ACC.17: Subclinical leaflet thrombosis occurs more often in TAVR versus SAVR patients

Subclinical leaflet thrombosis occurred in 13.6 percent of patients undergoing transcatheter aortic valve replacement (TAVR) and 3.8 percent of patients undergoing surgical aortic valve replacement (SAVR), according to an analysis of two registries.

The researchers found that subclinical leaflet thrombosis was associated with increased rates of transient ischemic attacks (TIA) and strokes. They defined subclinical leaflet thrombosis as the presence of reduced leaflet motion as well as corresponding hypoattenuating lesions shown with CT scans.

The study also found that anticoagulation with novel anticoagulants and warfarin was effective at preventing or treating subclinical leaflet thrombosis. Dual antiplatelet therapy was not associated with preventing or treating subclinical leaflet thrombosis.

Lead researcher Raj R. Makkar, MD, PhD, of the Cedars-Sinai Heart Institute in Los Angeles, presented results of the studies in a late-breaking clinical trial session at the ACC scientific session on March 19 in Washington, D.C.

The findings were simultaneously published online in the Lancet.

“Our study findings substantiate that anticoagulation with either [novel oral anticoagulants] or warfarin, but not antiplatelet therapy, which is the current standard of care, effectively prevents and treats subclinical leaflet thrombosis; however, whether or not this treatment results in acceptable levels of bleeding and a reduction in the rates of TIA and stroke will be established by the results of the current randomized clinical trials (GALILEO and ATLANTIS study),” the researchers wrote. “Our study findings can help optimize adjunctive pharmacotherapy in patients with bioprosthetic aortic valves, which might potentially result in further improvement in valve hemodynamics and clinical outcomes.”

The study examined patients who enrolled in the RESOLVE registry at Cedars-Sinai Medical Center between Dec. 22, 2014 and Jan. 18, 2017 and the SAVORY registry at Rigshospitalet in Copenhagen, Denmark, between June 2, 2014, and Sept. 28, 2016.

The 890 patients in this analysis underwent TAVR or SAVR and had interpretable CT scans that were analyzed at Cedars-Sinai Heart Institute. More than 84 percent of the patients underwent TAVR.

Patients in the SAVR group were younger (a mean of 71.9 years old versus a mean of 80.7 years old for the TAVR group) and had fewer comorbidities than the TAVR group, including chronic kidney disease, hypertension, hyperlipidemia and congestive heart failure.

The median time from aortic valve replacement to CT scanning was 83 days, including 163 days in the SAVR group and 58 days in the TAVR group.

Overall, 12 percent of patients had reduced leaflet motion. Among the TAVR group, reduced leaflet motion occurred in 5 percent of patients who received the Sapien valve (Edwards Lifesciences), 10 percent who received the Sapien XT valve (Edwards Lifesciences), 16 percent who received the Sapien 3 valve (Edwards Lifesciences), 4 percent who received the CoreValve (Medtronic), 8 percent who received the Evolut (Medtronic) and 14 percent who received the Lotus valve (Boston Scientific).

A multivariable analysis found that significant predictors of reduced leaflet motion included TAVR, increased age, low ejection fraction and absence of anticoagulation at the time of the index CT scan. The researchers added that the time from aortic valve replacement to the CT scan was not a significant predictor of reduced leaflet motion.

The researchers mentioned that reduced leaflet motion occurred in 4 percent of patients receiving anticoagulation, 15 percent of patients who received dual antiplatelet therapy, 16 percent of patients who received monoantiplatelet therapy and 15 percent of patients who did receive anticoagulants. Reduced leaflet motion occurred in 3 percent of patients receiving novel oral anticoagulants and 4 percent of patients receiving warfarin, which was not a statistically significant difference.

Of the 58 patients with reduced leaflet motion who had follow-up imaging, anticoagulation for three months was associated with restoration of normal leaflet motion in all of the patients. Meanwhile, 91 percent of patients who did not receive anticoagulation had persistent or progressive reduced leaflet motion.

“We need to further study whether routine anticoagulation may be useful for this patient population,” Makkar said in a news release. “Dual antiplatelet therapy was not effective in preventing and treating subclinical leaflet thrombosis, and it does have a small risk of bleeding, particularly in older patients. There is an impetus to study the risks and benefits of dual antiplatelet therapy further in randomized clinical trials.”

The researchers acknowledged a few limitations of the study, including its observational design and the potential effect of unmeasured confounders. Patients also did not receive a prospective neurological assessment during their follow-up visits, so the event rates could be underestimated. In addition, some patients did not have consecutive CT scans at regular time intervals, which meant the researchers could not assess the time interval between subclinical leaflet thrombosis and clinical events.

“Our findings question the guidelines recommending [dual antiplatelet therapy] after TAVR and raise the issue of whether or not warfarin or [novel oral antiocoagulants] are more appropriate in certain patients than is [dual antiplatelet therapy],” the researchers wrote. “
The risk-benefit profile of anticoagulation will be established in future clinical trials. Despite excellent outcomes after TAVR with the new-generation valves, room might exist for further improvement in outcomes through an understanding of the predictors of reduced lea et motion and consideration of a short course of anticoagulation if findings from ongoing randomized trials substantiate these existing findings.”