TAVR-Surgery Parity at 5 Years, Good Echo Result Key: PARTNER 2A

October 03, 2019

SAN FRANCISCO — The PARTNER 2A trial shows similar rates of death or disabling stroke at 5 years for transcatheter and surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk, just as it had at its 2-year follow-up.

Early functional gains and quality-of-life improvements after surgery or transcatheter aortic valve replacement (TAVR) continued over the long term, with no significant differences between the groups.

Aortic valve hemodynamics were also similar at 5 years between TAVR and surgical aortic valve replacement (SAVR).

That TAVR and SAVR were comparable for the primary end point at both 2 and 5 years reinforces the impact PARTNER 2A has already had on practice. TAVR has made huge inroads into the surgical procedure's share of intermediate-risk patients, as it has started to do for low-surgical-risk patients after the recently published Evolut and PARTNER 3 trials.

But the PARTNER 2A analysis at 5 years had a few lessons to teach about both TAVR and SAVR in intermediate-risk patients that weren't as apparent at the shorter-term follow-up.

For example, patients in the two groups fared as well over 5 years, with primary end point rates of 48% for TAVR and 43% for SAVR (P = .21) overall. But the less-invasive approach faltered compared with surgery in the latter half of that period.

Also, significantly more TAVR than SAVR patients were left with moderate to severe paravalvular regurgitation (PVR) by echocardiography after their procedure. The risk for death or disabling stroke was significantly increased in any patient with such PVR compared twitho negligible PVR or none at all.

Vinod Thourani (Source: Fredy Perojo/Medscape)

And TAVR in the minority of patients who underwent the procedure using transthoracic catheter access did significantly worse than SAVR for death or disabling stroke at 5 years, reported Vinod H. Thourani, MD, Medstar Heart and Vascular Institute, Washington, DC, here at Transcatheter Cardiovascular Therapeutics 2019.

Hazard Ratio (HR) for Death or Disabling Stroke for TAVR vs SAVR in PARTNER 2A by Follow-up Time
Follow-up Time HR (95%CI) P Value
2 years 0.89 (0.73–1.09) .25
5 years 1.09 (0.95–1.25) .21

With those findings comes with the caveat that all patients in the trial, which launched in 2011, received the now-outmoded SAPIEN XT valve, which requires a 16 to 20 F guide catheter, observed Thourani, who is chair of cardiac surgery at his institution. Its successor SAPIEN 3 valve, which uses a 14 to 16 F caliber guide, is used today.

The trial randomly assigned 1011 intermediate-risk patients with severe aortic stenosis to TAVR with the balloon-expandable valve, using either transfemoral or transthoracic access, and 1021 to undergo SAVR.

After about 1 year, the primary end point began a continuous climb among TAVR patients who had the transthoracic approach compared with the SAVR group. The rates were 59.3% and 48.3%, respectively (P = .03), by 5 years.

The rate of death or disabling stroke among the remaining TAVR patients who had the transfemoral procedure, just as with the overall TAVR group, was nonsignificantly different from the rate in the SAVR group, at 44.5% and 42.0%, respectively (P = .80).

Hazard Ratio for Death or Disabling Stroke, TAVR vs SAVR, by Access Route and Follow-up Time
Follow-up Period Transfemoral Transthoracic
Up to 2 years 0.79 (0.62–1.00) 1.21 (0.84–1.74)
Up to 5 years 1.02 (0.871.20) P = .80 1.32 (1.02–1.71) P = .03
2–5 years 1.23 (1.00–1.52) 1.45 (1.01–2.07)

Practice has already moved away from transthoracic TAVR along with valve evolution toward slimmer profiles, making transfemoral access more the norm, Thourani told theheart.org | Medscape Cardiology. These days, only about 4% to 5% of TAVR procedures use the transthoracic route.

When PARTNER 2A started, the transthoracic route was used in "up to 50% of cases," and the rate was about 25% by the trial's end, Thourani said during his formal presentation at the TCT sessions.

"I think those days are over," he said about transthoracic TAVR. Not only is there more PVR using the transthoracic approach, in such cases the ejection fraction continues to fall during follow-up. "And when the ejection fraction falls, they continue to have PVR, and that leads to a cascade of even worse outcomes."

