The CoreValve extreme surgical risk trial was a multi-center, nonrandomized trial evaluating the safety of self-expanding TAVR (CoreValve) for the treatment of severe symptomatic aortic valve stenosis in patients at extreme surgical risk. Extreme surgical risk was defined as a 50% or greater risk of mortality or irreversible morbidity by 2 cardiac surgeons and 1 interventional cardiologist. The primary endpoint was a composite of all-cause mortality or major stroke at 12 months. A total of 41 centers in US participated enrolling 506 patients. The rate of the primary end point was 26.0% compared to the pre-specified performance goal of 43.0%. Important 30-day secondary end points included all-cause mortality (8.4%), major stroke (2.3%), and need for permanent pacemaker (21.6%).
The Increased Risk CoreValve trial was a multi-center, randomized controlled trial comparing a self-expanding, supraannular TAVR (CoreValve) to surgical aortic valve replacement in increased surgical risk patients. The trial was conducted at 45 centers and randomized 795 patients. Increased surgical risk was determined by 2 cardiac surgeons and 1 interventional cardiologist and was defined as an estimated 30-day risk of death >15% and risk of death or irreversible complications <50%. The mean STS score was 7.3% in the TAVR group and 7.5% in the surgical group. The primary end-point of rate of death from any cause at 1-year was reached in 14.2% of the TAVR arm and 19.1% in the surgical arm, meeting criteria for noninferiority (p<0.001) and superiority (p=0.04) of TAVR. The 30-day rate of any stroke was 4.9% in the TAVR group vs. 6.2% in the surgical group (p=0.46). In the as-treated population, the rate of permanent pacemaker implantation was 19.8% for TAVR vs. 7.1% for SAVR (p=<0.001). Major vascular complications, acute kidney injury, and now-onset atrial fibrillation were all reduced in the TAVR group.
The SURTAVI trial was a multi-center, randomized controlled trial comparing the supraannular, self-expanding TAVR (CoreValve 84% and Evolut R 16%) device vs. surgical aortic valve replacement in symptomatic severe aortic stenosis patients at intermediate surgical risk (STS risk >3%). SURTAVI included 87 centers and enrolled 1746 patients. There was no significant difference between the primary end-point of death from any cause or disabling stroke at 2-years 12.6% for TAVR vs. 14.0% for surgery, meeting criteria for noninferiority of TAVR. The 24-month rate of disabling stroke favored TAVR 2.6% vs. 4.5%, whereas there was no difference in death from any cause (11.4% vs. 11.6%). The rate of new permanent pacemaker in 30-days after treatment was 25.9% for TAVR vs. 6.6% for SAVR (95% CI 15.9-22.7).
Published in tandem with the low-risk Sapien trial, the Evolut Low Risk trial was a multi-center, randomized controlled trial comparing the self-expanding supraannular Evolut platform (either CoreValve 3.6%, Evolut R 74.1%, or Evolut PRO 22.3%) TAVR device vs. surgical aortic valve replacement in symptomatic severe aortic stenosis patients at low surgical risk. The trial included 86 centers and 1468 patients were enrolled. The mean STS risk score was 1.9%. The primary end point was a composite of death or disabling stroke at 24-months for noninferiority. The primary end point was estimated at 24-months to be 5.3% in the TAVR group vs. 6.7% in the surgical group p<0.001 for noninferiority. There were statistically significant differences in secondary end points at 30-days between TAVR and SAVR including disabling stroke (0.9% vs. 2.8%), bleeding complications (2.4% vs. 7.5%), moderate or severe aortic regurgitation (3.5% vs. 0.5%) and pacemaker implantation (17.4% vs. 6.1%). These results lead to FDA approval for the use of TAVR in symptomatic severe aortic stenosis of all surgical risk levels.