Edwards Sapien 3 TAVR System Improves 30-Day Outcomes for Major Endpoints

March 15, 2015—The American College of Cardiology (ACC) announced that data presented at the ACC’s 64th annual scientific session in San Diego, California, showed that treatment with the Sapien 3 transcatheter aortic valve replacement (TAVR) system (Edwards Lifesciences) resulted in lower death, stroke, and paravalvular leak rates than earlier-generation devices in patients at high risk for surgery and showed encouraging results in intermediate-risk patients. 

The Edwards-sponsored trial, PARTNER II S3, evaluated 30-day outcomes with the Sapien 3 valve, the latest modification of the balloon-expandable system used in these procedures. In addition to the study’s 583 high-risk or inoperable patients, 1,076 intermediate-risk patients were treated with the new device. This is the first presentation of large-scale data for the third-generation device and the first report of outcomes in intermediate-risk patients in the United States, noted the ACC.

As summarized by the ACC, the death rate was 2.2%, or 13 patients, in the high-risk group and 1.1%, or 12 deaths, in the intermediate-risk group. Heart-related deaths accounted for 1.4% of the mortality in the high-risk group and 0.9% in the intermediate-risk group. High-risk patients had a stroke rate of 1.5%, 0.9% of them disabling; in the intermediate-risk group, those rates were 2.6% and 1%, respectively.
 
Susheel Kodali, MD, serves as Coprincipal Investigator of the trial. Dr. Kodali is Director of the Heart Valve Center at Columbia University Medical Center/New York-Presbyterian Hospital in New York, New York.

In the ACC press release, Dr. Kodali commented, “The 30-day mortality rates were extremely low, stroke rates were approximately 1% in both groups, and significant paravalvular regurgitation was rare. Death and stroke rates have been decreasing with every modification of the Sapien system.” 

The ACC also noted that major vascular complications occurred in about 5% of high- and intermediate-risk patients, a reduction of two-thirds compared with the first-generation Sapien system. Other clinical events also were reduced from results in previous Sapien studies, including heart attacks in 0.5% of patients, injury to the aortic area (ie, annular rupture) in 0.3%, and coronary obstruction in 0.3%. A new permanent pacemaker was implanted in 13% of high-risk patients and 10% of intermediate-risk patients, a slightly higher rate than with earlier balloon-expandable valves. 

The third-generation Sapien model used in this study was modified with an outer skirt designed to reduce paravalvular leak, which had been associated with poorer outcomes after TAVR, by sealing gaps around the valve. With the new device, 3.7% of patients had moderate leak, and 0.1% had severe leak. By comparison, currently approved devices have rates of moderate or severe paravalvular leak in the range of 10% to 20%. 

Other alterations allow the valve to be delivered with a smaller catheter, increasing the percentage of procedures that can be performed via the femoral artery. Dr. Kodali commented, “For the first Sapien devices, we were able to use the less invasive transfemoral approach in about 60% of patients. For Sapien 3, more than 90% of procedures can be transfemoral.” 

As noted in the ACC announcement, 1-year data for high-risk patients with the new Sapien 3 device will be available later in 2015. Longer-term outcomes for the intermediate-risk patients treated with the new device will be compared with the intermediate-risk surgical patients in the PARTNER IIA trial when the 2-year endpoint is reached. Patients will be followed for 5 years. 

“We needed to see if we’ve solved the valve leakage issue before we move to lower-risk patients. Although we have to wait for longer-term data, what we’ve seen thus far makes us excited about those data and what they’ll show,” concluded Dr. Kodali, who emphasized that these are 30-day data and that longer-term follow up is required. 

In a press release from Edwards Lifesciences, Dr. Kodali stated, “These results of more than 1,600 patients treated with the Sapien 3 valve demonstrate the most significant progress in the development of TAVR and the Sapien family of valves since the first PARTNER study was initiated in 2007.” 

Dr. Kodali continued in the Edwards announcement, “With average ages in the 80s, the high-risk and intermediate-risk patients in the study had strikingly low mortality rates of 2.2% and 1.1%, respectively, despite predicted 30-day mortality that was much higher. Additionally, the rates of significant paravalvular leaks were low in both cohorts—3% for high-risk and 4.2% for intermediate—which represented meaningful improvements over prior studies with earlier generation devices.”

Edwards Lifesciences advised that it continues to plan for United States regulatory approval and launch of SAPIEN 3 early in 2016. The Sapien 3 valve was approved in Europe in January 2014 for the treatment of high-risk and inoperable patients with severe aortic stenosis. It is not approved for the treatment of intermediate-risk patients in Europe. The valve is an investigational device that is not yet commercially available in the United States.