As even SAVR produced better outcomes, surgery appears to be "the preferred alternative to transthoracic TAVR," particularly in patients in whom transfemoral access isn't feasible. The transthoracic approach, Thourani said, "I really see as no-option in current use of the transcatheter valve therapies."

Thourani and his colleagues looked at the primary end point not only at 2 years and at 5 years, but across the discrete interval starting at 2 years and continuing to 5 years in a "landmark analysis."

TAVR and surgery, which were comparable for death or disabling stroke at 2 years and overall at 5 years, showed a divergence in outcomes starting at year 2 that significantly ultimately favored SAVR, Thourani said.

The hazard ratio (HR) for the primary end point was 1.27 (95% CI, 1.06–1.53) for TAVR vs SAVR strictly within the period of 2 years to 5 years.

With regard to the primary end point, "I'm not keen on landmark analyses, so I most lean on the 5-year result," said statistician Stuart J. Pocock, PhD, London School of Hygiene and Tropical Medicine, as a panelist following Thourani's presentation.

"So that's a success, I suppose."

PARTNER 2A also saw that moderate to severe PVR was associated with increased mortality compared with mild PVR (64.8% and 48.7%, respectively; P = .007), and both were more common with TAVR than with SAVR.

Rate of PVR, TAVR vs SAVR, by Severity of PVR and Follow-up Time*
PVR severity (follow-up) TAVR SAVR
Moderate/severe (30 d) 3.8 0.5
Mild (30 d) 22.5 2.0
Moderate/severe (2 y) 8.2 0.6
Mild (2 y) 26.9 3.5
Moderate/severe (5 y) 6.5 0.4
Mild (5 y) 26.8 5.9
*P < .001 TAVR vs SAVR in all PVR categories at all follow-up times

But mortality in patients with mild PVR only trended toward greater significance in patients with "none-to-trace" amounts of PVR, whose 5-year rate was 41.1% (P = .07 vs mild PVR).

Technology improvements have not only obviated most transthoracic TAVRs, they have also brought down the risk for PVR after TAVR. In PARTNER 2A, "paravalvular regurgitation was more common than it would be now," observed Pocock.

"Today the result may be even better if you could now do a SAPIEN 3 randomized trial. The bad news is that will never happen," he said.

Also a panelist, cardiac surgeon Michael A. Borger, MD, PhD, Leipzig Heart Center, Germany, cautioned that mild PVR is many times more common after TAVR than SAVR, even today.

So, he asked Thourani, should it be a concern in the modern era of low-surgical-risk TAVR "to have almost a statistically significant difference in survival at 5 years between mild and none-to-trace" PVR in the intermediate-risk PARTNER 2A patients?

The goal at TAVR is to leave the patient with "less-than mild" PVR, Thourani replied; but if there's mild PVR, "so far when we looked at these data it has not made a major impact on mortality or for other clinical outcomes."

In the TAVR experience with low-surgical-risk patients, "even mild PVR at 1 year was not associated with any change in any of the major events. But that's only at 1 year," Martin Leon, MD, New York-Presbyterian/Columbia University Medical Center, New York City, said from the panel.

Even if there's no PVR early on, he said, over the long term "as much as we can with valve sizing, potentially valve choice, and postdilatation, we should try to eliminate it as much as we can, even mild PVR, and get as close to a surgical result as we can."

PARTNER 2A was funded by Edward Lifesciences. Thourani discloses grant/research support from Edwards Lifesciences, Abbott Vascular, Boston Scientific, JenaValve, and Cryolife; sitting on steering committees for Edwards Lifesciences, Abbott Vascular, Boston Scientific, JenaValve, Cryolife, and Gore Vascular; and honoraria from Edwards Lifesciences, Abbott Vascular, Boston Scientific, JenaValve, Cryolife, and Gore Vascular. Pocock disclosed no relevant financial relationships. Borger reports receiving speaker honoraria and consultant fees to his institution from Edwards Lifesciences, Medtronic, Abbott, and CryoLife. Leon reports grants/personal fees from Edwards Lifesciences, Medtronic, Boston Scientific, Gore Medical, Meril Lifesciences, and Abbott.  

Transcatheter Cardiovascular Therapeutics (TCT) 2019: Late-Breaking Trials 3. Presented September 28, 2019.

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