Panel: SAPIEN Valve Safe, Effective for High-Risk Patients

GAITHERSBURG, MD. – The benefits of Edwards SAPIEN transcatheter heart valve outweigh its risks for older patients with severe, symptomatic aortic stenosis who are at a high risk for surgery, voted the majority of an advisory panel to the Food and Drug Administration on June 13.

All panel members also voted that the valve was effective, and 10 of 12 members said that it was safe. Two members said no to the safety issue.

If approved by the FDA, the valve’s indications will expand its application to a wider group of patients.

The valve entered the U.S. market last November after receiving FDA approval for patients who have severe aortic stenosis and are deemed too sick to undergo surgical heart valve replacement (Cohort B of the pivotal PARTNER trial). (N. Engl. J. Med. 2010;363:1597-607)

On June 12, Edwards Lifescience, the makers of the SAPIEN transcatheter heart valve, said that based on the results of the PARTNER pivotal trial, the valve is also safe and effective in the high-risk cohort (Cohort A) when used according to approved labeling.

Although FDA officials agreed that the trial met its primary end points, they expressed concern with the higher risk of stroke in patients who underwent transcatheter aortic valve replacement (TAVR), compared with those who underwent surgery. They also raised questions about the long-term durability of the device, for which there are no data yet available yet.

In his final remarks, Dr. Craig R. Smith, chair of the department of surgery at Columbia University and coprinciple investigator of the PARTNER trial, said that although the risks associated with the procedures must be taken seriously, they should not an obstacle to the indication’s approval.

The panel’s recommendation is not a definitive predictor of the FDA’s final decision, but if the valve is eventually approved for such indication, "there will be a tendency to say to everybody that we have a winner," said David C. Naftel, Ph.D., a voting member of the panel from the University of Alabama, Birmingham. "But it’s not a winner, it’s a noninferiority trial."

The main results of the cohort A trial showed that all-cause mortality at 30 days favored TAVR at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin, yet again, neurologic complications occurred more frequently after TAVR.

Stroke was a major secondary end point and was defined as a focal deficit lasting greater than 24 hours or a focal deficit lasting greater than 24 hours with positive neuron-imaging studies. Each event was adjudicated in a blinded review by an independent clinical events committee and subclassified (ischemic, hemorrhagic, or undetermined etiology).

Surgical valve replacement has evolved over the past 50 years, and although TAVR is radical, it’s the next logical step in that evolution, Dr. Smith told the panel. The results of the cohort A of PARTNER, he said, bring the field one step closer to the day that valves can be replaced with no large incisions, no heart-lung machine, and potentially no general anesthesia.

The Centers for Medicare and Medicaid Services decided in May that it will cover the procedure in inoperable patients, under certain conditions, including the presence of a heart team during the procedure and evaluation of the patient by two cardiac surgeons.

Heart teams, collaboration between industry and cardiology societies, and continuing development of the TVT registry were also discussed during the meeting.

Dr. Gregory J. Dehmer, professor of medicine at Texas A&M University, said that the field was only at its infancy. In 35 years, a similar panel might be discussing the transradial approach to TAVR, he said, pointing to his wrist.

Dr. Naftel and Dr. Dehmer had no disclosures. Dr. Smith is a coprinciple investigator for the PARTNER trial.

GAITHERSBURG, MD. – The benefits of Edwards SAPIEN transcatheter heart valve outweigh its risks for older patients with severe, symptomatic aortic stenosis who are at a high risk for surgery, voted the majority of an advisory panel to the Food and Drug Administration on June 13.

All panel members also voted that the valve was effective, and 10 of 12 members said that it was safe. Two members said no to the safety issue.

If approved by the FDA, the valve’s indications will expand its application to a wider group of patients.

The valve entered the U.S. market last November after receiving FDA approval for patients who have severe aortic stenosis and are deemed too sick to undergo surgical heart valve replacement (Cohort B of the pivotal PARTNER trial). (N. Engl. J. Med. 2010;363:1597-607)

On June 12, Edwards Lifescience, the makers of the SAPIEN transcatheter heart valve, said that based on the results of the PARTNER pivotal trial, the valve is also safe and effective in the high-risk cohort (Cohort A) when used according to approved labeling.

Although FDA officials agreed that the trial met its primary end points, they expressed concern with the higher risk of stroke in patients who underwent transcatheter aortic valve replacement (TAVR), compared with those who underwent surgery. They also raised questions about the long-term durability of the device, for which there are no data yet available yet.

In his final remarks, Dr. Craig R. Smith, chair of the department of surgery at Columbia University and coprinciple investigator of the PARTNER trial, said that although the risks associated with the procedures must be taken seriously, they should not an obstacle to the indication’s approval.

