TAVR in Intermediate-risk Patients: How Low Can We Go?

By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

Dr. Zimmet reports no financial relationships relevant to this field of study.

SYNOPSIS: The first large randomized trial comparing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement in intermediate-risk patients shows similar results with regard to mortality and disabling stroke, with TAVR showing an advantage among patients eligible for transfemoral access.

SOURCE: Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016 Apr 2 [Epub ahead of print].

When transcatheter aortic valve replacement (TAVR) was approved in the United States in late 2011, the procedure was initially restricted to patients who were at prohibitive risk of open surgical aortic valve replacement (SAVR). The indication was soon expanded to include the well-studied “high-risk” population, where the field has remained for the past several years.

Cohort A of the original Placement of Aortic Transcatheter Valve (PARTNER) trial randomized patients with severe aortic stenosis (AS) and a high risk of operative mortality to treatment with either SAVR or the Sapien transcatheter valve. High risk was defined as either a Society of Thoracic Surgeons (STS) predicted risk of mortality of at least 10% or an expected risk of mortality of at least 15% as determined by two cardiac surgeons. Mortality was similar in the two groups at one and five years. Similarly, the CoreValve U.S. Pivotal Trial compared SAVR with CoreValve in a high-risk population, which was defined as an expected risk of mortality of at least 15% as determined by two cardiac surgeons, where the STS risk score was one of several factors in this determination. CoreValve demonstrated improved survival vs. SAVR at both one- and two-year time points.

Based largely on these results, the 2014 American College of Cardiology/American Heart Association guidelines for management of patients with valvular heart disease recommended TAVR for patients with severe AS who are at prohibitive risk for SAVR and with an expected survival > 12 months. TAVR is also labeled a reasonable alternative to SAVR in patients with severe AS who are at high risk for surgery. Current guidelines recommend SAVR in intermediate- and low-risk patients.

The most recently published study includes the first large randomized trial of TAVR vs. SAVR in the intermediate-risk population. The PARTNER 2 trial randomly assigned 2,032 patients with severe AS and intermediate surgical risk to TAVR or SAVR. Intermediate risk was defined primarily as an STS predicted risk of mortality of between 4% and 8%, although patients with a score < 4% could be enrolled based on expert opinion in the presence of significant comorbidities not represented in the risk model. Of enrolled patients, 1,011 were assigned to TAVR and 1,021 to surgery. Within the TAVR group, 236 patients presented with vascular anatomy unsuitable for transfemoral delivery and underwent either transapical access (174 patients) or transaortic access (62 patients). Of 94 patients enrolled who did not undergo the procedure, the majority (77 patients) were in the surgical group. The most common reason for withdrawal in this subset was a decision not to undergo surgery after randomization.

The primary endpoint was death from any cause or disabling stroke at two years, and was similar in the transcatheter and surgical groups (19.3% vs. 21.1%; hazard ratio [HR] in the TAVR group, 0.89; 95% confidence interval [CI], 0.73-1.09; P = 0.25). In the predefined transfemoral access subset, TAVR resulted in a lower rate of death or stroke compared with surgery (HR, 0.79; 95% CI, 0.62-1.00; P = 0.05), while the transthoracic-access cohort showed no significant difference compared with SAVR. Although major vascular complications were higher in the TAVR group (7.9% vs. 5.0%; P = 0.008), several other adverse outcomes increased in the surgical group relative to TAVR. These included life-threatening bleeding (43.4% vs. 10.4%; P < 0.001), acute kidney injury (3.1% vs. 1.3%; P = 0.006), and new-onset atrial fibrillation (26.4% vs. 9.1%; P < 0.001). The need for new permanent pacemakers was not significantly different between TAVR and SAVR groups (8.5% and 6.9%, respectively; P = 0.17). Consistent with prior studies, TAVR resulted in larger effective aortic valve areas compared with SAVR, but also had higher rates of paravalvular aortic regurgitation.

The authors concluded that transcatheter and surgical aortic valve replacement in an intermediate-risk population have similar rates of death and disabling stroke at two years.

COMMENTARY

With improvements in device design and growing experience and comfort with the TAVR procedure, there has been a gradual (and some would say inevitable) creep toward application of this technology in lower-risk patients. This move has already begun, but has been without solid supporting evidence — until now. PARTNER 2 is the first large randomized trial comparing this procedure with open surgery in the so-called intermediate-risk population. The Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial, using the CoreValve platform in intermediate-risk patients, has completed enrollment but has not yet reported results.

We should note that, in this fast-moving field, the device used in this trial is already out of date. The Sapien XT, the second-generation device produced by Edwards, has been succeeded by the Sapien 3, which is lower profile and has an external sealing mechanism to reduce paravalvular leak. It is likely that a higher percentage of patients would be eligible for a transfemoral procedure with the newer device, and the current data suggest a clear advantage to TAVR in terms of hard events with the transfemoral approach.

Although patients in PARTNER 2 were lower risk than those previously studied, they were still in the highest quintile of risk compared with patients undergoing SAVR in the United States. Patients in this trial would still be labeled high risk by many — they had an average age of > 81 years, more than 75% were NYHA class III or IV, and more than 65% had concomitant obstructive coronary disease. Cardiologists certainly are not ready to extrapolate these data to younger or to low-risk patients. One significant wild card with respect to application to younger patients is the longevity of TAVR valves as compared with surgically implanted valves. These data will take years to accrue. The FDA recently approved both the Sapien and the CoreValve TAVR platforms for TAVR trials in low-risk patients. Expect more data soon.