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FDA Approves New CoreValve Low-Risk TAVR Study
Medtronic's CoreValve Evolut R to enroll 1,200 Patients
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CoreValve® Evolut® R Transcatheter Aortic Valve
CoreValve® Evolut® R Transcatheter Aortic Valve
February 23, 2016 -- Medtronic (NYSE: MDT) has announced FDA approval for a new study of transcatheter aortic valve replacement (TAVR). But this trial is different; this trial will be in patients at low-risk for the standard surgical procedure (SAVR). The device will be Medtronic's latest TAVR iteration, the CoreValve® Evolut® R, approved last June by the FDA, and will include 1,200 patients at up to 80 sites.

This new trial, along with the PARTNER III study announced last month by Edwards using the Sapien 3 device, represents a potentially significant expansion in the adoption and implementation of a less invasive treatment for aortic valve disease that may ultimately result in a majority of aortic valve replacements being done via this catheter-based procedure instead of surgery. The much over-used term "game changer" might actually apply here, because it's only been four years since the FDA first approved the original Sapien TAVR device. As Dr. Michael Reardon concluded at the CRT 2016 meeting in Washington, and as quoted by Michael O'Riordan (no relation) of TCTMD, "We’re no longer going to say, who’s a bad candidate for surgery? We’ll be saying, who’s bad for TAVR?"

From Scalpel to Stent
This treatment transition from open invasive surgery to minimally invasive interventional procedures follows the path of coronary artery bypass grafting, AAA repair, carotid endarterectomy, and more: these surgical procedures have given way to their stent/catheter-based counterparts (PCI, EVAR, and CAS); some 50/50, some now the dominant therapy (coronary angioplasty and stenting).

Although equivalent inroads for aortic valve replacement/repair are still years off, approvals for such procedures in low surgical risk patients would represent a major change in treatment, a major advantage for patients, and a major marketing opportunity for those companies with successful devices. Currently Edwards and Medtronic have the only FDA-approved TAVR devices. Boston Scientific and St. Jude may be players in the U.S. market in the near future. But it is Edwards' Sapien 3 and Medtronic's CoreValve Evolut R that will be pushing the indications envelope with these new low-risk studies.

Differences in the Two Low-Risk Trials
Although basically similar, except that the devices are different, the two low-risk studies from Edwards and Medtronic have some differences:

  • The primary endpoint for the Medtronic CoreValve study is all-cause mortality or disabling stroke; for the Edwards Sapien study it's death, stroke and rehospitalization;
  • For CoreValve the number of patients is 1,200 vs. 1,300 for Sapien;
  • For CoreValve the number of sites is 80 vs. 50 for Sapien;
  • The definition of "low-risk" in CoreValve is determined by the heart team's evaluation of the patient with a less than 3% surgical risk; the Sapien study will use an STS score of less than 4%;
  • The age limit in the Sapien trial is 65 years or older; in the CoreValve study, Medtronic is including patients who qualify for surgical prosthesis with no age limit.

Age Factor and Durability
The patient's age is an important factor. Metallic valves have been shown to be longer lasting and so are traditionally the valve of choice for younger patients. Their downside is that they require life-long anti-coagulation therapy, such as warfarin. They also emit a clicking sound, although recipients do become used to it. Furthermore metallic valves can only be implanted via open surgery. Although tissue-based valves have a shorter life (15 years or so) and have been used primarily in elderly patients, the possibility of catheter-based valve-in-valve replacement of such non-metallic valves opens up an alternative treatment for younger patients.

Leaflet Mobility Sub-Study
Based on some CT evidence, there were reports that the mobility of the transcatheter valve leaflets was compromised by thrombotic material. Although in most cases, this was treated successfully with anti-thrombotic drugs, both the Sapien and CoreValve studies have a 400 patient substudy to look at this phenomenon to judge if it is of concern.

More information on the Edwards Sapien 3 study can be found here. More information on the CoreValve study can be found in the press release from Medtronic below:

Medtronic Receives FDA Approval for Expanded Indication Trial in Low-Risk Aortic Stenosis Patients

February 22, 2016 -- Dublin -- Medtronic plc (NYSE: MDT) today announced that the U.S. Food and Drug Administration (FDA) approved an expanded indication trial for the CoreValve® Evolut® R System, the first and only next-generation recapturable, self-expanding transcatheter aortic valve replacement (TAVR) system commercially available in the United States. Patients with aortic stenosis, who are at a low surgical mortality risk as determined by a heart team, will be enrolled in the trial.

Enrollment for the investigational device exemption (IDE) trial is expected to begin during the spring of 2016 and will include 1,200 patients with severe aortic stenosis who have a less than 3 percent risk of mortality, as determined by a heart team. The trial will enroll low-risk patients from up to 80 clinical sites with 1:1 randomization to receive the Evolut R System or undergo open-heart surgery (surgical aortic valve replacement or SAVR). The IDE is designed as an adaptive trial with a primary endpoint of all-cause mortality or disabling stroke. The trial has a 2-year endpoint and allows for a one-year analysis for early FDA submission. Additionally, the trial will include a sub-study of leaflet mobility in 400 patients.

"This trial comes on the heels of data showing patients who underwent TAVR with this self-expanding platform demonstrated superior survival benefit -with low and stable stroke rates- compared to SAVR patients," said Michael Reardon, M.D., professor of cardiothoracic surgery at Houston Methodist DeBakey Heart & Vascular Center and principal investigator of the IDE study. "This study is an important next step in developing robust clinical evidence to help heart teams understand the potential benefits of TAVR in a broader patient population."

The Evolut R system is optimized to increase conformability and sealing at the annulus, while maintaining supra-annular valve positioning for improved blood flow and hemodynamic performance. The valve is delivered through the EnVeo™ R Delivery Catheter System, which features an InLine Sheath that provides the lowest profile on the market (14 Fr equivalent, less than 1/5 inch). The low profile enables treatment of patients with vessels down to 5mm through the preferred transfemoral access route, and may minimize the risk of major vascular complications in some patients.

"Medtronic is committed to expanding access to TAVR for patients who may benefit based on a robust clinical evidence portfolio," said Rhonda Robb, vice president and general manager of the heart valve therapies business, which is part of the Cardiac and Vascular Group at Medtronic. "We are excited to partner with such proven heart teams to study the CoreValve Evolut R self-expanding platform in this low risk patient population."

The CoreValve Evolut R transcatheter valve and the CoreValve EnVeo R Delivery Catheter System were FDA-approved for commercial use in the United States in June 2015. It is also available in Europe and other countries that recognize the CE Mark.

In collaboration with leading clinicians, researchers and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular disease and cardiac arrhythmias. The company strives to offer products and services that deliver clinical and economic value to healthcare consumers and providers around the world.

About Medtronic
Medtronic plc (, headquartered in Dublin, Ireland, is among the world's largest medical technology, services and solutions companies - alleviating pain, restoring health and extending life for millions of people around the world. Medtronic employs more than 85,000 people worldwide, serving physicians, hospitals and patients in approximately 160 countries. The company is focused on collaborating with stakeholders around the world to take healthcare Further, Together.

Any forward-looking statements are subject to risks and uncertainties such as those described in Medtronic's periodic reports on file with the Securities and Exchange Commission. Actual results may differ materially from anticipated results.

Reported by Burt Cohen, February 23, 2016