Key messages
• In people who do not have a medical reason to take blood thinners, non-vitamin K antagonist oral anticoagulants (NOACs), specifically rivaroxaban and apixaban, may increase the risk of death for any reason when compared with antiplatelet drugs, while edoxaban appears to have little or no effect. Any differences between rivaroxaban, apixaban, or edoxaban, and antiplatelet therapy in death caused by diseases of the heart or blood vessels are likely small. Similarly, differences between rivaroxaban or edoxaban and antiplatelets in stroke are also likely small. In these people, the risk of serious bleeding is probably increased with rivaroxaban; however, there seems to be little or no difference between apixaban and antiplatelet therapy, and we are uncertain about the impact of edoxaban on serious bleeding.
• In people who have a medical reason to take blood thinners, NOACs, specifically apixaban and edoxaban, may be as effective as warfarin in preventing death for any reason, death caused by diseases of the heart or blood vessels, and stroke. While apixaban may lead to a similar rate of serious bleeding as warfarin in these people, edoxaban likely increases the risk of serious bleeding when compared with warfarin.
• We are uncertain if any one type of NOAC is better than another after transcatheter aortic valve replacement (TAVR). More studies are needed directly comparing the effects of different NOACs against each other after TAVR.
What is transcatheter aortic valve replacement (TAVR)?
TAVR is a heart valve replacement procedure that does not require open-heart surgery. It uses a heart catheter to insert a new valve through a small surgical incision in the leg or chest. Choosing the best treatment for people after TAVR remains a challenge in clinical practice.
What did we want to find out?
We looked at whether the next-generation blood thinners, non-vitamin K antagonist oral anticoagulants (NOACs), are safer and more effective than antiplatelet drugs or vitamin K antagonists (VKAs), such as warfarin, after TAVR.
What did we do?
We searched for studies that looked at the benefits and harms of NOACs compared with antiplatelet therapy or VKA after TAVR.
What did we find?
We found five studies that compared three types of NOACs: rivaroxaban, apixaban, and edoxaban, with antiplatelet drugs or warfarin, one of which is ongoing. Our review findings are based on the four completed studies involving 4808 participants.
Main results
We found that in people who did not have a medical reason to take blood thinners, the NOACs rivaroxaban and apixaban may increase the risk of death for any reason compared to antiplatelet therapy, while edoxaban appears to have little or no effect. Any differences between rivaroxaban, apixaban, or edoxaban, and antiplatelet therapy in death caused by diseases of the heart or blood vessels are likely small. Similarly, differences between rivaroxaban or edoxaban and antiplatelets in stroke are also likely small. In these people, the risk of serious bleeding is probably increased with rivaroxaban; however, there seems to be little or no difference between apixaban and antiplatelet therapy, and we are uncertain about the impact of edoxaban on serious bleeding.
In people who have a medical reason to take blood thinners, we found that apixaban and edoxaban may be as effective as warfarin in preventing death for any reason, death caused by diseases of the heart or blood vessels, and stroke. Apixaban may result in a similar rate of serious bleeding as warfarin, whereas edoxaban probably increases the rate of serious bleeding compared to warfarin.
We are uncertain if any one type of NOAC is better than another. More research is needed to know for sure.
What are the limitations of the evidence?
We have little confidence in the evidence for apixaban and edoxaban because the included studies were small. We are only moderately confident in some of the evidence for rivaroxaban, also due to the small size of studies.
How up-to-date is this review?
The evidence is current to October 2023.
In people without an indication for oral anticoagulation, rivaroxaban and apixaban may increase all-cause mortality when compared to antiplatelet therapy, while edoxaban may result in little or no difference. There might be little or no difference between rivaroxaban, apixaban, or edoxaban and antiplatelet therapy in cardiovascular mortality, and between rivaroxaban or edoxaban and antiplatelets in stroke. While rivaroxaban probably increases major bleeding following TAVR, there might be little or no difference between apixaban and antiplatelet therapy, and the effect of edoxaban on major bleeding remains unclear.
In people with an indication for anticoagulation, apixaban and edoxaban may be as effective as VKA in preventing all-cause mortality, cardiovascular death, and stroke. Apixaban may lead to a similar rate of major bleeding as VKA in this population. However, edoxaban probably increases major bleeding following TAVR when compared to VKA.
Our NMA did not show superiority of one NOAC over another for any of the primary outcomes. Head-to-head trials directly comparing NOACs against each other are required to increase the certainty of the evidence.
Balancing the risk of thromboembolism and bleeding after transcatheter aortic valve replacement (TAVR) remains clinically challenging. Questions regarding the efficacy and safety of non‐vitamin K oral anticoagulants (NOACs) after TAVR still need to be definitively answered.
