Highlights
The sex-specific analysis of the DEDICATE-DZHK6 trial provides critical insights into the management of aortic stenosis in low- to intermediate-risk patients. Key highlights include:
- TAVI demonstrated significantly lower rates of all-cause death or stroke at one year compared to SAVR in both women and men.
- Women assigned to SAVR experienced a notably higher risk of stroke (6.2%) compared to those receiving TAVI (2.6%).
- Despite being older and having higher surgical risk scores at baseline, women derived a substantial survival benefit from the transcatheter approach.
- The trial reaffirms TAVI as a preferred or equally viable strategy for both sexes in the low-to-intermediate risk category, challenging traditional surgical-first paradigms.
Introduction: The Clinical Imperative for Sex-Specific Data
For decades, the management of severe symptomatic aortic stenosis (AS) was dictated by data predominantly derived from male-heavy cohorts. However, physiological and anatomical differences between men and women—ranging from aortic root dimensions to the prevalence of concentric hypertrophy—suggest that a one-size-fits-all approach to valve replacement may be suboptimal. While transcatheter aortic valve implantation (TAVI) has revolutionized the field, the question of whether sex should influence the choice between TAVI and surgical aortic valve replacement (SAVR) in lower-risk populations has remained a subject of intense debate.
The DEDICATE-DZHK6 trial was designed to address these gaps by evaluating TAVI versus SAVR in a contemporary European cohort. This predefined subgroup analysis specifically investigates whether the benefits of TAVI are consistent across sexes or if one group derives a unique advantage from a specific modality.
Study Design: The DEDICATE-DZHK6 Framework
The DEDICATE-DZHK6 trial was a multicenter, randomized, non-inferiority trial conducted across Germany. It enrolled patients with severe symptomatic aortic stenosis who were at low to intermediate surgical risk. A total of 1,394 patients were randomized to either TAVI (using commercially available balloon-expandable or self-expanding valves) or SAVR.
Population and Endpoints
The study population was 43.3% female. The primary outcome was a composite of all-cause mortality or stroke at one year post-procedure. Secondary endpoints included individual components of the primary outcome, procedural complications, and hemodynamic performance of the valves. Unlike many early TAVI trials, DEDICATE-DZHK6 focused on a ‘real-world’ low-to-intermediate risk population, making the findings highly applicable to current clinical practice.
Participant Characteristics: A Risk Profile Divergence
The baseline data revealed significant differences between the sexes. Women in the trial were, on average, older than their male counterparts (74.8 years vs. 74.2 years, P = .020). Furthermore, women presented with a higher median Society of Thoracic Surgeons (STS) risk score (2.1% vs. 1.5%, P < .001). This higher baseline risk in women is a common finding in AS trials, often attributed to later presentation or different comorbidity profiles, such as smaller body surface area and higher prevalence of frailty.
Key Findings: Breaking Down the Data by Sex
The primary composite endpoint of all-cause death or stroke at one year showed a consistent advantage for TAVI over SAVR across both sexes, though the magnitude of effect was particularly striking in women.
Outcomes in Women
In the female cohort, the primary outcome occurred in 5.2% of the TAVI group compared to 11.5% in the SAVR group. This represents a significant reduction in risk (Hazard Ratio [HR] 0.46; 95% Confidence Interval [CI] 0.25-0.82). When looking at mortality alone, women in the TAVI group had a 2.6% death rate compared to 6.7% in the SAVR group (HR 0.41). Perhaps most importantly, the stroke rate was more than halved in the TAVI group (2.6% vs. 6.2%; HR 0.43).
Outcomes in Men
Among men, TAVI also performed well, with the primary outcome occurring in 5.4% of the TAVI group versus 9.0% in the SAVR group (HR 0.61; 95% CI 0.35-1.03). Mortality was 2.6% for TAVI and 5.9% for SAVR (HR 0.44). However, the difference in stroke rates was less pronounced in men than in women (3.1% for TAVI vs. 3.6% for SAVR; HR 0.89).
Mechanistic Insights: Why TAVI Favors the Female Anatomy
The discrepancy in stroke rates after SAVR between men and women is a critical finding. Experts suggest that several factors may contribute to this. Women often have smaller aortic roots and narrower sinotubular junctions. During surgery, the manipulation of a smaller aorta and the potential need for root enlargement procedures may increase the risk of embolic events or prolonged bypass times, both of which are linked to neurological complications.
Furthermore, TAVI valves—particularly supra-annular designs—often provide superior hemodynamics in small aortic annuli compared to smaller surgical bioprostheses, which are prone to patient-prosthesis mismatch (PPM). PPM is known to be more prevalent in women and is associated with poorer long-term survival and slower regression of left ventricular hypertrophy.
Expert Commentary: Clinical Implications
The results of the DEDICATE-DZHK6 sex-specific analysis suggest that for women at low to intermediate risk, TAVI should not just be considered an alternative to surgery, but perhaps the preferred strategy when anatomical features are favorable. The 11.5% rate of death or stroke at one year for women undergoing SAVR is unexpectedly high for a low-risk cohort and warrants a re-evaluation of surgical risks in this demographic.
However, clinicians must remain cautious. While the one-year data is compelling, long-term durability remains the ‘final frontier’ for TAVI. Younger women with long life expectancies may still require a nuanced discussion regarding the lifetime management of valve disease, including the feasibility of future valve-in-valve procedures versus the initial durability of a surgical valve.
Conclusion: Redefining the Standard of Care
The DEDICATE-DZHK6 trial reinforces the safety and efficacy of TAVI in both sexes but highlights a specific opportunity to improve outcomes in women. By significantly reducing the incidence of stroke and early mortality compared to SAVR, TAVI addresses some of the historical disadvantages women faced in surgical cohorts. As heart teams continue to refine patient selection, these sex-specific insights will be instrumental in tailoring therapy to ensure the best possible outcomes for all patients with aortic stenosis.
Funding and ClinicalTrials.gov
The DEDICATE-DZHK6 trial was supported by the German Center for Cardiovascular Research (DZHK) and the German Heart Foundation. ClinicalTrials.gov Identifier: NCT03073473.
References
- Bleiziffer S, et al. Sex-specific outcomes after transcatheter or surgical treatment of aortic valve stenosis: the DEDICATE-DZHK6 trial. European Heart Journal. 2026;47(11):1339-1353.
- Mack MJ, et al. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med. 2019;380(18):1695-1705.
- Popma JJ, et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019;380(18):1706-1715.
