In a blog for health professionals, Dr Ven Gee LIM, Cardiology Registrar reviews the latest Cochrane Systematic Review on ‘Transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis in people with low surgical risk’ by Kolkailah et al [1].
A brief history summarising the developments in the treatment of severe aortic valve stenosis
Aortic valve stenosis (AS) is characterised by narrowing of the aortic valve and usually diagnosed and graded (mild, moderate or severe) with echocardiography. It is the most common heart valve diseas [2] and if severe AS is left untreated, the mortality rate at one year approaches almost 50% [3]. The definitive treatment of symptomatic severe AS is aortic valve replacement (AVR) and surgical AVR (SAVR) has historically been the standard of care as recommended by the international guidelines [4,5]. When I was a medical student, this was certainly the standard practice in the management of severe AS but throughout my training, I have witnessed the development and rapid progress in the alternative treatment to SAVR: Transcatheter aortic valve implantation (TAVI). Instead of open-heart surgery in the SAVR approach, TAVI can be performed in a less invasive manner; the standard approach being the femoral artery6 but alternative access sites such as the subclavian artery, carotid artery, apex of the heart and the aorta may be employed [7]. With a more minimally invasive technique available to replace the stenosed aortic valve, does the advent of TAVI spell the end of SAVR?
The first TAVI in humans was performed by Professor Alain Cribier in Rouen, France on the 16th April 2002 [8]. The patient was a 57-year old man who had calcific AS, cardiogenic shock, subacute leg ischaemia and other significant comorbidities. As several cardiac surgical teams declined his case, the percutaneous heart valve was performed as a “last-resort” case. Under sedation and local anaesthesia, the implantation of the heart valve was performed via the antegrade transseptal approach [i.e right femoral vein -> right atrium -> left atrium (via the interatrial septum) -> left ventricle -> aortic valve]. The valve consisted of 3 bovine pericardial leaflets mounted within a balloon-expandable stent. The procedure resulted in significant clinical and echocardiographic improvements and the rest, as they say, is history.
The different levels of surgical risk
As a Cardiology Registrar, I am regularly involved in referring my symptomatic severe AS patients for discussion at the multi-disciplinary team (MDT) meeting which at the very minimum would consist of the Cardiothoracic surgeons and TAVI team. The crux of the discussion would center on the surgical risk of the patient as that will help inform the choice between SAVR and TAVI.
The three categories of surgical risk (high, intermediate, low) are commonly used in practice and research and are based on a risk model developed by the Society of Thoracic Surgeons (STS) to estimate the risk of death at 30 days post-surgery [9]. The STS risk score in TAVI trials classified high-risk as above 8%, intermediate-risk as 4-8% and low-risk as less than 4%.
At present, TAVI is considered a safe and effective therapy for severe AS patients with high surgical risk as demonstrated by landmark clinical trials; in particular from the PARTNER investigators who conducted a series of studies including PARTNER A (TAVI vs SAVR) and PARTNER B (TAVI vs medical therapy) [10]. However, 75% of severe AS patients fall in the low to intermediate risk categories and TAVI has been used in those groups of patients despite the relative lack of evidence supporting its use [11]. The PARTNER 2 study was a multicenter randomised controlled trial of 2032 patients designed to compare TAVI with SAVR in intermediate-risk patients (4-8%) [12]. In brief, TAVI was non-inferior to SAVR in terms of the primary end points of mortality or disabling stroke at 2 years. The SURTAVI study (a multicenter randomised controlled trial of 1746 patients) also demonstrated non-inferiority of TAVI compared to SAVR at 2 years [13].
The findings of the trials in high-risk and intermediate-risk patients with severe AS have unsurprisingly raised the next important question: Can the use of TAVI be extended to even the severe AS patients who are at low surgical risk?
TAVI trials in low surgical risk patients in 2019
Two landmark trials were published in 2019, which sought to compare TAVI versus SAVR in patients with severe AS at low surgical risk: PARTNER 3 and EVOLUT.
The PARTNER 3 trial randomised 1000 patients with low surgical risk (1.9% in both arms) to either TAVI or SAVR. The TAVI valve used was the balloon-expandable SAPIEN 3 system (Edwards Lifesciences) implanted via the transfemoral route. The trial showed a significant reduction in the primary composite endpoint (death, stroke, rehospitalisation) at 1 year in the TAVI arm (hazard ratio 0.54; 95% CI, 0.37-0.79; p=0.001 for superiority [14].
The EVOLUT trial randomised 1468 patients with low surgical risk (1.9% in both arms) into either TAVI or SAVR [15]. Unlike PARTNER 3, the TAVI valve used was a self-expanding supraannular bioprosthesis (either CoreValve, Evolut R or Evolut PRO; Medtronic). The trial showed that TAVI was non-inferior to SAVR with respect to the composite endpoint of mortality or disabling stroke at 2 years.
