I’ve sometimes wondered if I’m embarking on the field of surgery in the wrong era. As a medical student, and now as a resident, the big open operations have always seemed to be the most exhilarating and rewarding. It always seems more thrilling to have your hands deep in a patient’s abdomen or chest than lightly grasping and maneuvering small laparoscopic instruments or delicate guidewires. However, as technology evolves, so must medicine and surgery and every specialty seems to be jumping on the bandwagon, including cardiac surgery. It always amazed me that one of the “easiest” and shortest operations in cardiac surgery, an open aortic valve replacement, still required placing a patient on cardiac bypass through a large sternotomy. More recently, though, transcatheter aortic valve replacement (TAVR) has emerged as a less invasive alternative to open aortic valve surgery for patients with severe aortic stenosis. Clinical trials initially tested TAVR in patients at high risk for open cardiac surgery. However, many patients who are referred for aortic valve replacement are low to intermediate risk. With the goal of expanding criteria for TAVR candidates, Leon et al. published the results of the PARTNER 2 trial in this week’s NEJM comparing aortic valve replacement surgery to TAVR in intermediate risk patients.
2032 patients with severe aortic stenosis and intermediate surgical risk (according to Society of Thoracic Surgery criteria) were enrolled in the trial at 57 centers in the United States and Canada. Before randomization, patients were evaluated to assess whether they would be eligible for transfemoral access (if the femoral artery was accessible) or transthoracic access (i.e. transapical or transaortic through an incision in the chest if the femoral artery was not readily accessible) for the TAVR procedure, and then stratified into a transfemoral or transthoracic cohort accordingly. Each cohort was subsequently randomized in a 1:1 fashion to either TAVR or surgical-aortic valve replacement.
The primary endpoint was a composite score of death from any cause or disabling stroke at 2 years with the hypothesis that the TAVR was non-inferior to surgery, with a prespecified noninferiority margin of 1.2 for the upper bound of the hazard ratio. Secondary endpoints included improved aortic-valve areas, frequency of acute kidney injury, severe bleeding, new onset atrial fibrillation, and paravalvular aortic regurgitation.
Among the 2,032 randomized patients, 1,011 were assigned to TAVR and 1,021 were assigned to surgery. There were 236 patients in the TAVR group who had transthoracic access (14%) while the rest were accessed transfemorally. There were no significant differences in the primary endpoint of death from any cause or disabling stroke at 2 years between the 2 treatment arms (19.3% in TAVR and 21.1% in surgery patients, and the hazard ratio (HR) for TAVR was 0.89; 95% confidence interval [CI], 0.73 to 1.09; P = 0.25). The risk ratio at 2 years of the primary endpoint was 0.92 (95% CI, 0.77 to 1.09) which met prespecified noninferiority criteria. There was no difference in the 2 groups between the individual components of the primary endpoint. In an underpowered subgroup analysis of the transfemoral and transthoracic TAVR cohorts, the transfemoral TAVR cohort had reduced rates of death from any cause or disabling strokes compared with surgery but there was no difference in the transthoracic cohort.
At 30 days, major vascular complications were more frequent in TAVR patients, but life-threatening bleeding, acute kidney injury, and new onset atrial fibrillation were more frequent in surgery patients.
Improvement in aortic-valve areas and gradients was significantly greater in the TAVR group at both 30 days and 2 years. However, the frequency and severity of paravalvular aortic regurgitation was greater after TAVR than surgery.
With these encouraging results Dr. Neil Moat asks in his accompanying editorial, “Will TAVR become the predominant method for treating severe aortic stenosis?” He seems to answer in the affirmative but reminds the reader of a few caveats. He notes that although these patients are technically at “intermediate” risk for complications from open surgery according to Society of Thoracic Surgery criteria, they are actually still within the highest quartile of risk which is important to remember when assessing patients with severe aortic stenosis. Another important limitation is that small stented valves were used in the surgery group which has been shown to lead to poorer outcomes, leaving room for improvement in the future. Additionally, cost-effectiveness was not addressed in this trial and while TAVR has been shown to be cost-effective in previous trials in high risk groups, the same may not hold true in low-risk patients. Finally, he concludes that, “As with many trials involving new technologies, the findings have to be interpreted with the understanding that the technology (in both groups) has advanced since the design of the trial.” Both TAVR and surgical technologies have advanced since the start of this trial which makes it harder to generalize the results to current patients.
Alas, this is likely not the last we will hear of the debate as the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) trial (ClinicalTrials.gov number, NCT01586910) has just finished recruitment and further studies involving low risk patients are likely to emerge.
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Andrea Merrill, MD
Andrea was a 2015-2016 NEJM Group Editorial Fellow. She is currently in the middle of her General Surgery residency at Massachusetts General Hospital and is also conducting research focusing on improvements in breast cancer surgery. She plans to pursue a fellowship in Surgical Oncology at the completion of her residency.