After Propensity Matching, Early Mortality Risk Still Evident for Transapical TAVR

New analysis of PARTNER trial data shows that, even after extensive adjustment, there are differences in outcomes between transapical and transfemoral TAVR for high-risk and inoperable patients with aortic stenosis. The findings were published online April 1, 2015, ahead of print in Circulation.

Early mortality risk is greater and recovery slower with transapical compared with transfemoral TAVR. Stroke risk is similar for the 2 groups, while aortic regurgitation (AR) occurs less often following transapical procedures.

“[W]e have identified a group of patients with PAD and other cardiovascular risk factors who are well matched for either [transapical] or [transfemoral] TAVR,” Eugene H. Blackstone, MD, of the Cleveland Clinic (Cleveland, OH), and colleagues write, highlighting the fact that PAD was present in 95% of the patients after propensity matching.

“If it is possible to perform [transfemoral] TAVR in these patients, or becomes possible with smaller delivery systems, they should experience fewer adverse events and faster recovery despite incurring more paravalvular AR,” they add. “At the present time, we recommend a [transfemoral]-first access strategy for TAVR when anatomically feasible.”

Dr. Blackstone and colleagues looked at data on patients enrolled in the randomized and continuing access portions of the PARTNER I trial (both the high-risk and inoperable cohorts). From April 2007 to February 2012, transapical TAVR was performed in 1,100 patients and transfemoral procedures were performed in 1,521. The Sapien valve (Edwards Lifesciences) in 23-mm or 26-mm sizes was used in all cases.

Extensive differences in preprocedural characteristics were seen between the transapical and transfemoral groups, including greater prevalence of cardiovascular risk factors and PAD in the transapical group. Propensity matching based on 111 preprocedural variables resulted in 501 pairs (mean age 85 years; 45% female).

After matching, procedure time was similar between access types, although the transapical approach was associated with a shorter median fluoroscopy time (12 vs 22 minutes) and lower contrast volume (90 vs 120 mL; P < .0001 for each). Also, transapical patients were more likely to receive the 26-mm valve (53% vs 45%; P = .016), although median cover index (ratio of the difference between prosthesis size and annulus diameter in systole to prosthesis size) was similar for both approaches.

Patients who underwent transapical TAVR were more likely to die in the hospital and to receive blood transfusions, but there were no differences between groups in the rates of major bleeding, pacemaker implantation, MI, or stroke. Transapical patients stayed in the hospital longer after the procedure (table 1).

Patients also had slower recovery after transapical TAVR. At 30 days, they were less likely than transfemoral patients to be in NYHA class I (31% vs 38%; P = .0003), although there was no difference by 6 months (51% vs 47%; P = .50).

The elevated mortality risk in the transapical group remained evident through 6 months (19% vs 12%; P = .01), with the gap narrowing by 3 years (47% vs 45%). Stroke risk remained similar between groups throughout follow-up.

After transapical procedures, patients were less likely to have moderate-to-severe AR at discharge (8.9% vs 12%; P = .001) and at 6 months (10% vs 15%; P < .0001). Similar differences were seen for mild AR. Among the patients who received the 23-mm valve, transfemoral patients had more paravalvular AR at discharge, 30 days, and 6 months, but among those who received the 26-mm valve, the rate was higher among transfemoral patients at discharge only.

Difference Possibly Relates to Thoracotomy

Prior studies have shown that transapical access is associated with a higher risk of adverse outcomes compared with transfemoral access. This could potentially be due to transapical being an open surgical procedure and to differences in the types of patients who receive 1 type of access over another, the authors say.

“In fact, we found that in the PARTNER trial, other chronic medical conditions besides severe aortic stenosis of patients in these 2 groups are quite different,” Dr. Blackstone and 3 of his coauthors told TCTMD in a group email interview. “Specifically, patients in the [transapical] TAVR group had extensive ‘whole-body’ vascular disease. These differences could well explain differences in outcomes.”

To explore that possibility, the researchers employed propensity matching, “which created 2 groups of patients with extensive vascular disease. The comparison of outcomes now is more apples-to-apples than it was without accounting for these differences,” they noted.

That is important, they added, “because as catheter-based delivery systems used to insert these devices become smaller and more refined, [transfemoral] TAVR (or TAVR through other arteries) will be applied in the future to more and more patients that look like PARTNER I [transapical] TAVR patients, and this tells us the kind of outcomes we should expect to see.”

Before matching, it was possible to think that the baseline differences among patients might explain the discrepancy in early mortality, Dr. Blackstone and coauthors wrote in the email. “What we have shown in very well-matched patients is that this is not the case. The difference seems to be attributable to the thoracic surgical procedure, for which a thoracotomy is performed.” 

Newer access routes, including transaortic and trans-subclavian, may help minimize the risk, although “time will tell if these are safer routes,” they wrote.

Newer Studies to Provide Context

In their paper, the researchers say that future research involving newer devices “will put these early results, which reflect the outcomes of large second-generation TAVR devices used in high-risk patients, into proper context.

“With smaller valve and deployment systems, greater technical facility, and refined patient selection, outcomes are anticipated to improve. Whether the mortality superiority of the [transfemoral] approach identified in the current report will persist in third- and fourth-generation device trials and lower-risk patient cohorts is unknown,” they continue, adding that the ongoing PARTNER II and SURTAVI trials will provide new information.

In the meantime, the authors caution against interpreting the observed differences as reflecting cause and effect, however. They concede that propensity matching may have missed important factors that could impact treatment, including frailty or “latent processes of the event.”

“Although we were criticized for using propensity matching in this nonrandomizable situation, it is a powerful tool of comparative-effectiveness research that gets us much closer to ‘the truth’ than comparisons of very different populations with no accounting for the their underlying differences,” Dr. Blackstone and coauthors said in their email.

Note: Several authors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Source:
Blackstone EH, Suri RM, Rajeswaran J, et al. Propensity-matched comparisons of clinical outcomes after transapical or transfemoral TAVR: a PARTNER-I trial substudy. Circulation. 2015;Epub ahead of print.

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