TAVI Clinical Trials: Existing and Ongoing Studies
Ongoing Trials (as of 2008)
The PARTNER US trial is the primary ongoing randomized controlled trial evaluating TAVI, with all-cause mortality at 1 year as the primary endpoint. 1
PARTNER Trial Design
The PARTNER trial employs two distinct study populations with different comparators 1:
- High-risk operable patients: TAVI compared with surgical valve replacement using non-inferiority design for efficacy and superiority design for safety 1
- Non-operable patients: TAVI compared with best available medical treatment using superiority design for efficacy 1
Completed Studies and Registry Data
Transfemoral Approach Results
Over 900 high-risk patients have been treated via transfemoral TAVI (400 with balloon-expandable and 500 with self-expandable prostheses) across multiple centers worldwide, demonstrating feasibility with 90% procedural success in experienced centers. 1
Key Outcomes from Transfemoral Studies 1:
- 30-day mortality: 5-18%
- Final valve area: 1.5-1.8 cm² 1, 2
- Stroke incidence: 3-9% 1, 2
- Vascular complications: 10-15% 1, 2
- Acute myocardial infarction: 2-11% 1
- Paravalvular regurgitation (mild-to-moderate): 50% of cases 1, 2
- Severe aortic regurgitation: Decreased to 5% with larger prostheses and improved sizing 1, 2
- Pacemaker requirement: Up to 24% with self-expandable devices 1, 2
- Prosthesis embolization: 1% 1
Transapical Approach Results
Over 300 high-risk patients with peripheral arterial disease have undergone transapical TAVI, achieving 90% implantation success with 70-90% performed off-pump in experienced centers. 1
Key Outcomes from Transapical Studies 1:
- Mortality: 9-18%
- Stroke incidence: 0-6%
- Conversion rate: 9-12%
Duration of Follow-up
Long-term results up to 2 years are reported in limited patient numbers, demonstrating good short- and medium-term hemodynamic results without structural valve deterioration. 1, 2 Most studies report only 1-year follow-up data 1.
Mandatory Registry Requirements
Regional, national, and international registries are mandatory for TAVI evaluation before general medical community release, with completeness of data essential. 1
Registry Follow-up Requirements 1:
- Pre-market phase: Minimum 1 year safety assessment
- Post-marketing surveillance: Ideally 5 years
- Data collection: All patients referred for TAVI regardless of final treatment strategy
Future Trial Directions
Extension of TAVI to lower-risk patient populations must occur only within randomized trial settings. 1 The European guidelines emphasize that randomized trials are highly desirable once greater experience is acquired and only small modifications in technology are expected 1.
Standardized Endpoints for Future Trials 1:
- All-cause mortality (30-day, in-hospital, 1-year)
- Stroke
- Myocardial infarction
- Re-hospitalization
- Reoperation
- Arrhythmias and conduction disturbances
Critical Safety Concerns Requiring Further Investigation
Four major safety concerns remain under active investigation: 1
- Vascular complications with transfemoral approach (expected to decrease with smaller devices) 1
- Stroke rates, particularly with transfemoral approach 1
- Long-term consequences of paravalvular leaks, even mild-to-moderate regurgitation 1, 2
- Atrioventricular block: incidence, timing, and predictors require precise identification 1, 2
Expanding Indications Under Investigation
TAVI is being explored for bicuspid aortic valve stenosis, asymptomatic severe aortic stenosis, moderate aortic stenosis with heart failure with reduced ejection fraction, and isolated pure aortic regurgitation in ongoing clinical trials. 3 Two randomized trials published in 2019 assessed TAVI in low operative risk patients with symptomatic severe aortic stenosis, demonstrating early safety benefits over surgical replacement with faster hospital discharge and fewer rehospitalizations 3.