# TAVR vs. Surgery for Aortic Valve Replacement: Five-Year Results in Low-Risk Patients In a randomized trial of 1,000 patients with severe, symptomatic aortic stenosis (narrowing of the heart's aortic valve), the patients were at low risk for surgery. Transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement produced similar outcomes at five years. The combined rate of death, stroke, or rehospitalization was 22.8% with TAVR and 27.2% with surgery, a difference that was not statistically significant (P=0.07). A second, more detailed analysis that counted death, disabling stroke, nondisabling stroke, and rehospitalization days also showed no significant difference between the two procedures (win ratio 1.17; P=0.25). Valve function remained good in both groups, and bioprosthetic-valve failure (breakdown of the replacement valve) occurred in about 3 to 4 out of every 100 patients in each group. # TAVR vs. Surgery for Aortic Valve Replacement: Five-Year Results in Low-Risk Patients ## Table of Contents - Key Points - Background: Why This Study Matters - How the Study Was Conducted - Who Participated in the Study - What the Researchers Measured - Key Findings at Five Years - Valve Function and Durability - Other Complications and Safety Outcomes - What These Results Mean for Patients - Limitations of the Study - Recommendations for Patients - Frequently Asked Questions - Source Information ## Key Points - In a 1,000-patient trial of low-risk severe aortic stenosis, TAVR and surgery had similar five-year rates of death, stroke, or rehospitalization (22.8% vs 27.2%; P=0.07). - TAVR was linked to less new-onset atrial fibrillation (13.7% vs 42.4%) and less serious bleeding (10.2% vs 14.8%) than surgery. - Valve thrombosis was more common after TAVR (2.5%) than after surgery (0.2%), though events were rare in both groups. - Bioprosthetic-valve failure occurred in about 3 to 4 out of every 100 patients in each group over five years. - The choice between TAVR and surgery should be made by a heart team, considering anatomy, other conditions, and patient preferences. ## Background: Why This Study Matters Aortic stenosis is a condition in which the aortic valve becomes narrowed and cannot open fully. This forces the heart to work harder to pump blood to the body. When the condition becomes severe and causes symptoms, it can be life-threatening without treatment. For many years, open-heart surgery was the standard treatment for severe aortic stenosis. During this surgery, doctors replace the damaged valve with a new one. More recently, a less invasive option called **transcatheter aortic-valve replacement (TAVR)** has become available. TAVR involves threading a new valve through a blood vessel, usually in the groin, and placing it inside the heart without opening the chest. Earlier randomized trials showed that TAVR was at least as good as surgery in patients at intermediate or high risk of dying within 30 days after surgery. Two other randomized trials involving younger, low-risk patients also showed TAVR was noninferior or superior to surgery at two or three years. The PARTNER 3 trial previously reported that at one and two years, patients who received TAVR had significantly lower rates of the combined outcome of death, stroke, or rehospitalization. This was compared with surgery. However, it was unknown whether these benefits would last over a longer period. This study reports the five-year outcomes. ## How the Study Was Conducted This was a multicenter, randomized trial conducted at 71 clinical sites. Patients were assigned by chance in a 1:1 ratio to receive either TAVR with the SAPIEN 3 valve or surgical aortic-valve replacement with a commercially available bioprosthetic valve. A bioprosthetic valve is a replacement valve made from biological tissue. The trial was designed by the sponsor, Edwards Lifesciences, with input from the trial steering committee and the U.S. Food and Drug Administration. An institutional review board at each site approved the study. The sponsor funded all trial activities and participated in site selection, data collection, monitoring, and statistical analysis. Clinical outcomes and echocardiographic data (heart ultrasound measurements) were assessed at several time points. These time points were before the procedure, after the procedure, at hospital discharge, at 30 days, at 6 months, at 1 year, and then annually through 5 years. All echocardiograms were analyzed by a core laboratory using standard hemodynamic measures. Valve durability was assessed using the Valve Academic