Survival Benefit of CoreValve in High-Risk Patients Persists at 2 Years
In patients with severe aortic stenosis who are at increased surgical risk, the survival advantage of TAVR using a self-expanding bioprosthesis over surgery seen after 1 year is sustained at 2 years, according to follow-up from the CoreValve US Pivotal Trial published in the July 14, 2015, issue of the Journal of the American College of Cardiology.
“Superior survival, less overall stroke, a superior [MACCE] rate and improved valve hemodynamics are all possible with the self-expanding TAVR system compared with [surgery] and should be considered in patients at increased risk,” say Michael J. Reardon, MD, of the Houston Methodist DeBakey Heart & Vascular Center (Houston, TX), and colleagues.
Still, they caution, moderate-to-severe paravalvular leak is more common with TAVR and should be the target of future efforts to minimize it.
For the CoreValve US Pivotal Trial, investigators randomized 797 patients (mean age 83.2 years; 53% men) with severe aortic stenosis who were at increased surgical risk to TAVR with the CoreValve self-expanding bioprosthesis (Medtronic) or surgical aortic valve replacement at 45 US centers. Most TAVR-treated patients (82.8%) underwent iliofemoral procedures. Within the as-treated cohort, the mean STS Predicted Risk of Mortality score was 7.4, and 86.1% of patients had NYHA class III or IV symptoms.
At 1 year, mortality for the TAVR group was an absolute 4.9% lower than for the surgical arm (P = .04 for superiority).
Mortality Advantage Enhanced at 2 Years
Two-year data—which were initially presented at the 2015 American College of Cardiology/i2 Scientific Session in San Diego, CA—show an absolute reduction of 6.4% in all-cause mortality with TAVR vs surgery in the as-treated cohort and a similar decline in the intention-to-treat cohort. In addition, stroke tended to be lower and MACCE, life-threatening or disabling bleeding, acute kidney injury, and new or worsening A-fib were significantly reduced in the TAVR group. In contrast, rates of major vascular complications, permanent pacemaker implantation, moderate-to-severe regurgitation, and reintervention were higher in the percutaneous group (table 1).
No interactions were seen between treatment and any of 9 subgroups with respect to mortality. In addition, the prevalence of NYHA functional classes I or II was similar between the TAVR group (92.1%) and the surgical group (90.5%).
Early hemodynamic performance was better after TAVR than after surgery (P < .001 for improvements in both mean aortic valve area and gradient), and the difference remained stable over 2 years.
According to the authors, the results “suggest that self-expanding transcatheter valve therapy should be considered standard of care and preferred over surgery in this patient population.”
TAVR’s Superiority Gains Credibility
In an accompanying editorial, Ron Waksman, MD, and Augusto D. Pichard, MD, of the MedStar Washington Hospital Center (Washington, DC), note that randomized trials involving high-risk patients have already proven TAVR—with either a balloon-expandable or self-expanding valve—to be noninferior to surgery, while data showing superiority of the latter technology had met with some skepticism. However, they add, “the reduction in overall mortality, which was of uncertain significance in the 1-year data, is now confirmed” at 2 years.
Still, the editorialists say, the current study raises several questions:
- What is the mechanism for the superiority of the self-expanding valve with regard to mortality and for the improvement between the first and second years?
- Are these results consistent regardless of the access site (eg, transfemoral vs transaortic)?
- Are the outcomes generalizable to other prostheses or specific to the CoreValve self-expanding device?
With regard to the first issue, the study authors suggest that higher rates of serious bleeding, transfusion, and acute kidney injury at the time of surgery; worse long-term valve performance; and more episodes of A-fib may explain lower survival in surgical patients.
Drs. Waksman and Pichard counter that these arguments are “not entirely supported by published reports.” Adding to the mystery, they say, is the fact that moderate-to-severe regurgitation—an established predictor of post-TAVR mortality—did not seem to influence the outcome in that group.
In a telephone interview, Ted Feldman, MD, of Evanston Hospital (Evanston, IL), told TCTMD that there is “a laundry list” of factors associated with each therapy that might contribute to mortality, and for surgery this includes not only increases in transfusion and A-fib but also more patient-prosthesis mismatch. “What we’re seeing in these CoreValve 2-year results is that on balance these factors weigh more heavily on surgery,” he commented.
Likely a Class Effect
In addition, Dr. Feldman dismissed any possible inference from the different survival rates between the CoreValve and PARTNER trials that the self-expanding device might hold an edge over the balloon-expandable Sapien valve (Edwards Lifesciences).
“The CoreValve trial was done several years after PARTNER, and the single thing that has changed most over that time is the use of CT scans for patient assessment and valve sizing,” he said. “That has had a dramatic impact on everybody’s results.”
The editorialists note that surgery was superior to transapical TAVR for early mortality and quality of life in PARTNER IA, and because about 17% of percutaneous cases in the CoreValve trial were not performed via the iliofemoral route, “the statements of superiority should be carefully reviewed for the TAVR alternative access.”
But Dr. Feldman pointed to the overall evolution of TAVR technology toward lower-profile devices. Globally, the transfemoral approach is now employed in 80% to 90% of all procedures, he reported.
As to questions about the durability of percutaneous prostheses, Dr. Feldman cited reassuring 5-year data from PARTNER. Even if TAVR valves did turn out to have a shorter life than surgical prostheses, “we can still do valve-in-valve pretty easily, so we get several chances to extend the life of TAVR devices,” he added.
Guidelines Should Be Updated
Despite their caveats, Drs. Waksman and Pichard conclude: “Looking forward, the message is clear: TAVR via femoral access should be considered as the first-line therapy for patients with [severe aortic stenosis] who are at increased risk for surgery.
“With the rapid accumulation of data, it is time for the societies to update and upgrade their guidelines and equate them to the surgery guidelines for the high-risk population,” they continue, adding that insurers should also recognize “the totality of the evidence that supports TAVR” and bring reimbursement in line with FDA labeling.
Dr. Feldman agreed, saying, “Now that we have 2 randomized trials [with good outcomes], it’s just a question of when we’re going to get a class I guideline indication for high-risk patients.”
1. Reardon MJ, Adams DH, Kleiman NS, et al. 2-year outcomes in patients undergoing surgical or self-expanding transcatheter aortic valve replacement. J Am Coll Cardiol. 2015;66:113-121.
2. Waksman R, Pichard AD. Will TAVR become the default treatment for patients with severe aortic stenosis [editorial]? J Am Coll Cardiol. 2015;66:122-124.
- The study was sponsored by Medtronic.
- Dr. Reardon reports serving on the medical advisory board for Medtronic.
- Dr. Waksman reports receiving personal fees from Abbott Vascular, Biotronik, and Medtronic; grants and personal fees from AstraZeneca, Biosensors International, and Boston Scientific; and grants from Edwards Lifesciences and The Medicines Company.
- Dr. Pichard reports no relevant conflicts of interest.
- Dr. Feldman reports receiving consulting fees and grants from Abbott Vascular, Boston Scientific, and Edwards Lifesciences.