Meeting News

Intermediate-risk trials offer hope for TAVR in low-risk patients

SAN DIEGO — Results from trials of transcatheter aortic valve replacement in patients at intermediate surgical risk suggest that the procedure would also be reasonable for low-risk patients, an expert said at the Society for Cardiovascular Angiography and Interventions Scientific Sessions.

“There are growing TAVR indications, and the volume in our cath labs are increasing, which is driven by the clinical trials that have established what these indications are,” said Steven J. Yakubov, MD, FACC, FSCAI, John H. McConnell Chair of Advanced Structural Heart Disease; system chief of OhioHealth Structural Heart Disease; and medical director of OhioHealth Research Institute.

Intermediate-risk trials

Clinical outcomes after TAVR appear to be similar to those with surgical AVR in intermediate-risk patients, according to Yakubov.

For instance, SURTAVI showed that there were no differences in mortality or disabling stroke with TAVR using the CoreValve System (Medtronic) vs. surgical AVR in an intermediate-risk patient population. Additionally, NYHA functional class improved from class III to class I in about 70% of patients.

A closer look at 30-day clinical outcomes also indicated no significant differences between the two treatment groups in mortality, stroke and major bleeding. There were more blood transfusions, kidney injury and atrial fibrillation in the surgical AVR group, and more pacemaker implantation in the TAVR group, which were roughly comparable outcomes, he noted.

Yakubov also discussed the NOTION trial. The study’s patients had a Society of Thoracic Surgeons risk score of about 2.9%, although most patients would have been classified as intermediate risk, he said.

Similar to SURTAVI, all-cause mortality was similar between patients who underwent TAVR and those who underwent surgical AVR. Further, the effective orifice area and the gradients that were achieved with TAVR in the intermediate-risk group are comparable to what has been seen in the high-risk and extreme-risk patient populations.

“These gradients and the effective orifice area are higher in TAVR than they are with surgical AVR, and they appear to be durable,” Yakubov said. “We’re not seeing any degradation in the effective orifice area or an increase in gradients out to 5 years. ... What we’re seeing clinically is truly TAVR valve durability.”

Potential issues

Although the data are promising, Yakubov said trials of TAVR in low-risk patients, including the Medtronic TAVR Low-Risk Trial and PARTNER 3, tend to exclude bicuspid valve disease. Therefore, the effects of TAVR in these patients will likely only be answered using registry data, he said.

Another concern with low-risk patients is the issue of reduced leaflet valve motion. There is often normalization with anticoagulation, he said, and it can occur across every transcatheter valve as well as in surgical valves.

Paravalvular leak also remains a problem in low-risk patients. Industry, however, has come to the aid of interventional cardiologists by developing better valves, Yakubov said. For example, usually only mild paravalvular leak is seen with the Sapien 3 valve (Edwards Lifesciences). Additionally, the Evolut PRO valve (Medtronic), which has a pericardial wrap on the inner and outer surface at the bottom of the valve, was associated with significant reductions in paravalvular leak in its clinical trial.

Unfortunately, TAVR is still linked to higher rates of pacemaker implantation compared with surgical AVR, but many single-center studies are showing rates in the 5% range, which is closer to what is observed with surgery, Yakubov noted. Although this rate remains higher with the CoreValve valve (Medtronic), he said it is possible to achieve pacemaker rates of 10% with the device.

Current data

Data on TAVR in low-risk populations can be derived from trials already conducted in intermediate-risk patients as well as initial information from low-risk trials, according to Yakubov.

For instance, in SURTAVI, a number of patients had STS scores lower than 4% but were considered to be intermediate risk according to the surgeon. Among patients with lower STS scores, he noted, there was a signal that mortality and stroke outcomes were not worse with TAVR than they were with surgery and may even be slightly better. Similarly, in the NOTION trial in which all patients had STS scores lower than 4%, there was no signal of worsening mortality, stroke or MI in the TAVR arm compared with the surgical AVR arm, and valve durability also appeared to be “excellent,” Yakubov noted.

Early data from the first 125 patients in the Medtronic TAVR Low Risk trial are also promising. In the trial, the patients are matched 1:1 using propensity matching from the STS database. Of these first 125 patients, 80% had conscious sedation, 87% received Sapien 3 valves and 13% received CoreValve valves.

The primary outcome of mortality was 0% at 30 days. The rates of stroke and MI were also 0%. Only one patient had coronary obstruction, which did not result in a significant clinical event, according to Yakubov. Additionally, he noted that the pacemaker implantation rate was 4%, NYHA functional class improved, hemodynamics were good, paravalvular leak was low and other adverse events compared favorably to what has been observed in the intermediate-risk patient population.

“The intermediate-risk trials give us hope that the low-risk trials will provide excellent outcomes,” Yakubov said. “The TAVR issues of old — paravalvular leak, pacemaker rates, stroke, valve durability — are either improving or going away. However, we do need to address and know more about leaflet thrombosis, such as who should be anticoagulated and who is at risk, and then the clinical indications, hopefully from low-risk studies, should drive further growth in this field.” – by Melissa Foster

Reference:

Yakubov SJ. TAVR Academy III: Unresolved Issues and Future Directions. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; April 25-28, 2018; San Diego.

Disclosure: Yakubov reports he serves on the medical advisory board for Abbott Vascular, Boston Scientific and Medtronic; he is a steering committee member/proctor for Medtronic; he serves on the advisory board for and has equity interest in BioStar Ventures; and he is a consultant for Foldax and SentreHeart.

