PARTNER Analyses Highlight Mortality Curves After TAVR

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In newly released details on mortality in the PARTNER trial, transcatheter aortic valve replacement (TAVR) gave inoperable patients an additional 6 months of life expectancy over 2.5 years compared with standard therapy. Among high-risk patients, transfemoral TAVR also increased survival, though it carried a slightly higher risk of cardiovascular death than did surgery, reports a paper published in the July 15, 2014, issue of the Journal of the American College of Cardiology.

As such, transfemoral TAVR “should be considered the standard of care for eligible inoperable patients with severe symptomatic [aortic stenosis] or at high risk of noncardiovascular mortality after conventional surgery,” the PARTNER researchers conclude. 

Methods
Lars G. Svensson, MD, PhD, of the Cleveland Clinic (Cleveland, OH), and colleagues sifted through data from both arms of the PARTNER (Placement of Aortic Transcatheter Valves) trial:
  • Cohort A, which included high-risk patients randomized to surgery (n = 351) or TAVR (n = 244 transfemoral and 104 transapical)
  • Cohort B, which included inoperable patients randomized to standard therapy (n = 179; with or without balloon aortic valvotomy) or TAVR (n = 179, all transfemoral) 
The main trial found TAVR noninferior to surgery in Cohort A and superior to standard therapy in Cohort B.


Transfemoral TAVR Comes out Ahead

In Cohort A, 20 of the 275 patients who died did so in the time between randomization and the procedure. Risk of death peaked early after both transapical TAVR and surgery, “falling within 3 to 6 months to a low level commensurate or better than that of the matched US population estimates,” Dr. Svensson and colleagues note. Early risk after transfemoral TAVR, they add, was “only modestly elevated” and gradually dovetailed with the other curves within 2 years. 

A higher proportion of deaths were cardiovascular vs noncardiovascular or of unknown cause in the transfemoral TAVR group compared with the transapical TAVR and surgery groups (table 1). 

Table 1. Distribution of Death Types Among High-Risk Patients

 

Transfemoral TAVR

Transapical TAVR

Surgery

Cardiovascular

37%

22%

33%

Noncardiovascular

43%

41%

43%

Unknown Cause

20%

37%

24%

 

Transfemoral TAVR increased lifespan by 0.13 years over the 2.5 years after randomization compared with surgery and 0.22 years compared with transapical TAVR. 

In Cohort B, transfemoral TAVR again imparted no spike in risk of early death between randomization and treatment, but patients randomized to standard therapy had a peak possibly related to balloon aortic valvotomy. Survival diverged between the 2 arms within 30 to 60 days and continued to widen, such that by 2.5 years, transfemoral added a net lifetime of 0.50 years compared with standard therapy. 

For both the standard therapy and transfemoral TAVR groups, most deaths were cardiovascular (table 2).

Table 2. Distribution of Death Types Among Inoperable Patients

 

Standard Therapy

Transfemoral TAVR

Cardiovascular

49.6%

39.2%

Noncardiovascular

15.6%

31.4%

Unknown Cause

34.8%

29.4%

 

Most cardiovascular deaths in PARTNER were related to heart failure and sudden death, while noncardiovascular deaths arose mainly from infection, respirator complications, and malignancies. Only 4 deaths were specifically device-related, all involving endocarditis due to a prosthetic valve.

 Curves Offer Clinical Lessons

Although many of the mortality patterns that emerged from PARTNER will be familiar to readers, the investigators write, “an important novel finding is that early risk after randomization to [transfemoral TAVR in both cohorts] was substantially lower than after [transapical TAVR or surgery]. Thus, an advantage of a percutaneous approach is a reduction of periprocedural risk, particularly noncardiovascular risk.”

In addition, the study reaffirms “that inoperable patients treated by [transfemoral TAVR] have markedly improved overall survival compared with standard therapy. This was true despite all of the conditions, valve- and non-valve-related, that led to the consensus about inoperability,” they comment.

However, Dr. Svensson and colleagues acknowledge certain limitations to the findings. “Clearly, these patients represented a selected population who underwent rigorous screening,” they say, noting that only one-third of screened patients were enrolled in PARTNER. Nor were the researchers able to ascertain quality-adjusted life years or conduct multivariable analysis to identify differences in risk factors for death among patient subgroups.

Approaches Carry Their Own Risk  

In an editorial accompanying the paper, Giusseppe Bruschi, MD, and Nuccia Morici, MD, of Niguarda Ca’ Granda Hospital (Milan, Italy), propose that the early spike in noncardiovascular mortality for transapical TAVR and surgery may be related to the procedures themselves. For example, they report, respiratory failure accounted for a larger segment of all deaths with transapical TAVR (15%) than with transfemoral TAVR (3.3%) or surgery (6.4%). 

“In addition, the use of the [transapical] approach involves the puncture and the introduction of a large catheter through the ventricular apex (≥ 24 Fr, with external diameter ≥ 7.9 mm),” Drs. Bruschi and Morici point out. “This has been associated with a greater increase (up to 4 times higher) in cardiac biomarkers of myocardial injury with the presence of significant myocardial necrosis at the level of the left ventricular apex in such patients as well as less improvement in left ventricular ejection fraction during follow-up.” 

Agreeing that in high-risk patients transfemoral TAVR should be the standard of care, they conclude: “In the near future, with improvements in valve and sheath technology, more and more patients with a lower risk profile will most likely be treated with [transfemoral TAVR]. However, it is still important to evaluate whether other proximal, less invasive, alternative approaches to [transfemoral TAVR], such as axillary and direct aortic approaches, will lead to better results than [transapical TAVR].”

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

 

 


Sources:
1. Svensson LG, Blackstone EH, Rajeswaran J, et al. Comprehensive analysis of mortality among patients undergoing TAVR: results of the PARTNER trial. J Am Coll Cardiol. 2014;64:158-168.

2. Bruschi G, Morici N. Mortality in the PARTNER trials: transfemoral is better [editorial]. J Am Coll Cardiol. 2014:64:169-171.

 Disclosures:

  • Dr. Svensson reports receiving travel reimbursement from Edwards Lifesciences related to participation as an unpaid member of the executive committee of the PARTNER trial; consultant fees from Abbott, Edwards Lifesciences, Medtronic, and St. Jude; and research grants from Abbott, Edwards Lifesciences, and St. Jude.
  • Dr. Bruschi reports serving as a consultant to Medtronic.

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