The 1-year follow-up analysis of the doubly randomized SOLVE-TAVI trial uncovered no reason, necessarily, to prefer either of two recent-generation valve prostheses for transcatheter aortic-valve replacement (TAVR or TAVI) over the other in patients at high to intermediate surgical risk.
No significant difference in the composite primary endpoint, the only outcome for which the trial was sufficiently powered, was seen between the Corevalve Evolut R (Medtronic), a self-expandable valve (SEV), and the Sapien 3 (Edwards Lifesciences), a balloon-expandable valve (BEV), at 12 months, consistent with and extending the previously published SOLVE-TAVI 30-day results.
In a separate randomization, the 447-patient trial also showed no important differences in 1-year clinical outcomes between patients who received TAVR while under general anesthesia or those who underwent local anesthesia with conscious sedation, similar to the results at 30 days.
With parity between the two anesthesia approaches probably supporting a preference for the latter, the finding may accelerate the field’s transition to performing TAVR with the patient under conscious sedation in the overwhelming majority of cases, observers said.
The trial raised a few red flags, including a stroke rate that was increased seven times for patients who received the balloon-expandable Sapien 3 valve compared to the SEV. The researchers and expert observers didn’t see the difference as necessarily “real,” attributing it rather to the study’s weak statistical power for such endpoints, unidentified baseline confounders, and the trialists’ acknowledgment that operator experience in the seven-center study was tilted heavily in favor of the Medtronic SEV.
Also, the difference in strokes appeared concentrated in the early weeks after the TAVR procedures, as shown in a post hoc landmark analysis that found no significant difference in stroke rate between the two valves starting at day 30, observed Hans-Josef Feistritzer, MD, PhD, Heart Center at University of Leipzig, Germany, when presenting the 1-year analysis at TCT Connect, the virtual edition of Transcatheter Cardiovascular Therapeutics (TCT) 2020.
The hazard ratio (HR) for the primary endpoint of all-cause mortality, stroke, moderate to severe paravalvular leakage, or permanent pacemaker implantation for Sapien 3 vs Evolut R was 0.95 (95% CI, 0.71 – 1.28; P = .76), with 219 patients in each group.
However, the stroke rates were 6.9% and 1%, respectively, for an HR 7.13 (1.62 – 31.32; P = .002), Feistritzer reported.
“My concern here is that the study sample size is small. It’s just a little over 200 patients in each arm, and that sort of lends itself to random events,” said Susheel K. Kodali, MD, Columbia University Irving Medical Center and New York–Presbyterian Hospital, speaking at a media briefing on the trial held during TCT Connect.
Stroke rates in registry studies and clinical trials of these TAVR valves that have had many more patients have been much lower, said Kodali, who was not associated with SOLVE-TAVI. That “means there’s something we’re missing.”
Feistritzer agreed. “A possible explanation for this finding might be more severe aortic root calcifications in the group receiving the balloon-expanded valve,” he said. “Of course, we need more post hoc analysis, which are already planned, to analyze possible confounders.”
A trial of this size “is vastly underpowered to detect small differences in stroke, let alone large differences,” said TCT Connect course director Gregg W. Stone, MD, Mount Sinai Heart Health System, New York City, after Feistritzer presented the study to attendees. The difference might also be related to the greater operator experience with Evolut R and other Corevalve devices, he proposed.
“I can say pretty confidently that there’s not a seven-fold difference in stroke rates between these two devices. I’m willing to take that one to the bank,” Stone said. To understand whether there is a small difference in stroke rate, “you would need very, large randomized trials with neurologic evaluation.”
The study’s conclusions on anesthesia strategy appear more airtight. SOLVE-TAVI shows “that local anesthesia with conscious sedation could be safely performed in the majority of patients. That’s the clear message,” Feistritzer told theheart.org | Medscape Cardiology. “The hospital stay is shorter, the stay at the ICU is shorter.” Although a cost-benefit analysis is pending, he said, it’s likely that more routine conscious sedation in TAVR would save money, among other gains.