SAN DIEGO — Results from trials of transcatheter aortic valve replacement in patients at intermediate surgical risk suggest that the procedure would also be reasonable for low-risk patients, an expert said at the Society for Cardiovascular Angiography and Interventions Scientific Sessions.

“There are growing TAVR indications, and the volume in our cath labs are increasing, which is driven by the clinical trials that have established what these indications are,” said Steven J. Yakubov, MD, FACC, FSCAI, John H. McConnell Chair of Advanced Structural Heart Disease; system chief of OhioHealth Structural Heart Disease; and medical director of OhioHealth Research Institute.

Intermediate-risk trials

Clinical outcomes after TAVR appear to be similar to those with surgical AVR in intermediate-risk patients, according to Yakubov.

For instance, SURTAVI showed that there were no differences in mortality or disabling stroke with TAVR using the CoreValve System (Medtronic) vs. surgical AVR in an intermediate-risk patient population. Additionally, NYHA functional class improved from class III to class I in about 70% of patients.

A closer look at 30-day clinical outcomes also indicated no significant differences between the two treatment groups in mortality, stroke and major bleeding. There were more blood transfusions, kidney injury and atrial fibrillation in the surgical AVR group, and more pacemaker implantation in the TAVR group, which were roughly comparable outcomes, he noted.

Yakubov also discussed the NOTION trial. The study’s patients had a Society of Thoracic Surgeons risk score of about 2.9%, although most patients would have been classified as intermediate risk, he said.

Similar to SURTAVI, all-cause mortality was similar between patients who underwent TAVR and those who underwent surgical AVR. Further, the effective orifice area and the gradients that were achieved with TAVR in the intermediate-risk group are comparable to what has been seen in the high-risk and extreme-risk patient populations.

“These gradients and the effective orifice area are higher in TAVR than they are with surgical AVR, and they appear to be durable,” Yakubov said. “We’re not seeing any degradation in the effective orifice area or an increase in gradients out to 5 years. ... What we’re seeing clinically is truly TAVR valve durability.”

Potential issues

Although the data are promising, Yakubov said trials of TAVR in low-risk patients, including the Medtronic TAVR Low-Risk Trial and PARTNER 3, tend to exclude bicuspid valve disease. Therefore, the effects of TAVR in these patients will likely only be answered using registry data, he said.

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Another concern with low-risk patients is the issue of reduced leaflet valve motion. There is often normalization with anticoagulation, he said, and it can occur across every transcatheter valve as well as in surgical valves.

Paravalvular leak also remains a problem in low-risk patients. Industry, however, has come to the aid of interventional cardiologists by developing better valves, Yakubov said. For example, usually only mild paravalvular leak is seen with the Sapien 3 valve (Edwards Lifesciences). Additionally, the Evolut PRO valve (Medtronic), which has a pericardial wrap on the inner and outer surface at the bottom of the valve, was associated with significant reductions in paravalvular leak in its clinical trial.

Unfortunately, TAVR is still linked to higher rates of pacemaker implantation compared with surgical AVR, but many single-center studies are showing rates in the 5% range, which is closer to what is observed with surgery, Yakubov noted. Although this rate remains higher with the CoreValve valve (Medtronic), he said it is possible to achieve pacemaker rates of 10% with the device.

Current data

Data on TAVR in low-risk populations can be derived from trials already conducted in intermediate-risk patients as well as initial information from low-risk trials, according to Yakubov.

For instance, in SURTAVI, a number of patients had STS scores lower than 4% but were considered to be intermediate risk according to the surgeon. Among patients with lower STS scores, he noted, there was a signal that mortality and stroke outcomes were not worse with TAVR than they were with surgery and may even be slightly better. Similarly, in the NOTION trial in which all patients had STS scores lower than 4%, there was no signal of worsening mortality, stroke or MI in the TAVR arm compared with the surgical AVR arm, and valve durability also appeared to be “excellent,” Yakubov noted.

Early data from the first 125 patients in the Medtronic TAVR Low Risk trial are also promising. In the trial, the patients are matched 1:1 using propensity matching from the STS database. Of these first 125 patients, 80% had conscious sedation, 87% received Sapien 3 valves and 13% received CoreValve valves.

The primary outcome of mortality was 0% at 30 days. The rates of stroke and MI were also 0%. Only one patient had coronary obstruction, which did not result in a significant clinical event, according to Yakubov. Additionally, he noted that the pacemaker implantation rate was 4%, NYHA functional class improved, hemodynamics were good, paravalvular leak was low and other adverse events compared favorably to what has been observed in the intermediate-risk patient population.

PAGE BREAK

“The intermediate-risk trials give us hope that the low-risk trials will provide excellent outcomes,” Yakubov said. “The TAVR issues of old — paravalvular leak, pacemaker rates, stroke, valve durability — are either improving or going away. However, we do need to address and know more about leaflet thrombosis, such as who should be anticoagulated and who is at risk, and then the clinical indications, hopefully from low-risk studies, should drive further growth in this field.” – by Melissa Foster

Reference:

Yakubov SJ. TAVR Academy III: Unresolved Issues and Future Directions. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; April 25-28, 2018; San Diego.

Disclosure: Yakubov reports he serves on the medical advisory board for Abbott Vascular, Boston Scientific and Medtronic; he is a steering committee member/proctor for Medtronic; he serves on the advisory board for and has equity interest in BioStar Ventures; and he is a consultant for Foldax and SentreHeart.

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