• Cardiology Clinical Trials
• Interventional Techniques & Devices
• Valvular Disease

As many as one-third of patients with severe aortic stenosis are considered unsuitable candidates for surgical aortic valve replacement (AVR) and subsequently have a grave prognosis. An earlier report from the Placement of Aortic Transcatheter Valve (PARNTER; NCT00530894) randomized clinical trial (Cohort B) [Leon MB et al. New Engl J Med 2010] demonstrated that transcatheter aortic valve replacement (TAVR) in inoperable patients dramatically reduced the risk of death over standard medical care (HR, 0.55; 95% CI, 0.4 to 0.74; p<0.001; number needed to treat of 5 patients to prevent 1 additional death at 1 year). Among survivors at 1 year, the rate of cardiac symptoms was also lower in the patients who underwent TAVR. However, these benefits were associated with a significantly increased risk of stroke (5.0% vs 1.1%; p=0.06) and major vascular complications (16.2% vs 1.1%; p<0.001) that were associated with TAVR.

The PARTNER trial now reports that TAVR was noninferior to surgical AVR, the current standard of care, in preventing mortality at 1 year in high-risk patients with symptomatic severe aortic stenosis (Cohort A). The results were presented by Craig R. Smith, MD, Columbia University, New York, New York, USA.

The primary hypothesis was that TAVR would be noninferior to surgical AVR in patients who were deemed high-risk surgical candidates for all cause mortality at 1 year. The study was designed to compare the safety and efficacy of TAVR by either a transfemoral (TF) or transapical (TA) vascular access approach with surgical AVR and was additionally powered to consider the efficacy and safety of TF TAVR individually as a secondary analysis. Patients were required to have symptomatic severe aortic stenosis and be at high surgical risk (ie, a 30-day predicted operative mortality risk ≥15%, as estimated by their Society of Thoracic Surgeons (STS) score). A total of 3105 high-risk patients were screened, and 1057 were enrolled in a 2:1 ratio in the operable (A) and inoperable (B) cohorts of the PARTNER trial. Teams of cardiologists and cardiothoracic surgeons worked together to determine the eligibility of patients and manage their care.

Of the 699 patients who were enrolled in the PARTNER A trial, 492 with adequate femoral/iliac vessel diameter (≥7 mm for the #23 mm valve and ≥8 mm for the #26 mm valve) were randomized to either TF TAVR (n=244) or surgical AVR (n=248). Those with inadequate peripheral vessels (n=207) were randomized to either TA TAVR (n=104) or surgical AVR (n=103).

The primary study endpoint was all-cause mortality at 1 year. Safety endpoints included neurological events (stroke and stroke or transient ischemic attack [TIA]), major vascular complications, major bleeding, repeat hospitalization, new pacemaker requirement, new-onset atrial fibrillation (AF), procedural events, and surgical complications. Cardiac symptoms, 6-minute walk test, and echo assessment of valve performance were used to measure clinical effectiveness. All patients were followed for at least 1 year, and only 2 patients were lost to follow-up. All analyses were considered by intention-to-treat, although 42 patients were not treated as assigned.

Randomized patients appeared to represent those with severely symptomatic aortic stenosis well (mean valve area was 0.7 cm² and mean aortic valve gradient was 43 mm Hg) and were well balanced between treatment groups. Patients were of advanced age (mean 84 years), and there were nearly equal numbers of women and men. The mean STS score was 11.8, and over 90% had NYHA class III or IV cardiac symptoms with a mean left ventricular ejection fraction of 53%. The vast majority of patients had prior coronary artery disease, almost one-third of patients had prior cerebrovascular disease, 43% had undergone prior coronary artery bypass grafting, and 42% had prior peripheral vascular disease. On average, TAVR reduced procedure time by 2 hours and intensive care unit stay by 2 days.

Mortality at 1 year was 26.8% in those who received surgical AVR compared with 24.2% for TAVR (HR, 0.93; 95% CI, 0.71 to 1.22; p=0.001 for noninferiority; p=0.62 for superiority). Among those within the TF subgroup, TAVR was noninferior compared with surgical AVR (22.2% vs 26.4%; HR, 0.83; 95% CI, 0.60 to 1.15; p=0.002 for noninferiority, p=0.25 for superiority). The TA TAVR comparison with surgical AVR was underpowered; however, there was a trend toward increased mortality with TA TAVR, and the investigators did not report the preliminary p-value for noninferiority (29.0% vs 27.9%; HR, 1.22; 95% CI, 0.75 to 1.98; p=0.41 for superiority). Mortality rates at 30 days were lower than expected in both treatment groups, with a trend toward a lower rate with TAVR (3.4%, which is the lowest reported to date for this novel procedure) versus 6.5% for surgical AVR (p=0.07). The operative mortality risk that was estimated by these patients' STS scores was expected to be higher (11%).

Neurological events at 30 days and 1 year were significantly higher in those who underwent TAVR (stroke or TIA occurred in 5.5% vs 2.4% at 30 days; p=0.04; 8.3% vs 4.3% at 1 year; p=0.04), driven predominantly by stroke (Table 1).

Cardiac symptoms by NYHA functional class and distance on the 6-minute walk test showed marked improvement at all time points in both groups. Mean echo gradients at 1 year were clinically similar, with paravalvular aortic regurgitation being greater with TAVR.

The PARTNER trial is a groundbreaking study in the minimally invasive management of valvular heart disease, with the potential to change the standard of practice within cardiology in a manner that has not been seen since the introduction of the coronary stent. If these preliminary results can be replicated with similar clinical effectiveness in routine practice, then transcatheter surgical AVR may be an acceptable alternative therapy to surgical AVR for high-risk patients in the near future. The significance of the trade-off between adverse events that are associated with TAVR versus surgical AVR short and long term requires further exploration.

• © 2011 MD Conference Express