To evaluate the efficacy and safety of NOACs after TAVR in individuals with and without indication for anticoagulation.
We searched CENTRAL, MEDLINE, Embase, Web of Science, ClinicalTrials.gov, and WHO ICTRP on 7 October 2023 together with reference checking and citation searching to identify additional studies.
We searched for randomised controlled trials (RCTs) that compared NOACs versus antiplatelet therapy or vitamin K antagonists (VKAs) after TAVR in adults with or without an indication for anticoagulation.
We used standard Cochrane methods and conducted random-effects pair-wise analyses and network meta-analyses (NMAs). Our primary outcomes were all-cause mortality, cardiovascular mortality, stroke, and major bleeding. We used GRADE to assess the certainty of evidence.
We included four RCTs with 4808 participants in the NMA. Of these, one compared rivaroxaban versus antiplatelet therapy in people without an indication for anticoagulation after TAVR; one compared apixaban versus antiplatelet therapy in people without an indication for anticoagulation or versus VKA in people with an indication for anticoagulation after TAVR; one compared edoxaban versus VKA in people with an indication for anticoagulation after TAVR; and one compared edoxaban with antiplatelet therapy in people without an indication for anticoagulation after TAVR. The mean age of trial participants was 81 years. Follow‐up duration ranged from 6 to 18 months. Overall, we judged the risk of bias in the included trials to be low in all domains except for blinding, which was assessed as high in all four studies. No studies evaluated dabigatran.
In people without an indication for anticoagulation, rivaroxaban and apixaban may increase all-cause mortality after TAVR as compared to antiplatelet therapy (rivaroxaban: risk ratio (RR) 1.67, 95% confidence interval (CI) 1.13 to 2.46; studies = 1, participants = 1644; moderate-certainty evidence; apixaban: RR 1.71, 95% CI 0.97 to 3.02; studies = 1, participants = 1049; low-certainty evidence), while edoxaban may result in little or no difference (RR 1.59, 95% CI 0.27 to 9.36; studies = 1, participants = 229; low-certainty evidence). Low-certainty evidence suggests little or no difference between rivaroxaban, apixaban, or edoxaban and antiplatelet therapy in cardiovascular mortality (rivaroxaban: RR 1.28, 95% CI 0.78 to 2.10; studies = 1, participants = 1644; apixaban: RR 1.30, 95% CI 0.64 to 2.65; studies = 1, participants = 1049; edoxaban: RR 7.44, 95% CI 0.39 to 142.38; studies = 1, participants = 229) and between rivaroxaban or edoxaban and antiplatelets in stroke (rivaroxaban: RR 1.19, 95% CI 0.71 to 2.00; studies = 1, participants = 1644; edoxaban: RR 1.06, 95% CI 0.15 to 7.42; studies = 1, participants = 229). While rivaroxaban versus antiplatelets probably increases major bleeding after TAVR (RR 1.98, 95% CI 1.07 to 3.65; studies = 1, participants = 1644; moderate-certainty evidence), there may be little or no difference between apixaban and antiplatelet therapy (RR 1.07, 95% CI 0.70 to 1.64; studies = 1, participants = 1049; low-certainty evidence). It is unclear if edoxaban has an effect on major bleeding, although the point estimate suggests increased bleeding (versus antiplatelets: RR 2.13, 95% CI 0.54 to 8.30; studies = 1, participants = 229; low-certainty evidence).
In people with an indication for anticoagulation, low-certainty evidence suggests apixaban or edoxaban may result in little to no difference in our predefined primary efficacy outcomes after TAVR when compared to VKA (all-cause mortality: apixaban: RR 1.02, 95% CI 0.59 to 1.77; studies = 1, participants = 451; edoxaban: RR 0.91, 95% CI 0.69 to 1.20; studies = 1, participants = 1426; cardiovascular mortality: apixaban: RR 1.43, 95% CI 0.76 to 2.70; studies = 1, participants = 451; edoxaban: RR 1.07, 95% CI 0.72 to 1.57; studies = 1, participants = 1426; stroke: apixaban: RR 1.28, 95% CI 0.35 to 4.70; studies = 1, participants = 451; edoxaban: RR 0.83, 95% CI 0.51 to 1.34; studies = 1, participants = 1426). While apixaban may result in a similar rate of bleeding as VKA in this population, edoxaban probably increases major bleeding after TAVR in people with an indication for anticoagulation (apixaban: RR 0.90, 95% CI 0.53 to 1.54; studies = 1, participants = 451; low-certainty evidence; edoxaban: RR 1.44, 95% CI 1.08 to 1.93; studies = 1, participants = 1426; moderate-certainty evidence).