Non–vitamin K antagonist versus vitamin K antagonist oral anticoagulant agents after transcatheter aortic valve replacement

Selected in JACC: Cardiovascular Interventions by N. Ryan , A. Gasecka

This study demonstrates that, at 5 years post TAVI in patients with an indication for OAC, the net clinical benefit did not differ between the VKA and DOAC groups.

Reviewers

Nicola Ryan

@NicolaRyanI1

Interventional cardiologist / Cardiologist

Aberdeen Royal Infirmary - Aberdeen, United Kingdom

Aleksandra Gasecka

@aleks_gasecka

Interventional cardiologist / Cardiologist

Medical University of Warsaw - Warszawa, Poland

Our Comment

Using the SwissTAVI registry, the authors compared periprocedural, short and long-term safety and efficacy of direct oral anticoagulant agents (DOACs) and vitamin K antagonists (VKAs) in patients undergoing transcatheter aortic valve replacement (TAVR), with concomitant indications for oral anticoagulation.

Designed by Aleksandra Gąsecka and Nicola Ryan

Designed by Aleksandra Gąsecka and Nicola Ryan

Why this study – the rationale/objective?

Up to 50 % of patients undergoing TAVI have concomitant indications for long-term oral anticoagulation (OAC) therapy. In many clinical scenarios, DOACs are preferred over VKAs due to an improved risk-benefit profile compared with VKAs.

DOACs are typically less onerous for patients with fixed dosing, fewer drug interactions, and a reduced requirement for monitoring. Therefore, the use of DOACs following TAVI is attractive, however, studies comparing outcomes in patients treated with DOACs and VKAs post TAVR are small, with conflicting results.

In this study, the authors used a national prospective, multicentre, registry (SwissTAVI) to compare the safety and efficacy of DOACs and VKAs in patients undergoing TAVR discharged on OAC.

How was it executed – the methodology?

Consecutive patients undergoing transfemoral TAVR at 15 centres in Switzerland enrolled in the SwissTAVI Registry between February 2011 and June 2021 were included in the analysis. In patients with an indication for OAC, VKAs or DOACs, at the discretion of the treating heart team, were used alone or in combination with one or two antiplatelet agents, as recommended by guidelines at the time of enrolment.

Endpoints were recorded at 30 days, 1 year, and 5 years after TAVR and adjudicated by a dedicated committee, blinded for patient data. To account for baseline difference between the groups, propensity score matching in a 1:1 ratio was performed prior to analysis. Considering the gradual increase in DOAC-to-VKA prescription ratio over time, expansion of TAVR to lower risk patients and decrease in the concomitant use of antiplatelet therapy throughout the follow-up period, hazard ratios (HR) were adjusted for Society of Thoracic Surgeons (STS) score, the year of TAVR and antiplatelet therapy regimen,

• The net clinical benefit was defined as a composite of all-cause mortality, myocardial infarction, stroke and life-threatening or major bleeding;
• The primary safety endpoint was a composite of life-threatening and major bleeding;
• Secondary outcomes included a composite of all-cause mortality, stroke and myocardial infarction, a composite of nonprocedural life-threatening bleeding and major bleeding, all-cause mortality and stroke.

What is the main result?

After 1:1 propensity score matching, 1,454 patients per group were available for analysis. The mean age was 82 years and 53 % of patients were male. All patients were well matched, except for a lower left ventricular ejection fraction (52.8 ± 14.5 % vs. 54.6 ± 13.6 %) and higher STS score (5.5 ± 4.3 % vs. 4.7 ± 3.4 %) in patients treated with VKA’s. There were no differences in antithrombotic regimens, prosthetic type and post procedure moderate to severe valvular regurgitation between the groups.

The rates of net clinical benefit and primary safety endpoint were comparable between VKAs and DOACs at:

• 30 days (14.4 % vs. 14.0 %, adjHR 1.01, 95 % CI 0.79-1.30, p = 0.93)
• 1 year (27.8 % vs. 25.9 %, adjHR 1.05, 95 % CI 0.88-1.24, p = 0.61)
• 5 years (68.9 % vs. 62.8 %, adjHR 1.1, 95 % CI 1.0-1.22, p = 0.062).