Research Consortium 3 (VARC-3) definition of bioprosthetic-valve failure. This definition includes valve reintervention, valve-related death, or deterioration in valve function between the 30-day and follow-up echocardiograms. A group of three experts reviewed all potential cases of valve failure. A clinical events committee independently reviewed and confirmed key five-year outcomes, including all components of the primary endpoints, valve thrombosis (blood clots on the valve), and valve reintervention. ## Who Participated in the Study A total of 1,000 patients underwent randomization. Of these, 503 patients were assigned to TAVR and 497 to surgery. The as-treated population included 496 patients in the TAVR group and 454 in the surgery group. A total of 948 patients (495 in the TAVR group and 453 in the surgery group) received the intended valve. Patients were eligible if they had severe, symptomatic aortic stenosis and were considered at low surgical risk. Low risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score of less than 4%. The STS-PROM estimates the risk of death within 30 days after surgery, with scores ranging from 0 to 100% and higher scores indicating greater risk. The mean age of patients was 73 years, and 69.3% were men. The mean STS-PROM score was 1.9%, confirming that this was a low-risk population. Follow-up data through five years were available for 91.6% of patients overall. However, there was a disproportionate loss to follow-up in the surgery group. Follow-up data were available for 469 of 496 patients (94.6%) in the TAVR group and 401 of 454 patients (88.3%) in the surgery group. A vital-status sweep was conducted to determine the status of patients who had been lost to follow-up or had withdrawn. This sweep yielded data for 66 of 95 patients who had been lost or withdrawn (21 in the TAVR group and 45 in the surgery group). As a result, vital status could be determined for 486 of 496 patients (98.0%) in the TAVR group and 441 of 454 patients (97.1%) in the surgery group. ## What the Researchers Measured The study had two primary endpoints. The first primary endpoint was a composite (combined) measure of death from any cause, stroke, or rehospitalization related to the valve, the procedure, or heart failure. This was analyzed as a time-to-first-event measure. Because some patients had more than one event or more than one rehospitalization over the five-year period, the researchers also prespecified a second primary endpoint. This was a hierarchical composite that included death from any cause, disabling stroke, nondisabling stroke, and the number of rehospitalization days. This endpoint was analyzed using a win ratio method, which compares outcomes between the two groups in a ranked fashion. Secondary endpoints at five years included: - Death or disabling stroke - New-onset atrial fibrillation (a heart rhythm disorder) - Aortic-valve reintervention (a second procedure on the valve) - Endocarditis (infection of the heart valve) - Clinically significant valve thrombosis (blood clots on the valve that affect function) Other secondary endpoints included functional status and quality of life, assessed with the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS). KCCQ-OS scores range from 0 to 100, with higher scores indicating better health status. The researchers also assessed the rate of patients who were alive with a KCCQ-OS score of 75 or higher, which indicated being alive and well. ## Key Findings at Five Years The first primary endpoint — the combined rate of death, stroke, or rehospitalization — occurred in 111 of 496 patients in the TAVR group and 117 of 454 patients in the surgery group. The Kaplan-Meier estimates (a statistical method for estimating event rates over time) were 22.8% in the TAVR group and 27.2% in the surgery group. The difference between the groups was −4.3 percentage points (95% confidence interval [CI], −9.9 to 1.3; P=0.07). The hazard ratio was 0.79 (95% CI, 0.61 to 1.02). Because the P value was 0.07, the difference did not reach the threshold for statistical significance, which is typically set at P less than 0.05. This means the researchers could not conclude that TAVR was definitively superior to surgery for this combined endpoint at five years. These findings appeared to be consistent across all major subgroups of patients. For the second primary endpoint — the hierarchical composite that included death, disabling stroke, nondisabling stroke, and rehospitalization days — the win ratio was 1.17 (95% CI, 0.90 to 1.51; P=0.25). A win ratio of 