions.
Read the article "Stents Have Equal Outcomes to Bypass Surgery in EXCEL Trial."
Watch the VIDEO: Stents, Bypass Surgery Have Equal Outcomes in EXCEL Trial — Interview with David Kandzari, M.D.
For more information: www.xiencev.com
1. Gregg W. Stone, Ali Rizvi, William Newman, et al. Everolimus-Eluting versus Paclitaxel-Eluting Stents in Coronary Artery Disease. N Engl J Med 2010; 362:1663-1674. May 6, 2010. DOI: 10.1056/NEJMoa0910496.
2. Gregg W. Stone, Joseph F. Sabik, Patrick W. Serruys, et al. Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease. N Engl J Med 2016; 375:2223-2235. December 8, 2016. DOI: 10.1056/NEJMoa1610227.