Medtronic's CoreValve TAVR System Widens Advantage Over Surgery at 2 Years


March 15, 2015—Two-year data show a continued survival advantage for transcatheter aortic valve replacement (TAVR) with the CoreValve self-expanding device (Medtronic plc) over standard surgery in high-risk patients with severe aortic stenosis, according to research presented at the 64th annual scientific session of the American College of Cardiology (ACC) in San Diego, California. 

Medtronic, the sponsor of the trial, advised that the CoreValve system was approved by the US Food and Drug Administration in 2014 for patients at extreme risk and high risk for surgery. The device received European CE Mark approval in 2007

As summarized in a press release from Medtronic, the CoreValve US Pivotal High Risk trial randomized 747 severe aortic stenosis patients at 45 centers in the United States to treatment with either the CoreValve System or open heart surgery. The patients were estimated to have a predicted risk of operative mortality of 15% or higher at 30 days, assessed by two clinical site surgeons and confirmed by at least two surgeons on a National Screening Committee.

Medtronic noted that the average age of patients in the study was 83.2 years, and the study enrolled an approximately equal number of men and women. Patients had a Society of Thoracic Surgeons Predicted Risk of Mortality estimate of 7.4%. Additionally, these patients had documented comorbidities, frailty, and disability that placed them at increased risk for surgery.

A separate announcement from the ACC stated that mortality rates at 1 year in the trial were significantly lower for the 390 TAVR patients than for the 357 patients who underwent open heart surgery. The 2-year data include an additional three patients, two of whom received a smaller second-generation CoreValve that was not available earlier in the trial..

The study’s Lead Investigator is Michael J. Reardon, MD, who is Professor and Allison Family Chair of Cardiovascular Research at Houston Methodist Hospital in Houston, Texas.

In the ACC press release, Dr. Reardon stated, “Survival is statistically better with TAVR and sustained at 2 years. We found that the survival advantage actually increases for TAVR—that the absolute difference in all-cause death rates between the two groups has widened, with 4.8% more people surviving with TAVR than surgery at 1 year and 6.4% more surviving with TAVR at 2 years.”

In a press release from Medtronic, the company noted this increase in absolute difference in all-cause mortality between the two groups and reported that the rate of all-cause mortality was significantly lower in TAVR patients than in the SAVR patients (22.2% vs 28.6%; P = .04).

As summarized in the ACC announcement, the self-expanding CoreValve device also had significantly lower rates for other endpoints compared with open surgery. The rate of strokes was 10.9% for TAVR patients and 16.6% for surgery patients (P = .05); and 29.7% of TAVR patients had a major adverse cardiovascular or cerebrovascular event compared with 38.6% of surgery patients (P = .01). Results favored TAVR across all subgroups analyzed.

In the company's announcement, Medtronic noted that the major stroke rates were comparable (6.8% vs 9.8%; P = .25) but that the combined endpoint of all-cause mortality or major stroke significantly favored the TAVR group compared to the surgical group (24.2% vs 32.5%; P = .01). Medtronic also noted that although the echocardiographic parameters of effective orifice area and mean aortic valve gradient remained stable for both groups over the 2-year period, the TAVR group showed superior hemodynamics compared with the surgical group time points during the clinical trial follow-up (P ≤ .001).

Dr. Reardon commented in the ACC press release, “Durability is an issue, and we saw no evidence of TAVR valve deterioration. Effective valve orifice and mean pressure gradients (measures of valve quality) were statistically superior with TAVR at every time point during the trial.”

The investigators noted that leaking around the new valve is one area where surgery consistently performs better than TAVR in clinical trials. In the ACC press release, Dr. Reardon explained, “Moderate to severe paravalvular leakage with TAVR was low at 1 year at 6% and stayed low at 2 years at 6.1%.” He noted that, unlike some other TAVR studies, leaks have not had an impact on mortality with this valve. “We had very few cases of moderate or more leaks, and this may be why we don’t see a mortality signal with leakage.” 

The ACC press release advised that with these latest findings, Dr. Reardon sees reason to revisit current guidelines. He concluded, “This trial moves the field forward in that American College of Cardiology/American Heart Association guidelines state that TAVR is a reasonable alternative to surgical valve replacement in high-risk patients, as judged appropriate by the heart team. This trial’s data suggest that TAVR with the self-expanding valve should be the preferred treatment in patients with symptomatic severe aortic stenosis at increased risk from surgery.” 

Acknowledging that these are early findings, Dr. Reardon said that longer follow-up is needed to confirm that this valve continues to demonstrate benefits over surgery. The CoreValve High Risk trial will follow patients for 5 years, noted the ACC.