1.17 means that TAVR "won" 22.1% of patient-pair comparisons versus 19.0% for surgery. However, this difference was not statistically significant. When the researchers looked at the individual components of the first primary endpoint at five years, the results were as follows: - **Death from any cause:** 10.0% in the TAVR group and 8.2% in the surgery group (odds ratio, 1.24; 95% CI, 0.79 to 1.97) - **Stroke:** 5.8% in the TAVR group and 6.4% in the surgery group (hazard ratio, 0.87; 95% CI, 0.51 to 1.48) - **Rehospitalization:** 13.7% in the TAVR group and 17.4% in the surgery group (hazard ratio, 0.75; 95% CI, 0.54 to 1.05) For death from any cause, the odds ratio was calculated. This was because there was evidence that the risk was not proportional over time, meaning the relative risk changed over the five-year period. In a landmark analysis of years 1 to 5, a total of 69 of 453 patients in the TAVR group and 47 of 372 patients in the surgery group had died, had a stroke, or were rehospitalized. These patients had also had a stroke or rehospitalization. The Kaplan-Meier estimates were 15.7% in the TAVR group and 13.7% in the surgery group (hazard ratio, 1.17; 95% CI, 0.81 to 1.70). This suggests that between years 1 and 5, the event rates were similar between the two groups. The restricted mean event-free survival at five years was longer by 103 days (95% CI, 26 to 180) with TAVR than with surgery. This means that, on average, patients who received TAVR lived 103 more days without experiencing death, stroke, or rehospitalization compared with patients who had surgery. ## Valve Function and Durability The hemodynamic performance of the valve — how well blood flows through it — was assessed by measuring the mean valve gradient. The mean (±SD) valve gradient was 12.8±6.5 mm Hg in the TAVR group and 11.7±5.6 mm Hg in the surgery group. These values are similar and indicate good valve function in both groups. Bioprosthetic-valve failure occurred in 3.3% of patients in the TAVR group and 3.8% of patients in the surgery group. This means that about 3 to 4 out of every 100 patients in each group experienced valve failure over five years. Among patients with valve thrombosis (blood clots on the valve), hemodynamic valve deterioration was absent (stage 1) in 4 patients, moderate (stage 2) in 5 patients, and severe (stage 3) in 3 patients. Of the 13 patients with thrombosis, 7 had shortness of breath or dyspnea on exertion, and 3 had a stroke (1 disabling and 2 non-disabling). ## Other Complications and Safety Outcomes The study also tracked several other important outcomes at five years. These included: - **Death or disabling stroke:** 11.5% in the TAVR group and 9.8% in the surgery group (hazard ratio, 1.17; 95% CI, 0.87 to 1.57) - **Aortic-valve reintervention:** 2.0% in the TAVR group and 2.6% in the surgery group (hazard ratio, 0.77; 95% CI, 0.31 to 1.90) - **Endocarditis:** 1.1% in the TAVR group and 1.5% in the surgery group (hazard ratio, 0.72; 95% CI, 0.22 to 2.35) - **Valve thrombosis:** 2.5% in the TAVR group and 0.2% in the surgery group (hazard ratio, 10.52; 95% CI, 1.37 to 80.93) - **New-onset atrial fibrillation:** 13.7% in the TAVR group and 42.4% in the surgery group (hazard ratio, 0.25; 95% CI, 0.19 to 0.34) - **New pacemaker implantation:** 13.5% in the TAVR group and 10.4% in the surgery group (hazard ratio, 1.33; 95% CI, 0.90 to 1.96) - **Serious bleeding:** 10.2% in the TAVR group and 14.8% in the surgery group (hazard ratio, 0.65; 95% CI, 0.45 to 0.95) - **Myocardial infarction (heart attack):** 2.1% in the TAVR group and 4.4% in the surgery group (hazard ratio, 0.48; 95% CI, 0.22 to 1.05) - **Resuscitation:** 3.7% in the TAVR group and 6.0% in the surgery group (hazard ratio, 0.59; 95% CI, 0.32 to 1.09) - **Percutaneous coronary intervention:** 3.5% in the TAVR group and 4.9% in the surgery group (hazard ratio, 0.69; 95% CI, 0.36 to 1.34) - **Coronary artery bypass grafting:** 0.5% in the TAVR group and 1.1% in the surgery group (hazard ratio, 0.36; 95% CI, 0.07 to 1.85) Notably, new-onset atrial fibrillation was much less common after TAVR (13.7%) than after surgery (42.4%). This difference was statistically significant. Serious bleeding was also less common with TAVR (10.2%) than with surgery (14.8%). However, valve thrombosis was more common after TAVR (2.5%) than after surgery (0.2%). This difference was statistically significant, though the number of events was small. ## What These Results Mean for Patients The main finding of this study is that among low-risk patients with