Conference Coverage
“We don’t demand that for iterations of surgical valves,” agreed Dr. Kodali.
CoreValve looks good longer-term
While SAPIEN 3’s performance turned heads, 2-year results from the CoreValve’s pivotal trial reported at the meeting further deepened the impression that TAVR offered substantial advantages, compared with surgical aortic valve replacement in high-risk patients. The 2-year outcomes followed the trial’s primary endpoint reported last year, the 1-year results, which had shown a statistically significant advantage in survival, compared with surgery (N. Engl. J. Med. 2014;370:1790-8).
Mitchel L. Zoler/Frontline Medical News
Dr. Michael Reardon
The 2-year follow-up showed this advantage was “sustainable, durable, and widening,” reported Dr. Michael Reardon, professor of cardiothoracic surgery at the Methodist Hospital in Houston.
For example, 2-year all-cause mortality stood at 29% in patients who underwent surgical valve replacement and 22% in those who received TAVR with CoreValve, a statistically significant widening of the between-group gap, compared with the respective 19% and 14% mortality rates after 1 year. The rate of all-cause death or major stroke after 2 years ran 33% and 24% with surgical valve replacement or TAVR, respectively, compared with rates of 23% and 16% after 1 year.
Concern about excess strokes with TAVR, “one of our early worries, seems to have been put to bed,” Dr. Reardon said. The results also showed CoreValve substantially surpassed open surgery for valvular blood flow metrics across the full range of follow-up time points.
Several factors might have produced the widening outcomes between years 1 and 2 following a different one-time intervention, Dr. Reardon said, such as significant differences in the incident rate following intervention for disabling or life-threatening bleeding, atrial fibrillation, and acute kidney injury. All three complications occurred significantly more often in the surgery patients, compared with those treated with TAVR, and while the bulk of the difference in incidence showed up within the first month after intervention, each of these complications could have important long-term effects on survival and stroke rates, Dr. Reardon explained. On the other side of the ledger, open surgery when compared with CoreValve resulted in significantly fewer acute and long-term episodes of vascular complications and fewer new pacemakers, but these complications likely have less impact on stroke and mortality than the three that occur more often with surgery.
Overall, the widening gap in outcomes between surgery and TAVR “suggests that TAVR with a self-expanding valve [CoreValve] should be considered the preferred treatment,” compared with surgery in high-risk patients, Dr. Reardon said during his presentation at the meeting, a similar conclusion to what Dr. Kodali said about SAPIEN 3.
“These results really do move the needle forward,” said Dr. Popma, a CoreValve trial coinvestigator. “We see for the first time that [TAVR] may indeed be superior, and although durability remains a long-term question we have 2-year data that CoreValve has held up.”
First-generation SAPIEN TAVR shows 5-year stability
The third piece of the TAVR trilogy reported at the meeting was 5-year follow-up results from the first U.S. TAVR pivotal trial (PARTNER 1) using the first-generation SAPIEN device, which is no longer available in the United States. Those results from patients treated during 2007-2009 showed continuation of the statistical overlap between surgical valve replacement and SAPIEN TAVR for all-cause mortality, stroke, and other outcomes (Lancet 2015 [doi:10.1016/S0140-6736(15)60290-2]). Importantly, the results also showed no suggestions of deteriorating function in the TAVR valve after 5 years, reported Dr. Michael J. Mack at the meeting.
©Nick Piegari/Frontline Medical News
Dr. Michael Mack
“It’s very encouraging, but we’d all like to go out to 10-12 years, and then we’d feel a lot better about it,” commented Dr. Reardon, who did not participate in the PARTNER trial. But given 5 years of apparently reliable function from a TAVR valve, the issue of long-term durability of these valves, an open question at the start of the SAPIEN trial, may be now coming to resolution, he suggested, at least for octogenarians, who are emerging as the prime demographic for TAVR.
“Tissue valves we place surgically deteriorate at different rates depending on a patient’s age when you put them in. In 30-year-olds many valves deteriorate after 10 years; in 50-year-olds maybe 15% will deteriorate, and in 70-year-olds almost none,” Dr. Reardon explained. “No one knows why.” Because many TAVR patients are at least 80 years old “it may take 10 years to see a signal of deterioration, or we might never see a signal,” he said.
SAPIEN versus CoreValve?
Although SAPIEN 3 may be on the U.S. market within the next year, for the time being routine U.S. TAVR practice is limited to two options, approved for high-risk or inoperable patients but not patients at intermediate risk: the CoreValve, which has now clearly bested surgery for all major endpoints over at least the midterm, and the SAPIEN XT model, the second-generation SAPIEN TAVR system that sits between the first generation and SAPIEN 3 and showed documented performance that roughly tracked with the original SAPIEN model. When approving the SAPIEN XT for U.S. marketing in June 2014 for operable high-risk patients as well as inoperable patients, the agency said the evidence indicated that XT was “noninferior” to SAPIEN in high-risk patients.