The panel’s recommendation is not a definitive predictor of the FDA’s final decision, but if the valve is eventually approved for such indication, "there will be a tendency to say to everybody that we have a winner," said David C. Naftel, Ph.D., a voting member of the panel from the University of Alabama, Birmingham. "But it’s not a winner, it’s a noninferiority trial."

The main results of the cohort A trial showed that all-cause mortality at 30 days favored TAVR at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin, yet again, neurologic complications occurred more frequently after TAVR.

Stroke was a major secondary end point and was defined as a focal deficit lasting greater than 24 hours or a focal deficit lasting greater than 24 hours with positive neuron-imaging studies. Each event was adjudicated in a blinded review by an independent clinical events committee and subclassified (ischemic, hemorrhagic, or undetermined etiology).

Surgical valve replacement has evolved over the past 50 years, and although TAVR is radical, it’s the next logical step in that evolution, Dr. Smith told the panel. The results of the cohort A of PARTNER, he said, bring the field one step closer to the day that valves can be replaced with no large incisions, no heart-lung machine, and potentially no general anesthesia.

The Centers for Medicare and Medicaid Services decided in May that it will cover the procedure in inoperable patients, under certain conditions, including the presence of a heart team during the procedure and evaluation of the patient by two cardiac surgeons.

Heart teams, collaboration between industry and cardiology societies, and continuing development of the TVT registry were also discussed during the meeting.

Dr. Gregory J. Dehmer, professor of medicine at Texas A&M University, said that the field was only at its infancy. In 35 years, a similar panel might be discussing the transradial approach to TAVR, he said, pointing to his wrist.

Dr. Naftel and Dr. Dehmer had no disclosures. Dr. Smith is a coprinciple investigator for the PARTNER trial.

GAITHERSBURG, MD. – The benefits of Edwards SAPIEN transcatheter heart valve outweigh its risks for older patients with severe, symptomatic aortic stenosis who are at a high risk for surgery, voted the majority of an advisory panel to the Food and Drug Administration on June 13.

All panel members also voted that the valve was effective, and 10 of 12 members said that it was safe. Two members said no to the safety issue.

If approved by the FDA, the valve’s indications will expand its application to a wider group of patients.

The valve entered the U.S. market last November after receiving FDA approval for patients who have severe aortic stenosis and are deemed too sick to undergo surgical heart valve replacement (Cohort B of the pivotal PARTNER trial). (N. Engl. J. Med. 2010;363:1597-607)

On June 12, Edwards Lifescience, the makers of the SAPIEN transcatheter heart valve, said that based on the results of the PARTNER pivotal trial, the valve is also safe and effective in the high-risk cohort (Cohort A) when used according to approved labeling.

Although FDA officials agreed that the trial met its primary end points, they expressed concern with the higher risk of stroke in patients who underwent transcatheter aortic valve replacement (TAVR), compared with those who underwent surgery. They also raised questions about the long-term durability of the device, for which there are no data yet available yet.

In his final remarks, Dr. Craig R. Smith, chair of the department of surgery at Columbia University and coprinciple investigator of the PARTNER trial, said that although the risks associated with the procedures must be taken seriously, they should not an obstacle to the indication’s approval.

The panel’s recommendation is not a definitive predictor of the FDA’s final decision, but if the valve is eventually approved for such indication, "there will be a tendency to say to everybody that we have a winner," said David C. Naftel, Ph.D., a voting member of the panel from the University of Alabama, Birmingham. "But it’s not a winner, it’s a noninferiority trial."

The main results of the cohort A trial showed that all-cause mortality at 30 days favored TAVR at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin, yet again, neurologic complications occurred more frequently after TAVR.

Stroke was a major secondary end point and was defined as a focal deficit lasting greater than 24 hours or a focal deficit lasting greater than 24 hours with positive neuron-imaging studies. Each event was adjudicated in a blinded review by an independent clinical events committee and subclassified (ischemic, hemorrhagic, or undetermined etiology).

Surgical valve replacement has evolved over the past 50 years, and although TAVR is radical, it’s the next logical step in that evolution, Dr. Smith told the panel. The results of the cohort A of PARTNER, he said, bring the field one step closer to the day that valves can be replaced with no large incisions, no heart-lung machine, and potentially no general anesthesia.

The Centers for Medicare and Medicaid Services decided in May that it will cover the procedure in inoperable patients, under certain conditions, including the presence of a heart team during the procedure and evaluation of the patient by two cardiac surgeons.

Heart teams, collaboration between industry and cardiology societies, and continuing development of the TVT registry were also discussed during the meeting.

Dr. Gregory J. Dehmer, professor of medicine at Texas A&M University, said that the field was only at its infancy. In 35 years, a similar panel might be discussing the transradial approach to TAVR, he said, pointing to his wrist.

Dr. Naftel and Dr. Dehmer had no disclosures. Dr. Smith is a coprinciple investigator for the PARTNER trial.