The surprisingly good results from the inoperable PARTNER cohort provides confidence that additional transcatheter aortic valve implantation (TAVI) studies are justified in lower risk aortic stenosis patients and in other selected patient cohorts. The results were published online in the The New England Journal of Medicine and presented by principal investigator Martin B Leon, Columbia University Medical Center, New York, USA at the PCR London Valves Course, London, UK.
Balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery, “and I think we as a community have to alert all healthcare providers managing aortic stenosis patients with symptoms (irrespective of presumed operative status) to contact tertiary care centres for definitive treatment because the alternatives are not good,” said Leon.
“I think PARTNER did represent a paradigm shift in clinical trial design and execution for patients with high risk aortic stenosis. It was interdisciplinary in all respects, meaning that surgeons and interventionalists had equal roles in the study.”
“We screened 3,105 patients with high-risk aortic stenosis, symptomatic patients at a total of 26 sites. As you can see, 1,058 were ultimately enrolled in the study which constituted 34% of the screened patients in two parallel trials. A high-risk study involving 700 patients that were randomised either to surgical aortic valve repair versus either transfemoral or transapical TAVI by depending upon vascular access issues,” he added.
Primary endpoint was all-cause mortality over the duration of the study. Superiority test (two-sided), 85% power to detect a difference, a=0.05, sample size of 350 total patients. The study also had a co-primary endpoint which was a hierarchical composite of all-cause mortality and repeat hospitalisation using a new methodology. The study would be positive if both endpoints achieved p<0.05, or if either endpoint was <0.025.
“A so-called inoperable cohort of 358 patients – a relatively small cohort in the entire embedded PARTNER trial structure of which there are now almost 2,000 patients enrolled and two more randomised trials with the Sapien XT device about to begin in the next several months.”
The main outcomes of PARTNER were that standard therapy did not alter the dismal natural history of patients with severe aortic stenosis and cardiac symptoms because all-cause and cardiovascular mortality at one year was 50.7% and 44.6% respectively.
Transfemoral TAVI, despite limited operator experience and an early version of the system, was associated with acceptable 30-day survival (mortality was 5% after randomisation in the intention-to-treat population and 6.4% as treated).
TAVI was superior to standard therapy, markedly reducing the rate of all-cause mortality by 46%, p < 0.0001, NNT = 5.0 patients, cardiovascular mortality by 61%, p<0.0001, NNT=4.1 patients and all-cause mortality and repeat hospitalisation, hierarchical (FS method), p<0.0001, non-hierarchical (KM analysis) by 54%, p <0.0001, NNT=3.4 patients.
TAVI improved cardiac symptoms (NYHA class, p>0.0001) and six minute walking distance (p=0.002), after one-year follow-up. Dramatic symptom benefits and restoration of normal lifestyle (clear changes by 30 days and continued improvement through one-year follow-up).
TAVI resulted in more frequent complications at 30 days, including major strokes, 5% versus 1.1%, p=0.06. The majority (2/3) were ischaemic and may occurred >30 days post-procedure. “We do not know if those were valve-related and we do not know the association with atrial fibrillation, adjunctive pharmacology and trauma,” he added. Other complications included major vascular complications 16.2% versus 1.1%, p<0.0001 and major bleeding episodes, 16.8% versus 3.9%, p<0.0001 often associated with vascular complications.
“We hope the next generation devices (e.g. Sapien XT and Novoflex) may help to reduce the frequency of procedure-related complications in the future,” said Leon. These results in “inoperable” patients cannot be generalised to other aortic stenosis patient populations and to other TAVI devices, “although I suspect that similar results would be achieved with other devices,” he added.
The ultimate value of TAVI will depend on careful assessment of bioprosthetic valve durability, which will mandate obligatory long-term clinical and echocardiography follow-up of all TAVI patients, the study concluded.