Higher all-cause mortality at 1 year (14.8 % vs. 11.2 %, HR 1.28; 95 % CI 1.01-1.62, p = 0.038) and 5-years (HR 1.25; 95 % CI 1.11-1.40) was observed in the VKA group.

After excluding periprocedural events (0-30 days), the risk for disabling stroke was lower in the VKA group (3.1 % vs. 5.7 %, HR 0.64; 95 % CI 0.46-0.90, p = 0.01).

Critical reading and the relevance for clinical practice

Designed by Aleksandra Gąsecka and Nicola Ryan

Designed by Aleksandra Gąsecka and Nicola Ryan

This study demonstrates that at 5 years post TAVI in patients with an indication for OAC, the net clinical benefit did not differ between the VKA and DOAC groups. In this real world registry data, VKAs were associated with a higher risk of all-cause mortality and a lower risk for disabling stroke.

The results of SwissTAVI study are concordant with the results of two other registry-based studies (France-TAVR + FRANCE¹ and STS/ACC TVT²), demonstrating that VKA post TAVR is associated with a higher rate of 1- to 3-year mortality, compared to DOACs.

The observed increased bleeding rate with VKAs in these registries was not observed in the SwissTAVI registry. Randomised trials of DOACs and VKA (ENVISAGE-TAVI AF³ and ATLANTIS⁴) both show similar mortality rates with DOACs and VKA, with increased bleeding in the ENVISAGE-TAVI AF trial in the VKA arm.

Despite propensity-score matching, patients discharged on VKA had lower left ventricular ejection fraction and a higher STS score, indicating a worse prognosis, therefore the higher VKA-associated mortality in the SwissTAVI study may simply be due to a higher baseline risk.

The landmark analysis demonstrating a higher risk of disabling stroke on DOACs compared to VKAs from 30 days to 5 years is an important consideration, particularly as TAVI expands to lower-risk patients, with a longer life expectancy. The optimal anticoagulation regimen must take into account the ischaemic and bleeding risks, patient compliance and preference, as well as the impact of adverse events on the patients quality of life. The patients included in this registry data were compliant with VKA therapy and monitoring, which is an important consideration when individualising treatment.

Compared to previous studies, the contemporary clinical landscape of TAVI encompasses lower-risk patients treated with new-generation bioprosthetic valves and receive mostly DOACs, if oral anticoagulation is required, with no concomitant antiplatelet therapy. The unique features of TAVI population include (i) a potentially increased thromboembolic risk due to subclinical bioprosthetic valve thrombosis, which might be a risk for clinical stroke, and (ii) a potentially increased bleeding risk due to the high prevalence of gastrointestinal angiodysplasia and acquired von Willebrand syndrome.

The rapidly evolving clinical landscape along with the unique risk-to-benefit profile of contemporary TAVR patients warrants a dedicated, randomized controlled trial to set the optimal post-TAVR OAC regimen. Until then, no firm conclusions regarding the superiority of VKAs or DOACs after TAVI.

References

1. Didier R, Lhermusier T, Auffret V, Eltchaninoff H, Le BH, Cayla G, et al. TAVR Patients Requiring Anticoagulation. JACC: Cardiovascular Interventions. 2021 Aug 9;14(15):1704–13.
2. Tanawuttiwat T, Stebbins A, Marquis-Gravel G, Vemulapalli S, Kosinski AS, Cheng A. Use of Direct Oral Anticoagulant and Outcomes in Patients With Atrial Fibrillation after Transcatheter Aortic Valve Replacement: Insights From the STS/ACC TVT Registry. J Am Heart Assoc. 2022 Jan 4;11(1):e023561.
3. Van Mieghem NM, Unverdorben M, Hengstenberg C, Möllmann H, Mehran R, López-Otero D, et al. Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR. New England Journal of Medicine. 2021 Dec 2;385(23):2150–60.
4. Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial | European Heart Journal | Oxford Academic [Internet]. [cited 2024 Mar 18]. Available from: https://academic.oup.com/eurheartj/article/43/29/2783/6587401