ACC 2019 – Low risk of patients being denied transcatheter aortic valves

The battle for dominance of the transcatheter aortic valve market has shifted to new territory. And once again, Edwards Lifesciences is winning.

Catheter-based aortic valve implants have already become standard therapy for patients who are at risk of death or complications were they to be treated surgically. Now even patients who can safely undergo surgical implantation are likely to be treated with these minimally-invasive devices, opening up a substantial new market for their developers.

Medtronic’s latest-generation aortic prosthesis, CoreValve Evolut R, has been proven non-inferior to surgery in low-risk patients. But Edwards Lifesciences can go one better, with its Sapien 3 device having shown superiority to surgery. And a recap of US approval trial data over the last decade shows how thoroughly Edwards has taken control of this space.

The first data backing the use of these devices came in 2010, when Edwards' first-generation Sapien valve was shown to be as good as – indeed, numerically better than – drug therapy in patients who could not have surgery. It was approved by the FDA for this population the following year; Medtronic’s CoreValve followed Sapien to market in 2014. 

Trial data in high- and medium-risk patients followed, and while Edwards’ trials reported before Medtronic’s, the lag between the corresponding FDA approvals narrowed. The two groups’ upcoming approval decisions in the low-risk group might arrive at roughly the same time – and both surely will be approved. 

This is a vast group of potential patients – as many as half of heart valve replacement candidates have a low risk of surgical complications.

An edge for Edwards

Data presented at the annual meeting of the ACC this week showed that both devices performed well in low-risk patients – but were by no means equally impressive. 

Trial summary: Sapien and CoreValve
Extreme-risk (inoperable) patients
Device Sapien - Edwards Lifesciences CoreValve - Medtronic
Primary endpoint Partner (NCT00530894) cohort B NCT01240902
Mortality at one year 31% vs 51% for best medical therapy
p<0.001 for noninferiority
Mortality or major stroke at one year   25.5% vs prespecified goal of 43%
p<0.001 for noninferiority
Approval date November 2, 2011 January 17, 2014
High-risk patients
Device Sapien - Edwards Lifesciences CoreValve - Medtronic
Primary endpoint Partner (NCT00530894) cohort A NCT01240902
Mortality at one year 24.2% vs 26.8% for surgery
p=0.001 for noninferiority
14.2% vs 19.1% for surgery
p<0.001 for noninferiority; p=0.04 for superiority
Approval date October 19, 2012 June 12, 2014
Intermediate-risk patients
Device Sapien XT/Sapien 3 - Edwards Lifesciences CoreValve/CoreValve Evolut R - Medtronic
Primary endpoint Partner II (NCT01314313) Surtavi (NCT01586910)
Mortality or disabling stroke at two years 19.3% vs 21.1%  for surgery
p=0.001 for noninferiority
12.6% vs 14% for surgery
posterior probability of noninferiority >0.999
Approval date August 18, 2016 June 10, 2017
Low-risk patients
Device Sapien 3 - Edwards Lifesciences CoreValve Evolut R - Medtronic
Primary endpoint Partner 3 (NCT02675114) Evolut Low Risk (NCT02701283)
Mortality, stroke or rehospitalisation at one year 8.5% vs. 15.1% for surgery
p<0.001 for noninferiority; p=0.001 for superiority
Mortality or disabling stroke at two years   5.3% vs 6.7% for surgery
posterior probability of noninferiority >0.999
Approval date Expected Q2/Q3 2019 Expected Q2/Q3 2019
Source: NEJM; company communications.

Most obviously, Edwards’ Sapien 3 was proven superior to surgery in low-risk patients, whereas the best Medtronic’s CoreValve Evolut R could muster was noninferiority (the pre-specified criterion for superiority – posterior probability of at least 0.779 – was not met). 

Comparing data from two different trials is never ideal, and the differing endpoints used in these studies make this tricky. Partner 3, the 1,300-patient trial of Edwards’ Sapien 3, used all-cause mortality, all stroke, and rehospitalisation at one year as the key outcome, while Medtronic’s 1,468-patient Evolut Low Risk trial used all-cause mortality or disabling stroke at two years.

A Medtronic spokesperson told Vantage that all-cause mortality or disabling stroke at two years was chosen for the Evolut study owing to its significance as a hard primary endpoint, arguing that the inclusion of rehospitalisation in the Evolut study’s primary endpoint would have likely resulted in a finding of superiority, as well.

Medtronic's CoreValve Evolut Pro valve

Still, superiority counts for a lot, and it is generally the shared opinion among cardiologists and sellside analysts that Edwards has come out the winner. 

One particularly important consideration for cardiologists choosing a valve to use in a low-risk patient is the rate of pacemaker implantation, and here Medtronic suffered badly. 17.4% of CoreValve Evolut R recipients needed a permanent pacemaker, nearly three times as many as in the control group. In Edwards’ trial, only 2.4% of Sapien 3 patients needed a pacemaker, a lower proportion than in the surgical group.

This not only suggests that Sapien 3 is less disruptive to heart rhythms, but also means that using this valve is likely to be cheaper overall than using CoreValve Evolut R.

The overall expectation is that these new data will boost usage of catheter-mounted valves. Stifel analysts wrote that after the low-risk approvals come through sales could increase 27% year-on-year. The segment is currently worth around $3.8bn globally, with Edwards having a share of about 60% to Medtronic’s 34% – the rest belongs to Boston Scientific, whose Lotus device is sold in Europe but has not yet reached the US.


Some questions have been answered by the ACC studies, but at least one big issue will not be resolved for some time: durability. Low-risk patients are, of course, younger and healthier on average than those in higher risk cohorts. The devices must last for decades, and there has not been enough time since the first implants, which occurred in the mid-2000s, to assess this. 

More cautious cardiologists treating younger patients might wish to opt for surgical valves, which have been around in recognisable forms since the ’70s. 

That said, the fact that percutaneous implantation is less traumatic and requires shorter recovery than surgery gives Edwards and Medtronic a persuasive counter-argument. And so far, there has been nothing to suggest transcatheter valves are any less durable than surgical implants, and a great deal to suggest they are as effective. In the case of Sapien, they could even be better. 

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