severe, symptomatic aortic stenosis, there was no significant difference between TAVR and surgery. This was in the two primary composite outcomes at five years. This means that neither procedure was clearly better than the other for preventing death, stroke, or rehospitalization over this period. However, the results do show some important differences in specific outcomes. TAVR was associated with a lower risk of new-onset atrial fibrillation and serious bleeding. Surgery was associated with a lower risk of valve thrombosis, though this complication was rare in both groups. The finding that TAVR and surgery have similar long-term outcomes is important for patients and their doctors when deciding which procedure to choose. It means that the decision can be based on other factors, such as the patient's anatomy, other medical conditions, and personal preferences. The early advantage of TAVR seen at one and two years — where TAVR had significantly lower rates of the combined endpoint — appeared to narrow over time. By five years, the difference was no longer statistically significant. This suggests that some of the early benefit of TAVR may be offset by later events. The restricted mean event-free survival difference of 103 days favoring TAVR means that, on average, patients who received TAVR spent about three and a half more months without a major event. This was compared with patients who had surgery. This is a meaningful difference for patients, even if the overall statistical test did not reach significance. ## Limitations of the Study There was a disproportionate loss to follow-up in the surgery group. Follow-up data were available for 94.6% of TAVR patients but only 88.3% of surgery patients. This difference could affect the results, although the researchers conducted a vital-status sweep to determine the status of as many patients as possible. The widths of the confidence intervals for continuous and categorical variables were not adjusted for multiple comparisons. This means that the results for individual secondary endpoints should be interpreted with caution, and they should not be used to infer definitive treatment effects. The study was funded by Edwards Lifesciences, the maker of the SAPIEN 3 valve. While the trial leadership had unrestricted access to all data and prepared all drafts of the manuscript, the sponsor's involvement in the trial should be considered when interpreting the results. The study only included patients at low surgical risk, so the results may not apply to patients at intermediate or high risk. The mean age of patients was 73 years, so the results may not apply to younger or older patients. The trial only evaluated the SAPIEN 3 valve. Results may differ with other types of TAVR valves. ## Recommendations for Patients If you have severe, symptomatic aortic stenosis and are considering treatment options, here are some key points to discuss with your heart team: 1. **Both TAVR and surgery are reasonable options.** At five years, the overall outcomes were similar between the two procedures in low-risk patients. 1. **Consider your specific risk profile.** Surgery may be preferred if you have anatomy that makes TAVR difficult or if you have other conditions that favor surgery. 1. **Discuss the trade-offs.** TAVR has a lower risk of atrial fibrillation and serious bleeding but a higher risk of valve thrombosis. Surgery has a lower risk of valve thrombosis but a higher risk of atrial fibrillation and bleeding. 1. **Ask about long-term follow-up.** Both procedures require regular follow-up to monitor valve function and detect any complications early. 1. **Consider your quality of life.** The study assessed quality of life using the KCCQ-OS, and both groups showed improvement. Discuss with your doctor which procedure is likely to give you the best quality of life based on your individual circumstances. 1. **Seek a heart team evaluation.