Transcatheter or Surgical Treatment of Aortic-Valve Stenosis — DEDICATE-DZHK6

Authors, Journal, Affiliations, Type, DOI

• Authors: Stefan Blankenberg, Moritz Seiffert, Reinhard Vonthein, et al. for the DEDICATE-DZHK6 Trial Investigators
• Journal: New England Journal of Medicine 2024;390:1572–83
• Affiliations: University Heart and Vascular Center Hamburg (coordinating); 38 German centres including Leipzig, Frankfurt, Munich, Freiburg, Berlin, Kiel, Lübeck, Dresden, Heidelberg, Bad Nauheim
• Type: Investigator-initiated, randomised noninferiority RCT (industry-independent)
• DOI: https://doi.org/10.1056/NEJMoa2400685

Overview

DEDICATE-DZHK6 is the largest industry-independent, pragmatic randomised trial comparing TAVI versus SAVR in 1,414 patients with severe symptomatic aortic stenosis at low or intermediate surgical risk (median STS-PROM 1.8%, mean age 74 years) at 38 German centres. Operators freely selected any CE-marked prosthesis after randomisation. At 1 year, TAVI was noninferior — and strongly directionally superior — to SAVR for the composite of death or stroke (5.4% vs 10.0%; HR 0.53; P<0.001). All-cause mortality was 2.6% vs 6.2% (HR 0.43). The pragmatic, device-unrestricted design makes this the most generalisable comparative TAVI–SAVR trial to date.

Keywords

Aortic stenosis, transcatheter aortic valve implantation, surgical aortic valve replacement, noninferiority, low-risk patients, pragmatic trial, operator discretion, CE-marked devices, Germany

Key Takeaways

Trial Design and Population

• Investigator-initiated, randomised, multicenter, open-label noninferiority trial at 38 German sites; May 2017 – September 2022
• 1:1 randomisation by electronic web-based system; balanced variable blocks; stratified by site and STS-PROM score
• Pragmatic design: all CE-marked devices allowed; TAVI and SAVR prosthesis selection at operator/heart team discretion after randomisation — unrestricted device access not used in prior industry-sponsored RCTs
• Eligibility: age ≥65, severe symptomatic aortic stenosis, low or intermediate surgical risk by clinical assessment, eligible for both TAVI and SAVR
• Exclusions: untreated clinically significant CAD, previous cardiac surgery, bicuspid AV, other VHD requiring surgery
• Mean age 74±4 years; 57% male; median STS-PROM 1.8% (predominantly low surgical risk); baseline characteristics balanced between groups

Procedural Details

• TAVI group: 97.3% transfemoral access; 75.1% conscious sedation or local anesthesia; 61.4% balloon-expandable valve; 35.1% self-expanding; cerebral embolic protection in 5.1%; median procedure time 48 min; ICU 1 day; hospital stay 5 days; 74.7% discharged directly home
• SAVR group: 50.9% full sternotomy; 38.7% partial sternotomy; 77.4% stented bioprosthesis; 15.8% sutureless/rapid-deployment; median procedure 165 min; CPB 88 min; cross-clamp 61 min; ICU 2 days; hospital stay 9 days; 40.4% discharged directly home
• Crossover: 70 SAVR-allocated patients underwent TAVI (mostly patient request); 12 TAVI-allocated patients underwent SAVR
• 70 crossovers represent a trial limitation but as-treated analysis was consistent with ITT

Primary Outcome

• Composite: death from any cause or fatal/nonfatal stroke within 1 year
• TAVI 5.4% vs SAVR 10.0%; HR 0.53 (95% CI 0.35–0.79; P<0.001 for noninferiority)
• Noninferiority margin was HR ≤1.14 (upper CI 0.79 — well below 1.0 and well below noninferiority margin)
• As-treated analysis consistent: 5.6% vs 10.1% (HR 0.54; 95% CI 0.36–0.80)

