Routine Anticoagulation Seems Warranted After TMVR: Review

(UPDATED) To help manage thrombotic risk after transcatheter mitral valve replacement (TMVR), clinicians should consider routine use of oral anticoagulation and regular clinical and imaging follow-up, authors of a new review conclude.

Numerous TMVR systems are being developed for patients with severe symptomatic mitral regurgitation (MR), up to half of whom are considered to be too high risk for surgical repair or replacement. Early studies have provided promising results, but as with any bioprosthetic valves delivered surgically or percutaneously, there is the potential for thrombosis.

In the December 9, 2019, issue of JACC: Cardiovascular Interventions, lead author Matteo Pagnesi, MD (San Raffaele Scientific Institute, Milan, Italy), and colleagues review the current evidence regarding the thrombotic risk after TMVR—which is limited—as well as the antithrombotic strategies to mitigate it.

Senior author Azeem Latib, MD (Montefiore Medical Center, Bronx, NY), told TCTMD, “We thought that it was a good time to look at all the data we do have available to understand what is probably going to be one of the biggest challenges with transcatheter mitral valve replacement, which is really the risk of thrombosis. . . . It just seemed like this is the right moment to start a discussion about where we’re going with these devices.”

Randomized trials are still needed to sort out the best antithrombotic strategies for patients undergoing TMVR, but this paper was needed to make clinicians aware that valve thrombosis is a major issue in this setting, probably a bigger one than in aortic interventions, Latib said. Much of that added risk, he explained, is related to the larger devices needed in the mitral valve.

As for what the antithrombotic strategy should be while the developing field awaits more data, Latib said that he has been putting all of his patients undergoing TMVR on oral anticoagulation with a vitamin K antagonist (VKA) even if they’re in sinus rhythm.

No ‘Robust’ Data

Due to the lack of evidence regarding antithrombotic strategies after TMVR, Pagnesi et al begin their review by looking at the literature on surgical bioprosthetic aortic or mitral valve replacement. In the aortic space, there are data suggesting that embolic events are reduced with a combination of warfarin and aspirin, with some evidence that extending anticoagulation for up to 6 months improves survival and reduces stroke and other thromboembolic events at the cost of more bleeding.

There are no “robust” studies on surgical bioprosthetic MV replacement, but the authors say that thrombotic risk appears to be higher here when compared with aortic operations.

“The rationale for anticoagulation in the first months after bioprosthesis implantation is to decrease the risk of thromboembolic events until the prosthetic valve is fully endothelialized; furthermore, local blood flow perturbations around the valve prosthesis (that could be even more relevant in the mitral position compared with the aortic one) and patient-related risk factors (atrial fibrillation, suboptimal anticoagulation, history of prior thromboembolic events, left ventricular dysfunction, known hypercoagulable condition) may play a crucial pathogenetic role in bioprosthetic valve thrombosis,” Pagnesi et al write.

They point out that European and US guidelines recommend consideration of oral anticoagulation using a VKA for 3 to 6 months after surgical bioprosthetic MV replacement.

However, there are no recommendations for antithrombotic therapy after TMVR, a procedure still in the early stages of development. A review of studies on TMVR for native disease, degenerated bioprostheses (valve-in-valve), failed annuloplasty (valve-in-ring), and severe mitral annular calcification (valve-in-MAC) showed rates of valve thrombosis ranging from about 6% to 14.4% over various lengths of follow-up.

Most patients received a VKA plus aspirin at discharge, and there are hints in the data to suggest that this strategy cuts the risk of thrombosis relative to not being on oral anticoagulation.

“Hence, it seems reasonable to prescribe oral anticoagulation with VKA in the first months after any TMVR procedure in patients who do not have an indication for long-term anticoagulation to mitigate the risk of transcatheter heart valve thrombosis,” the authors say. “The duration of anticoagulant therapy and the eventual association of antiplatelet therapy could be tailored through a careful evaluation of the patient’s individual bleeding risk, even though this strategy is empirical and not based on dedicated studies.”

Late Valve Thrombosis

Pagnesi et al also raise the issue of late valve thrombosis occurring after the initial postprocedural period covered by oral anticoagulation therapy.

“Considering the wide time frame of device thrombosis after TMVR, serial echocardiographic surveillance and clinical follow-up is fundamental to promptly detect and treat thrombotic transcatheter heart valve dysfunction,” they say.

More specifically, they advise: “In cases of clinical suspicion (new-onset heart failure symptoms with acute or subacute presentation, new thromboembolic events) and suggestive transthoracic echocardiographic features of transcatheter heart valve thrombosis (direct visualization of thrombus in rare cases, 50% mean gradient increase, thickened cusps, restricted leaflet mobility), prompt evaluation with transesophageal echocardiography or [CT] scan is indicated, with specific treatment according to clinical presentation and patients’ profile in cases of confirmed transcatheter heart valve thrombosis (initiation or intensification of anticoagulation, thrombolysis, surgery, or transcatheter valve-in-valve).”

Some patients will have such a high bleeding risk that anticoagulation may not be advisable, the authors note, and close follow-up will be important in this scenario, too.

“In patients deemed to be at very high (prohibitive) bleeding risk, with an expected risk of anticoagulant-related bleeding events potentially higher and more concerning than the transcatheter heart valve-related thromboembolic risk, the adoption of an antiplatelet-only strategy without anticoagulation seems to be inevitable,” they say. “In these cases, we recommend a strict clinical and imaging follow-up to exclude the occurrence of . . . thrombosis.”