** The decision between TAVR and surgery should be made by a multidisciplinary heart team that includes interventional cardiologists, cardiac surgeons, and other specialists. Remember that this study reports average results for a large group of patients. Your individual experience may differ based on your age, other medical conditions, and the specific characteristics of your heart and valves. ## Frequently Asked Questions ### I have severe aortic stenosis and my doctor says I'm low risk for surgery. What treatment options do I have? In a randomized trial of 1,000 low-risk patients with severe, symptomatic aortic stenosis, two options were compared: transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. At five years, the combined rate of death, stroke, or rehospitalization was similar between the groups. Both procedures are reasonable options, and the choice should be made with a heart team. ### What does it mean that the difference between TAVR and surgery was not statistically significant? It means the researchers could not conclude that one procedure was clearly better than the other for the combined endpoint of death, stroke, or rehospitalization at five years. The rate was 22.8% with TAVR and 27.2% with surgery, but the P value was 0.07, above the usual threshold of 0.05 for statistical significance. ### What are the main risks or complications of TAVR compared with surgery? In the trial, TAVR was linked to a higher rate of valve thrombosis (2.5% vs 0.2% with surgery) but a much lower rate of new-onset atrial fibrillation (13.7% vs 42.4%) and serious bleeding (10.2% vs 14.8%). Death or disabling stroke occurred in 11.5% with TAVR and 9.8% with surgery, a difference that was not statistically significant. ### How long do the replacement valves last, and what is the chance of valve failure? In this trial, bioprosthetic-valve failure occurred in about 3 to 4 out of every 100 patients in each group over five years (3.3% with TAVR and 3.8% with surgery). Valve function remained good in both groups, with similar mean valve gradients. Regular follow-up is still needed to monitor valve function and detect any problems early. ### What does the 103-day difference in event-free survival mean for me? It means that, on average, patients who received TAVR lived 103 more days without death, stroke, or rehospitalization compared with patients who had surgery. This difference is meaningful for patients, even though the overall statistical test for the combined endpoint did not reach significance. Individual experiences may vary based on age, other conditions, and heart anatomy. ### Who should be on my heart team, and what should we discuss when choosing between TAVR and surgery? The decision should be made by a multidisciplinary heart team including interventional cardiologists, cardiac surgeons, and other specialists. Discuss your specific risk profile, the trade-offs between the procedures, long-term follow-up, and quality of life. ### Does this trial's result apply to me if I am younger or older than the average patient? The trial included patients with a mean age of 73 years who were at low surgical risk, so the results may not apply to younger or older patients, or to those at intermediate or high risk. The trial only evaluated the SAPIEN 3 valve, so results may differ with other TAVR valves. Discuss your individual situation with your heart team. ### I have severe aortic stenosis and low surgical risk — should I get a second opinion before choosing TAVR or surgery? At five years, TAVR and surgery produced similar combined rates of death, stroke, or rehospitalization (22.8% versus 27.2%), a difference that was not statistically significant. TAVR carried less new-onset atrial fibrillation (13.7% versus 42.4%) and less serious bleeding (10.2% versus 14.8%), while surgery carried less valve thrombosis (0.2% versus 2.5%). Because neither procedure was clearly better overall, the choice can rest on your anatomy, other conditions, and preferences — a reasonable point to have your imaging and records independently reviewed. Diagnostic Detectives Network provides independent expert second opinions. ## Source Information **Original article title:** Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years NEJM 2023 **Authors:** M.J. Mack, M.B. Leon, V.H. Thourani, P. Pibarot, R.T. Hahn, P. Genereux, S.K. Kodali, S.R. Kapadia, D.J. Cohen, S.J. Pocock, M. Lu, R. White, M. Szerlip, J. Ternacle, S.C. Malaisrie, H.C. Herrmann, W.Y. Szeto, M.J. Russo, V. Babaliaros, C.R. Smith, P. Blanke, J.G. Webb, and R. Makkar, for the PARTNER 3 Investigators **Publication:** New England Journal of Medicine, 2023;389:1949-60 **DOI:** 10.1056/NEJMoa2307447 **Funding:** Edwards Lifesciences **ClinicalTrials.gov number:** NCT02675114 *This patient-friendly article is based on peer-reviewed research.* --- Publisher: Diagnostic Detectives Network (https://diagnosticdetectives.com) — independent multi-expert medical second opinions, worldwide, private-pay. Author byline: Anton Titov, MD, PhD. Contact: https://diagnosticdetectives.com/pages/contact Canonical page: https://diagnosticdetectives.com/products/tavr-vs-surgery-for-aortic-valve-replacement-five-year-results-in-low-risk-patients