Secondary Outcomes — Efficacy

• All-cause death: TAVI 2.6% vs SAVR 6.2% (HR 0.43; 95% CI 0.24–0.73) — significant
• Cardiovascular death: 2.0% vs 4.4% (HR 0.47; 95% CI 0.24–0.86) — significant
• Stroke: 2.9% vs 4.7% (HR 0.61; 95% CI 0.35–1.06) — directional, not significant
• Stroke or TIA: 4.1% vs 5.1% (HR 0.78; 95% CI 0.47–1.27) — NS
• Disabling stroke: 1.3% vs 3.1% (HR 0.42; 95% CI 0.19–0.88) — significant
• Death or disabling stroke: 3.8% vs 8.4% (HR 0.45; 95% CI 0.28–0.70) — significant
• New-onset AF: 12.4% vs 30.8% (HR 0.36; 95% CI 0.28–0.46) — significantly lower with TAVI
• Permanent pacemaker implantation: 11.8% vs 6.7% (HR 1.81; 95% CI 1.27–2.61) — significantly higher with TAVI
• Prosthetic-valve dysfunction at 1 year: 1.6% vs 0.6% (HR 2.44; 95% CI 0.87–8.15) — NS trend higher with TAVI
• Aortic-valve reintervention, valve thrombosis, endocarditis, CV rehospitalization: similar in both groups at 1 year

Secondary Outcomes — Safety

• Major or life-threatening bleeding: TAVI 4.3% vs SAVR 17.2% (HR 0.24; 95% CI 0.16–0.35) — dramatically lower with TAVI
• Vascular access-site complications: TAVI 7.9% vs SAVR 0.7% (HR 10.64; 95% CI 4.84–28.94) — significantly higher with TAVI
• AKI stage II/III (within 7 days): 1.3% vs 2.5% (HR 0.56; 95% CI 0.24–1.21) — NS
• Myocardial infarction: 1.0% vs 2.1% (HR 0.51; 95% CI 0.20–1.19) — NS

Valve Hemodynamics at 1 Year

• Mean aortic-valve gradient: 10 mmHg (TAVI) vs 11 mmHg (SAVR) — comparable; both normal
• Mean effective orifice area: 1.6 cm² in both groups
• Aortic regurgitation ≥moderate: 16 patients (2.8%) TAVI vs 5 patients (1.0%) SAVR — higher with TAVI; merits long-term follow-up

Limitations of the Document

• Short follow-up (1 year only): Primary outcome at 5 years pre-specified and planned — crucial for durability and long-term mortality
• COVID-19 pandemic enrollment (majority of patients): SAVR outcomes worse than prior trials; subgroup analyses stratified by COVID-19 lockdown were concordant but confounding cannot be excluded
• Crossover (70 SAVR→TAVI): mostly patient preference; ITT and as-treated results consistent
• Bicuspid AV and concomitant surgery excluded: limits applicability to younger patients with BAV
• Germany only: No race/ethnicity data; generalisability to non-German populations uncertain
• Not consecutive all-comers: patients requesting a specific therapy were excluded; however, no treatment assignment bias vs German Heart Report registry
• VARC-2 criteria used (not VARC-3): most patients enrolled before VARC-3 publication

Key Concepts Mentioned

• concepts/TAVI — primary intervention compared; pragmatic real-world evaluation of device-unrestricted TAVI
• concepts/Aortic-Stenosis — primary disease; low/intermediate surgical risk population
• concepts/Valvular-Heart-Disease — disease category and management context
• concepts/Structural-Valve-Deterioration — valve durability data at 1 year; long-term follow-up needed

Key Entities Mentioned

• None specific beyond trial investigators

Wiki Pages Updated

• wiki/sources/tavr-dedicate-nejm-2024.md — created (this file)
• wiki/sourceindex.md — entry added
• wiki/wikiindex.md — TAVI concept description updated
• wiki/concepts/TAVI.md — DEDICATE-DZHK6 section added; Contradictions updated; source_count 6→7
• wiki/concepts/Aortic-Stenosis.md — TAVI vs SAVR evidence section updated; source_count 8→9