What are the main findings of the Cochrane Systematic review?
The Cochrane Systematic review by Kolkailah et al [1] could not have come at a better time. The purpose of their systematic review was to assess the effects of TAVI versus SAVR in severe AS patients with low surgical risk. Four studies including PARTNER 3 and EVOLUT (the other smaller trials were NOTION [16] and STACCATO [17]) were included in the final analysis with 2818 participants. The authors mainly focused on short-term (30 day follow up) hard clinical endpoints. The main findings were:
1) There is probably little or no difference between TAVI and SAVR for the following short-term (30 days) outcomes:
- All-cause mortality [risk ratio (RR) 0.69, 95% Confidence Interval (CI) 0.33-1.44; 4 trials; moderate-certainty evidence]
- Stroke (RR 0.73, 95% CI 0.42-1.25; 4 trials; moderate-certainty evidence)
- Myocardial infarction (RR 0.82, 95% CI 0.42-1.58; 3 trials; moderate-certainty evidence)
- Cardiac mortality (RR 0.71, 95% CI 0.32-1.56; 4 trials; moderate-certainty evidence)
2) TAVI may reduce the risk of short-term rehospitalisation (RR 0.64, 95% CI 0.39-1.06; 2 trials; low-certainty evidence)
3) TAVI probably increases the risk of pacemaker implantation (RR 3.65, 95% CI 1.50-8.87; number needed to treat for additional harmful outcome (NNTH) 7; 3 trials; moderate-certainty evidence)
4) TAVI reduces the risk of:
- Atrial fibrillation (RR 0.21, 95% CI 0.15-0.30; 3 trials; high-certainty evidence)
- Acute kidney injury (RR 0.30, 95% CI 0.16-0.58; 4 trials; high-certainty evidence)
- Bleeding (RR 0.31, 95% CI 0.16-0.62; 4 trials; high-certainty evidence)
Limitations
As with all novel techniques, data on the durability of the TAVI valve is required. Furthermore, the low surgical risk patient population is usually younger with a longer life expectancy. As the majority of patients in the systematic review came from the PARTNER 3 and EVOLUT trials, the duration of follow-up was limited to one to two years. Therefore, long-term clinical and echocardiographic follow up is needed to assess the longer-term benefits and harms and this is planned in both PARTNER 3 and EVOLUT over a 10 year period.
In addition, the trials excluded patients with bicuspid aortic valves who are probably under-represented in younger low surgical risk patients with AS. In addition, it is also recognised that TAVI is technically more challenging in bicuspid aortic valves compared to tricuspid aortic valves thus its utility in this group of patients remains limited at present [18]. Given the aforementioned limitations of TAVI especially in low surgical risk patients, in my view, the role of SAVR in the management of severe AS remains crucial.
Where does this leave us?
In the past decade, the Cardiology and Cardiothoracic surgical community has witnessed the birth and evolution of a novel therapy for severe aortic stenosis. In my opinion, the Cochrane Systematic Review by Kolkailah et al has demonstrated the potential utility of TAVI in low surgical patients with severe AS in the short term. Only time will tell if the benefits of TAVI in this group of patients will be sustained in the long run. Nevertheless, I am optimistic that as the technology improves during this decade, the benefits of TAVI will probably extend to groups of patients that we will not have thought possible at this present day. In my clinical opinion, there is still a role for SAVR at present and TAVI should not be seen as a replacement to SAVR but an additional treatment option for patients with severe AS.
Take home points
- TAVI is considered a safe and effective therapy for severe AS patients with high surgical risk and its use in intermediate-risk patients is non-inferior to SAVR.
- There is probably little or no difference in TAVI compared to SAVR in severe AS patients with low surgical risk in terms of short-term outcomes for: mortality (all-cause and cardiovascular), stroke and myocardial infarction.
- Compared with SAVR, TAVI in low-risk patients may reduce short-term rehospitalisation.
- TAVI also reduces the risk of atrial fibrillation, acute kidney injury and bleeding but probably at the expense of an increased risk of pacemaker implantation compared with SAVR.
Ven Gee Lim @v3n_3
Ven is currently a Clinical Lecturer at the University Hospitals Coventry and Warwickshire NHS Trust and a post-doc research fellow at the University of Warwick. He completed his Cardiology training at the West Midlands Deanery with a subspecialty interest in Electrophysiology and Devices.
Ven graduated from the University of Edinburgh (Honours) in 2009, obtained his MRCP in 2012 and completed his Masters in Internal Medicine (Distinction) at his alma mater in 2014. He then pursued a PhD in Cardiovascular Science at University College London (out-of-programme research) where the focus of his research was on the role of SGLT2 inhibitors in cardioprotection and graduated in 2021.
Ven Gee Lim has no conflicts of interest to declare.
Posted: January 2020.