April 11th, 2011
PARTNER A: An Investigator’s View
CardioExchange welcomes Dr. Michael Mack to discuss the results of the PARTNER study of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (AVR) in patients with aortic stenosis, which were just released at the ACC meetings in New Orleans. Dr. Mack was one of the principal investigators in this and the recently published PARTNER B study of TAVI in AS patients who were turned down for AVR. Questions to Dr. Mack come from CardioExchange’s Dr. Richard A. Lange and Dr. L. David Hillis.
Background: The PARTNER study showed that TAVI was noninferior to AVR with respect to 1-year mortality in high-risk patients with severe aortic stenosis.
Lange and Hillis: The investigators enrolled patients considered at high risk for adverse effects of AVR (predicted operative mortality, ≥15%), but the 30-day mortality with AVR was only 6.5%. Is AVR better and safer than we appreciate, or are we simply poor at identifying “high-risk” patients? Can we conclude that PARTNER shows that TAVI is an acceptable alternative to AVR for the lower-risk patient?
Mack: The lower observed mortality in the surgical arm could have resulted from either surgery performing better than expected or the risk model overpredicting risk. A study by Thourani and colleagues published in the Annals of Thoracic Surgery in January 2011 reviewed procedural results in very high-risk patients at four PARTNER sites before the trial. The findings demonstrated an expected mortality of 16% and an observed mortality of 16%. Therefore, I feel that the results in the PARTNER study sites were exceptional in the surgery arm. The reason is probably that the surgery was performed in high-volume valve centers with experienced surgeons. The number of surgeons at each PARTNER site was limited to those qualified as high-risk surgeons. Using an STS-predicted mortality of about 4% would include the upper 25th percentile of risk; therefore, in my personal opinion, the as-treated mortality of 5.2% in the TAVI arm in the PARTNER A cohort justifies a hypothesis of equipoise and a trial in this lower-risk population. Having said that, the results of PARTNER A and B were obtained in inoperable and very high-risk patients, and any extrapolation of those results to a lower-risk population and to centers other than high-volume valve centers with a multidisciplinary heart team in place is not justified.
Lange and Hillis: Considering the patients who were included in PARTNER (i.e., elderly, high risk patients) and those who were excluded (i.e., with bicuspid valve, CAD needing revascularization, advanced ileofemoral disease, etc.), what proportion of AS patients currently undergoing AVR would be serious candidates for TAVI?
Mack: Current screening logs of PARTNER study sites indicate that about one third of patients screened were enrolled. Reasons for exclusion included extreme frailty, bicuspid aortic valve disease, not meeting trial criteria, and unwillingness to enter in to an investigational trial. In addition, a fair number of patients died during the workup process or while on the waiting list for the trial. In my opinion, the proportion of screened patients who would be candidates for TAVI outside the confines of a trial might increase to 50% at most. It should be noted that the patients studied (i.e., inoperable or very high-risk) constitute approximately 10% of the current AVR surgical population.
Lange and Hillis: The complication rates for both the AVR- and TAVI-treated patients are impressively low in PARTNER. Since AVR is an established therapy (i.e., the learning curve is over), will TAVI still compare favorably to AVR when it goes “real world”?
Mack: The results of the TAVi arm are especially impressive when it is noted that 19 of the 26 study sites had no previous TAVI experience and that it was an early-generation device. It is true that the arms were somewhat imbalanced: an early-generation technology and technique was being compared with a mature one. However, it should be noted that these results were obtained in high-volume valve centers with experienced structural interventionalists working with a multidisciplinary heart team. I am very concerned that these results are not reproducible at centers where the same treatment paradigm is not in place. As evidence for this, it should be noted that the data from national registries in France and Germany are somewhat worrisome. The 30-day mortality of TAVI procedures continues to be around 8%–10%, even as the logistic EuroSCORE risk of the patients decreases. The fact that the mortality results are not improving and remain quite high may be due to the widespread expansion into the real world, where standalone cardiology centers are often capable of only a transfemoral approach. In the continued access arm of the PARTNER trial in the United States, approximately 50% of the procedures are being performed via a transapical approach, which suggests that a multidisciplinary heart team with all access options available is much more likely to choose a non-transfemoral approach. I am somewhat concerned that the current registry results in Europe suggest that the current PARTNER results will not be reproduced in the real world.
Lange and Hillis: In comparison with AVR, TAVI was associated with a higher incidence of stroke, vascular complications, and paravalvular leak but a lower incidence of atrial fibrillation and bleeding. Are these fair trade-offs? Since most strokes do no not appear to be procedure-related, will improvements in valve design reduce the risk for this complication?
Mack: Currently, the incidence of stroke and vascular complications continues to be an issue of concern with TAVI. We are pursuing in-depth analysis of the stroke data to determine associated factors and whether embolic protection might afford any improvement. We also hope to determine whether there is an ongoing hazard risk after the initial 30-day period. The vascular complication rate appears to be decreasing in our experience and that of other centers, due to newer-generation delivery devices and more experience — both with the procedure and with managing complications — as well as the more-liberal use of the transapical approach in borderline situations. The incidence of paravalvular leak is an ongoing concern and obviously needs long-term follow-up. Although early on there does not seem to be a detrimental aspect to this, it is way too early to assume insignificance.
Lange and Hillis: Without long-term follow-up data available, should we be offering TAVI to younger (i.e., 60-70-year-old) patients?
Mack: I think that offering TAVI to a 60- or 70-year-old patient is currently too much of a stretch. Due to the lack of long-term follow-up data, the higher incidence of bicuspid aortic valve disease in younger patients, and the current mortality and complication rate of TAVI, offering it to this population is not justified. Surgical AVR mortality in this patient group is currently 1% in experienced centers. Studying a population aged 70 or older with multiple comorbidities, such that the predicted mortality is in the range of 4% to perhaps 8%, would probably be more realistic. However, if commercial approval happens before the results of such a trial are available, offering TAVI to patients outside of those similar to the trial study population is not justified.
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