CHICAGO (FRONTLINE MEDICAL NEWS) – Transcatheter aortic-valve replacement performed as well as surgical-valve replacement in patients with an intermediate mortality risk in a prospective, randomized trial with more than 2,000 patients followed for 2 years, the first randomized trial to compare the efficacy and safety of transcatheter aortic-valve replacement against surgical replacement in patients who did not have a high mortality risk.

The results “support TAVR [transcatheter aortic-valve replacement] as an alternative to surgery in intermediate-risk patients similar to those included in this trial,” said Dr. Craig R. Smith at the annual meeting of the American College of Cardiology. The findings from the Placement of Aortic Transcatheter Valves (PARTNER) 2 cohort A trial “will increase use of TAVR,” predicted Dr. Smith, professor and chairman of surgery at New York–Presbyterian Hospital/Columbia University in New York.

Until now, TAVR had been compared with surgical aortic-valve replacement in two prospective, randomized trials that both enrolled either high-risk or inoperable patients with severe aortic stenosis, the PARTNER 1 trial that tested the original Sapien TAVR system, and the U.S. CoreValve High-Risk Study that tested the original CoreValve system (often now called CoreValve classic). The average Society of Thoracic Surgeons (STS) operative risk score of high-risk patients enrolled in PARTNER 1 was 11.8%, and the average risk score in patients enrolled in the CoreValve study was 7.3%. In contrast, the design of PARTNER 2A specified that enrolled patients have a STS risk score of 4%-8%, a criterion actually met by 81% of the enrolled patients, and the average STS risk score of all patients enrolled in PARTNER 2A was 5.8%.

Although U.S. labeling for both the Sapien valve and its later iterations, Sapien XT and S3, and for CoreValve and its later iteration, Evolut R, specify that treated patients should have a STS risk score of at least 8%, the labeling also gives the heart teams that perform TAVR the latitude to treat patients with risk scores below 8% when the heart teams identify other patient factors that confer high risk such as frailty or comorbidities. U.S. and European TAVR registries have documented that many patients with STS risk scores below 8% have undergone TAVR since these systems received regulatory approval. The new results from PARTNER 2A may change that by leading to revised labeling that cuts the STS risk-score threshold.

“These findings might lead to a labeling change that would avoid a lot of the patient-evaluation gymnastics that have been used to justify” TAVR treatment, noted Dr. Smith. New labeling like this “would sanction what is already going on” in terms of which patients undergo TAVR.

Others who heard these results at the meeting agreed they were an important milestone in TAVR development and its expanding use.

The new results “make a huge difference,” commented Dr. David R. Holmes Jr. , an interventional cardiologist and professor at the Mayo Clinic in Rochester, Minn. “We base many of our guidelines on the results from randomized, controlled trials. It’s true that there are reports of lower-risk patients undergoing TAVR, but we now have results from a well-designed trial with well-controlled and adjudicated endpoints that documents the safety and efficacy of TAVR in intermediate-risk patients,” Dr. Holmes said in an interview.

“The results will have a very important influence on the choice between TAVR and surgery,” commented Dr. Duane S. Pinto , an interventional cardiologist at Beth Israel Deaconess Medical Center in Boston. “It validates the strategy” of using TAVR in patients with a risk score of 4%-8%. “TAVR has already been used in these patients, but these results validate this, especially when used in a transfemoral approach,” Dr. Pinto said in an interview.

One aspect of PARTNER 2A that received a lot of discussion at the meeting was whether enrolled patients could appropriately be characterized as “intermediate” in their risk level. Although their average STS risk score of 5.8% fell squarely within the target range specified for the study, they averaged 82 years old, and other clinical features at baseline suggested a higher risk population. The published report of the PARTNER 2A results that appeared online concurrent with Dr. Smith’s report at the meeting ( New Engl J Med 2016;doi:10.1056/NEJMoa1514616 ) acknowledged that STS risk scores of 4%-8% place the enrolled patients into the upper 20% for risk of all U.S. patients who undergo surgical aortic-valve replacement

“I would characterize the enrolled patients as ‘less high risk’ rather than intermediate risk,” said Dr. Pinto.

But as Dr. Smith explained “even if the enrolled patients are not ‘intermediate’ risk they are at a different risk level” than were the patients enrolled in the prior TAVR randomized trials.

In the PARTNER 1 high-risk trial, the overall 1-year rate of all-cause mortality was 24% and 27% in the TAVR and surgical arms of the study, respectively. In the CoreValve trial these rates were 14% with TAVR and 19% with surgery. In PARTNER 2A 1-year all-cause mortality was 12% with TAVR and 13% with surgery.

Two other notable findings of PARTNER 2A were the superior outcomes of patients who underwent TAVR using a transfemoral approach, and the improved outcomes that all TAVR patients had compared with surgical valve replacement for several secondary outcomes.

The rate of the study’s primary outcome, all-cause death or disabling stroke after 2 years, was cut by a relative 21% in the 77% of TAVR patients who underwent a transfemoral procedure, compared with the surgery patients, a difference that was of borderline statistical significance. In contrast, the entire group of TAVR patients, including those treated via nontransfemoral routes, had an 11% relative reduction of the primary endpoint, compared with surgery, a difference that was not statistically significant but did easily meet the study’s prespecified definition of noninferority. Dr. Smith and others were especially encouraged by these findings as PARTNER 2A used the older Sapien XT TAVR system that is not often used today in U.S. practice. When U.S. patients undergo TAVR with a balloon-expandable valve they most often receive treatment with the S3 system, much smaller than XT and hence much more likely to be used with a transfemoral approach.

Other secondary outcomes included life-threatening or disabling bleeding events, which after 2 years had occurred in 17% of the TAVR patients and 47% of those who underwent surgery; atrial fibrillation, which occurred in 11% of the TAVR patients and 27% of those undergoing surgery; and acute kidney injury which occurred in 4% of TAVR patients and 6% of the surgery patients. With 2-year follow-up, the rate of disabling strokes was 6% in both arms of the study.

PARTNER 2A was sponsored by Edwards Lifesciences, the company that markets the Sapien TAVR systems. Dr. Smith has received travel grants from Edwards. Dr. Holmes had no disclosures, Dr. Pinto has been a consultant to Medtronic.

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