The ARTE study, which was simultaneously presented at EuroPCR (16–19 May, Paris, France) and published in JACC: Cardiovascular Interventions, indicates that dual antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI)—the current standard approach for reducing the risk of ischaemic events—is associated with a significant increase in the three-month rate of major/life-threatening bleeding events compared with aspirin monotherapy. Furthermore, there were no significant differences between DAPT and aspirin monotherapy in the rates of myocardial infarction, death or ischaemic stroke/transient ischaemic attacks.
Writing in the journal, Josep Rodés-Cabau (Quebec Heart & Lung Institute, Laval University, Quebec City, Canada) and others report that DAPT is recommended for one to six months after a TAVI procedure to reduce the risk of ischaemic events. However, they note that this recommendation is a “on an empirical basis” and that “no studies have as yet shown the efficacy of aspirin and clopidogrel vs. aspirin alone or no antithrombotic treatment in preventing ischaemic events following TAVI procedures”. The authors add that it would be of “major clinical relevance to determine the risk/benefit ratio of using dual antithrombotic therapy following TAVI procedures”.
The aim of the ARTE trial, therefore, was to compare aspirin and clopidogrel (ie. DAPT) with aspirin monotherapy as antithrombotic treatments following TAVI for the prevention of ischaemic events (myocardial infarction, stroke, or transient ischaemic attack), major/life-threatening bleeding events or death. Of 222 patients scheduled to undergo TAVI with a balloon-expandable device (92% received Sapien XT, Edwards Lifesciences), 111 were randomised to receive DAPT and 111 were randomised to receive aspirin monotherapy. The primary endpoint was the rate of death, myocardial infarction, stroke or transient ischaemic attack, major/life-threatening bleeding events or death at three months.
Overall, there were no significant differences between groups in the rate of the primary endpoint—although, the rate tended to be higher in patients receiving DAPT: 15.3% vs. 7.2% for aspirin monotherapy (p=0.065).Furthermore, there were no significant differences in the rates of death, myocardial infarction, or ischaemic stroke/transient ischaemic attack between groups.
According to Rodés-Cabau et al, several observational studies have already indicated that DAPT does not provide benefit over aspirin monotherapy in terms of preventing cerebrovascular event after TAVI. The authors say that there may be several reasons as to why DAPT does not appear to reduce the risk of such events, including that “at least” half of strokes within the first 30 days occur immediately after or 24 hours post procedure and seem to be related to the procedure itself and that a significant proportion of strokes that occur after the first 24 hours “seem to be related to the occurrence of atrial arrhythmias, for which DAPT has demonstrated limited value”.
Furthermore, as well as not appearing to provide any benefit over aspirin monotherapy, DAPT was associated with a significantly higher rate of major/life-threatening bleeding events: 10.8% vs. 3.6% for the aspirin monotherapy (p=0.038). Rodés-Cabau et al comment: “There were eight life-threatening bleeding events (3.6%) and all but one occurred in the DAPT group. There five gastrointestinal bleeding events and all of them occurred in the DAPT group.” They add that this finding confirms those of previous studies, noting that an going study—POPULAR-TAVI—comparing aspirin monotherapy with DAPT following TAVI that has bleeding events as the single primary outcome “should provide further detail data for the safety benefits of using aspirin monotherapy in TAVI candidates”.
Commenting that a previous study found that DAPT did not prevent subclinical valve thrombosis, Rodés-Cabau et al note that they did not find any differences in valve haemodynamics between groups early after TAVI and no patient exhibited a significant increase in transvalvular gradients.. However, no computed tomogrpahy post-TAVI data was available in this study for evaluating subclinical valve thrombosis.
They conclude: “In this small trial, aspirin monotherapy (vs. DAPT) was associated with a tendency towards a lower rate of adverse events following TAVI, mainly driven by a lower rate of serious bleeding events while not increasing the risk of myocardial infarction or stroke. These results should serve to design a definitive trial for determining the optimal antithrombotic treatment in TAVI candidates. Meanwhile, the results of the ARTE trial may help us to guide clinical practice beyond empirical recommendations”
Rodés-Cabau told Cardiovascular News that he felt that “that probably all patients need some form of antithrombotic therapy” after TAVI, but particularly “patients with a high atherosclerotic burden or with atrial arrhythmias, who have a higher risk of ischaemic events”. He adds that, based on the available evidence, he would recommend “single antiplatelet therapy except in patients with atrial arrhythmias requiring anticoagulation therapy”.