“I really commend them for doing a randomized control trial for this, because there’s been a lot, in the literature, of single-center experience with conscious sedation,” Chad Rammohan, MD, Sutter Health and El Camino Hospital, Mountain View, California, said from the panel at the media briefing. “I’ve converted completely to conscious sedation,” and the registries are showing that it’s now used in 60% to 70% of TAVR cases, he said.
“This is now randomized, controlled trial data showing it’s very safe. The trends are actually improved outcomes, and there’s no price to pay for leaving general anesthesia,” Rammohan said. “I think it’s going to move the country even further and world further to conscious sedation.”
All-cause mortality at 1 year was 19.4% for general anesthesia and 15.2% for conscious sedation, for a cause-specific HR of 1.31 (0.81 – 2.13; P = .27). The rates of cardiovascular death were 1.4% and 0.9%; for stroke, 4.9% and 3.0%; for MI, 0.5% and 1.0%; and for acute kidney injury, 11.7% and 12.2%, respectively. None of the differences was close to significant.
“Maybe I’ll switch over to the local vs the general anesthesia,” offered Vinod H. Thourani, MD, Piedmont Heart Institute, Atlanta, Georgia, a panelist who commented following the formal SOLVE-TAVI presentation. The study doesn’t show an advantage for either general anesthesia or local anesthesia with conscious sedation, he noted, “So I think the general people will say, ‘See, it’s just as good as local.’ And the local people will say it’s just as good as general.”
Feistritzer said conscious sedation is by far preferred in German practice. “Many sites do conscious sedation with a local anesthesia in up to 90% to 100% of TAVI patients. But it’s important to show in a randomized trial that the strategy is safe.”
At the media briefing, Kodali said that at his center, most TAVRs are performed with conscious sedation, “but I still think there’s a role” for general anesthesia in the procedure. The risks of TAVR are independent of the risks from general anesthesia, suggesting usefulness in selected patients, he said.
For example, “If I have a younger guy with a bicuspid aortic valve with heavy calcium, the risk of anesthesia is low, and my risk of getting a poor result with TAVR is higher,” Kodali said. He would use transesophageal echocardiography to guide the procedure because the risk from the accompanying general anesthesia would be low.
TCT Connect is sponsored and run by the Cardiology Research Foundation, which, it frequently noted on the meeting site during the conference, “gratefully acknowledges the educational grant support from ‘Major Benefactors’ Abbott, Boston Scientific, Edwards, and Medtronic,” among other companies. SOLVE-TAVI was supported by the German Heart Research Foundation and the Leipzig Heart Institute. Feistritzer has disclosed no relevant financial relationships. Kodali discloses owning equity in or stock options for Admedus, Dura Biotech, Thubrikar Aortic Valve, MicroInterventional Devices, and Supira; serving on a speakers bureau, consulting, or receiving honoraria from Meril Lifesciences, JenaValve, and Admedus; and receiving grant support or research contracts for Edwards Lifesciences, Abbott Vascular, Medtronic; Boston Scientific, and St. Jude Medical. Stone discloses serving on a speakers bureau, consulting, or receiving honoraria from Cook Medical, Valfix, TherOx, Robocath, HeartFlow, W.L. Gore & Associates, Ablative Solutions, Miracor, Neovasc, Abiomed, Ancora, Vectorious, and Cardiomech; and owning equity in or stock options for Valfix, Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, Biostar funds, SpectraWave, Orchestra Biomed, Aria, and Cardiac Success. Rammohan discloses serving on a speakers bureau, consulting, or receiving honoraria from Abbott Vascular and Medtronic. Thourani discloses receiving grant support or research contracts for Abbott Vascular, Edwards Lifesciences, Boston Scientific, and W.L. Gore & Associates.
Transcatheter Cardiovascular Therapeutics (TCT) 2020: Late-Breaking Clinical Science Session III. SOLVE-TAVI: One-year Outcomes of a Factorial Randomized Trial of Self-expandable Versus Balloon-Expandable TAVR and General Versus Local Anesthesia. Presented October 16, 2020.