In late December 2018, the European HTA agency, EUnetHTA, published the final report of the project OTCA06 - “Transcatheter aortic valve implantation (TAVI) in patients at intermediate surgical risk.”
This project was executed by the Italian National HTA body (AGENAS), with the co-author being the Norwegian Institute for Public Health (NIPH). The dedicated reviewers are KCE from Belgium, Onassis Cardiac Surgery Centre (Greece), Irish HIQA, Swiss National HTA body (SNHTA) and the HTA unit of the Region of Veneto.
The research question was to compare the safety and effectiveness outcomes of TAVI and of traditional open-heart surgery (i.e., surgical aortic valve replacement, SAVR). The HTA Core Model Application for Rapid Relative Effectiveness Assessments (REA, v 4.2) will be followed for the selection of assessment elements.
A search for systematic reviews (SRs) and health technology assessment (HTA) reports published in 2013 or later was performed, followed by a search for RCTs published in 2016 or later. The following sources of information were used: Cochrane Library, Centre for Research and Dissemination (CRD), Embase, and Medline. To identify studies of ‘real-world data’ from prospective national registries, a search for publications from 2013 and later was performed on 5th September 2017, on the following websites: Cochrane Library, Embase, and Medline. To describe upcoming evidence, relevant RCTs registered in 2016 and later were identified by searching the following information sources on 12th January 2018: International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov. The quality of the body of evidence collected was evaluated with The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Eventually, 56 systematic reviews, 1 HTA and 3 records from 2 RCTs have been included in this publication.
Results – clinical effectiveness
- TAVI is probably non-inferior to SAVR in terms of mortality at 30-day follow-up [3.1% versus 2.9%, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.74–1.55; GRADE evidence: moderate]
- There is uncertainty whether TAVI is non-inferior to SAVR in terms of mortality at 2-year follow-up (12.9% versus 12.7%, RR 1.01, 95% CI 0.86–1.20; GRADE evidence: very low)
- TAVI is probably non-inferior to SAVR in terms of cardiac mortality at 30-day follow-up (2.6% versus 2.4%, RR 1.11 95% CI 0.75–1.66; GRADE evidence: moderate)
- There is uncertainty whether TAVI is non-inferior to SAVR in terms of cardiac mortality at 2-year follow-up (12.9% versus 12.7%, RR 1.01, 95% CI 0.86–1.20; GRADE evidence very low)
- TAVI might increase the risk of aortic valve reintervention at 30-day follow-up compared with SAVR (0.6% versus 0.1%, RR 7.58, 95% CI 1.38–41.55; GRADE evidence: low). But, there is uncertainty whether TAVI increases the risk of aortic valve reintervention at 2-year follow-up (1.7% versus 0.4%, RR 3.86, 95% CI 1.76–8.44; GRADE evidence very low)
- There is uncertainty whether TAVI has any effect on improving symptoms compared with SAVR at 1- and 2-year follow-up (data could not be pooled. GRADE evidence: very low)
- The authors are moderately confident that TAVI probably reduces the length of hospital stay by 2 or 3 days compared with SAVR (data not pooled. GRADE evidence: moderate)
Results – safety
- There is uncertainty whether TAVI (compared with SAVR) has any effect on stroke at 30-day follow-up (4.4% versus 5.6%, RR 0.80, 95% CI 0.58–1.10; GRADE evidence: very low) and at 2-year follow-up (7.4% versus 7.6%, RR 0.97, 95% CI 0.74–1.26; GRADE evidence: very low)
- The authors are moderately confident that TAVI probably reduces the incidence of new atrial fibrillation compared with SAVR (11% versus 34%, RR 0.32, 95% CI 0.27–0.37; GRADE evidence: moderate)
- There is uncertainty whether TAVI has any effect on life-threatening or disabling bleeding at 30-day follow-up (two studies, data not pooled; GRADE evidence: very low) and 2-year follow-up (one study, RR 1.02, 95% CI 0.74–1.41; GRADE evidence: very low) compared with SAVR
- There is uncertainty whether TAVI reduces the risk of acute kidney injury at 30-day follow-up (1.0% versus 2.2%, RR 0.47, 95% CI 0.27–0.80; GRADE evidence: very low) and 2-year follow-up (2.2% versus 3.5%, RR 1.02, 95% CI 0.74–1.41; GRADE evidence: very low) compared with SAVR
- Data regarding pacemaker implantation at 30-day follow-up were heterogeneous among studies (and the results were not pooled)
- The authors are moderately confident that TAVI probably increases the risk of paravalvular regurgitation compared with SAVR (3.2% versus 0.3%, RR 9.30, 95% CI 4.02–21.48; GRADE evidence moderate)
- In the PARTNER 2 trial, the incidence of endocarditis at 2-year follow-up was 1.2% in the TAVI group and 0.7% in the control group (RR 1.85, 95% CI 0.69–4.99)
- None of the trials evaluated rehospitalization for myocardial infarction (>72 h following TAVI)
- The authors conclude that, compared with SAVR, TAVI might increase the incidence of major vascular complications at 30-day follow-up (6.9% versus 3.1%, RR 3.03, 95% CI 0.79–11.67; GRADE evidence: low)
There are two ongoing RCTs which are relevant to the scope. Those are The SURTAVI trial (NCT01586910; results expected in November 2026) and the German trial (NCT03112980; results expected in 2023)
The authors conclude that the effectiveness of TAVI for patients with severe aortic stenosis at intermediate surgical risk is probably non-inferior to SAVR in terms of all-cause mortality and cardiac mortality at 30-day follow-up, but also that TAVI probably reduces the length of hospital stay compared with SAVR. More studies are required to make conclusions about whether TAVI is better or worse than SAVR in terms of symptom improvement.
Regarding safety, the authors conclude that, compared with SAVR, TAVI probably reduces new-onset atrial fibrillation and to enhance the risk of paravalvular regurgitation. More studies are required to make conclusions about remaining uncertainties, which regard the evidence on the following outcomes: stroke, acute kidney injury, new permanent pacemaker, major vascular complications, aortic valve reintervention, and life-threatening and/or disabling bleeding.
See the whole assessment in English here.
EUnetHTA also published the experts’ comments, which can be found here.
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