“No Surprises” in 5-Year PARTNER I Data Presented at ACC

March 15, 2015—The American College of Cardiology (ACC) announced that 5-year data from the PARTNER I clinical trial demonstrated that the Sapien transcatheter heart valve (Edwards Lifesciences) is a feasible option for patients with severe aortic stenosis deemed to be at high risk for open heart surgery; however, valve leakage was more common with the first-generation valve evaluated in this study than with surgery. 

The PARTNER I data was presented at the ACC’s 64th annual scientific session in San Diego, California. The study was simultaneously published online in The Lancet. 

The PARTNER I trial randomly assigned 699 high-risk patients to either standard surgery or transcatheter aortic valve replacement (TAVR) with the Sapien device, which is approved by the US Food and Drug Administration for use in inoperable and high-risk operable patients.

In the ACC announcement, Michael Mack, MD, commented, “The surprise is that there were no surprises. The findings at 5 years confirm the earlier findings that outcomes are equivalent in high-risk surgical patients with surgery and with TAVR.” Additionally, there were no signs of structural valve deterioration or loss of valve function with TAVR, stated Dr. Mack, who is Chief of Cardiovascular Disease at Baylor Scott and White Health in Dallas, Texas.

As summarized by the ACC, at 5 years, death and stroke rates were statistically the same in both groups: 67.8% of TAVR patients and 62.4% of surgery patients had died, with a median survival of 44.5 months with TAVR and 40.6 months with surgery. Stroke rates were 15.9% for TAVR patients and 14.7% for surgery patients. Rehospitalization rates and functional outcomes also were the same in both groups.

The ACC noted that transcatheter valves have not approached the low leakage rate around the valve that can be achieved by surgery. As in previous findings, the rate of moderate or severe leakage around the valve remained significantly higher for the TAVR group—14% with TAVR and 2.1% with surgery—and at 5 years, that higher leakage rate still led to an increase in deaths, with a 9% greater death rate in patients with leakage than in patients who did not have a significant leak. 

The first-generation Sapien valve used in this trial has already been replaced by a second-generation device that is approved in the United States, and a third-generation valve has been specifically designed to reduce leakage. Thirty-day results for the third-generation valve will be reported separately at the current scientific session, stated the ACC. 

The ACC advised that data analysis identified several indications and cautions for both procedures. Kidney disease was a significant issue with TAVR but not surgery, a high Society of Thoracic Surgeons (STS) risk score was a predictor of death in the surgery group, and liver disease was a significant factor in both groups. 

TAVR patients will be followed annually for life in the STS/ACC Transcatheter Valve Therapies registry, and surgery patients will not be followed beyond 5 years. 

Dr. Mack concluded, “You can look at this trial and say, ‘There’s no difference in the two arms, what’s the big deal?’ But that’s the major message. With a brand-new therapy using a first-generation device that represents most of the experience of the clinical trial sites, outcomes were virtually identical to the standard of care for the last 50 years.” 

In a press release from Edwards Lifesciences, Dr. Mack stated, “It's remarkable that this 5-year data report continues to show equivalency between what was then a brand new procedure with a first-generation TAVR device and the gold standard of surgery, which has been honed over 50 years of experience. Just as we observed in the 5-year report from ThePARTNER trial on outcomes in inoperable patients treated with Sapien, the high-risk patients also had durable valve performance. These data show that TAVR is an effective treatment for these patients.” 

Edwards Lifesciences advised The PARTNER trial enrolled patients in the high-risk surgery cohort (cohort A) between May 2007 and Septemer 2009 and studied 699 patients with severe, symptomatic aortic stenosis deemed at high risk for open heart surgery. Patients were evaluated by a multidisciplinary heart team and randomized to receive either traditional open heart surgery or the Sapien valve via transfemoral or transapical delivery. This trial represented the initial TAVR experience for most trial sites in the nited States, the company noted.

The US Food and Drug Administration approved the Sapien valve in November 2011 for the treatment of inoperable patients and expanded the indication to high-risk surgical patients in October 2012. In June 2014, the agency approved the next-generation Sapien XT valve for the treatment of both inoperable and high-risk patients.