Equivalent Mortality at 30 Days and 1 Year With TAVR vs Surgery, Says Large Meta-analysis
Patients with severe aortic stenosis treated with transcatheter aortic valve replacement have early and midterm clinical outcomes equivalent to those who receive the more invasive surgical approach, according to the results of a large meta-analysis.
Data from five clinical trials, including the landmark PARTNER and CoreValve studies, and more than 30 observational studies showed that TAVR results in similar mortality at 30 days and 1 year when compared with surgical aortic valve replacement (SAVR).
“There were two main clinical questions that still had not been answered,” senior investigator Giovanni Esposito, MD (Federico II University of Naples, Italy), told TCTMD. “The first is whether TAVI is similar to surgical valve replacement in patients at high risk or if it’s better now. The second question is whether the introduction of TAVI is justified for patients who are at lower surgical risk. Now, with the data coming out, it looks like these types of patients could also treated with nonsurgical approach.”
The meta-analysis, being published today in the Annals of Internal Medicine, attempts to address both clinical questions, including the highly topical question of performing TAVR in a lower-risk population. In an analysis restricted to low-to-intermediate risk patients, including studies such as the PARTNER 2a study, investigators observed a trend toward lower all-cause mortality at 30 days and 1 year with TAVR, although the results did not achieve statistical significance.
In addition to the PARTNER studies, the meta-analysis included the US CoreValve study, NOTION, and STACCATO. The NOTION study included 280 lower-risk patients with aortic stenosis, while STACCATO, a study comparing the transapical approach against SAVR, was stopped early due to an increased risk of adverse events. In addition to these five randomized controlled trials, the analysis included 31 observational studies comparing TAVR versus surgery in matched patients. In total, 16,638 patients were studied.
With similar rates of all-cause mortality at 30 days and 1 year, the researchers stratified patients by TAVR approach. “We wanted to point out whether a different strategy could influence the outcomes,” said Esposito. “In fact, we found that in the randomized trials, transfemoral TAVI was found to be superior to the surgical approach.”
In four randomized controlled trials, which included 3,063 patients, transfemoral TAVR was associated with a significant 32% reduction in all-cause mortality at 30 days compared with SAVR. This reduction was not observed in patients treated with the transapical approach. At 1 year, transfemoral TAVR was associated with a significant 20% in all-cause death versus SAVR.
Speculating on the future of TAVR, Esposito said he is confident the procedure will gain traction in the low-to-intermediate risk patients, particularly since there is evidence of benefit—a trend in their meta-analysis—in lower-risk patients treated with first-generation devices. That said, he stressed long-term data are needed, particularly on the durability of the valve. At the end of the day, the choice between TAVR and SAVR should be individualized, he said.
Ted Feldman, MD (NorthShore University HealthSystem, Evanston, IL), who was not involved in the analysis, urged that the reduction in all-cause mortality in the low-to-intermediate-risk patients should be interpreted cautiously. NOTION, said Feldman, is the lone “low-risk” clinical trial in the analysis and just 139 patients were randomized to TAVR in that study. As a result of such small numbers, it is impossible to make definitive conclusions about benefit, he said, noting that nearly all patients analyzed would be considered intermediate risk for surgery.
In January, the US Food and Drug Administration approved the start of PARTNER III, an Edwards Lifesciences-sponsored study of approximately 1,300 elderly patients at low risk for mortality were they to undergo surgical valve replacement (STS score < 4). Medtronic is also conducting a study that will include approximately 1,200 low-risk patients with severe aortic stenosis randomized to TAVR with the CoreValve Evolut R system or SAVR. Patients randomized in the trial will be considered low risk for surgery if they have a less than 3% risk of death from valve-replacement surgery.
In the meta-analysis, which was led by Giuseppe Gargiulo, MD (Federico II University of Naples, Italy), there was a statistically significant reduction in early MI (≤ 30 days), major bleeding, and acute kidney injury with TAVR, as well as a significant 76% reduction in the risk of new-onset atrial fibrillation. Going in the other direction, TAVR was associated with significant two-fold higher risk of early pacemaker implantation, a four-fold higher risk of vascular complications, and a more than six-fold higher risk of paravalvular leak compared with surgery.
To TCTMD, Esposito said that given that most patients were treated with first-generation Sapien and CoreValve devices, the risk of early adverse events, including the risk of paravalvular leak, should decline with newer iterations. For example, vascular complications would be expected to decline with the use of smaller sheaths and improved procedural techniques. He added that newer systems will enhance the ability of physicians to more accurately place the valve, which will hopefully translate into a reduction in the need for a permanent pacemaker.
“The technical skills of the operator are improving, as are the technical properties of the systems,” said Esposito.
Gargiulo told TCTMD the US and European recommendations for TAVR in high-risk patients should strengthened and also extended to patients at intermediate risk for surgery. In high-risk patients, TAVR is awarded a IIa (level of evidence B) recommendation from the European Society of Cardiology, while the American Heart Association/American College of Cardiology recommend TAVR as a reasonable alternative to SAVR in patients with severe aortic stenosis who are at high risk for surgery (class IIa, level of evidence B).
On the whole, Feldman said he is unsurprised by the findings, noting the data from the randomized, controlled trials, as well as data from registries, continue to show strong support for TAVR in the treatment of aortic stenosis. He noted the meta-analysis is published in a journal focusing on the general internal medicine community, who might not be aware of how far TAVR has come since the first implantation in 2002.
“In the field, we know that all the studies are moving concordantly,” said Feldman. “One study might show something a little different, but the really big points [in the meta-analysis] are consistent.”
Feldman added that the observed reduction in new-onset atrial fibrillation is impressive, calling it one of the “underappreciated bad actors” following cardiac surgery.
- TAVR With Sapien XT Noninferior to Surgery in Intermediate-Risk Patients, With a Win For Transfemoral
- OBSERVANT: Similar Safety After TAVR, Surgery in Lower-Risk ‘Real-World’ Patients
- NOTION: 2-Year Data Show Positive Outlook for TAVR in Lower-Risk Patients
Gargiulo G, Sannino A, Capodanno D, et al. Transcatheter aortic valve implantation versus surgical aortic valve replacement. Ann Intern Med. 2016;Epub ahead of print.
- Esposito reports no conflicts of interest. Gargiulo reports grants from the CardioPath PhD program at the Federico II University of Naples and from the European Association of Percutaneous Coronary Interventions.
- Feldman reports receiving consulting fees and grants from Abbott Vascular, Boston Scientific, and Edwards Lifesciences.