Clopidogrel may be omitted in patients on OAC after TAVI

In patients on long-term oral anticoagulant (OAC) therapy who are undergoing transcatheter aortic valve implantation (TAVI), post-procedure use of clopidogrel can be omitted to reduce bleeding without compromising antithrombotic efficacy, according to results from cohort B of the POPular TAVI trial presented at the American College of Cardiology and World Congress of Cardiology virtual meeting (ACC.20/WCC).

The cohort included 326 patients undergoing TAVI who had an established indication for long-term OAC therapy. Recruited from 17 European sites, the patients were randomized (1:1) to receive open-label treatment with OAC monotherapy or OAC plus 3 months of clopidogrel. Among 313 patients (mean age, 81 years; 45.4 percent female) who completed 12-month follow-up, 95.5 percent of those receiving OAC alone and 94.2 percent of those receiving OAC plus clopidogrel had atrial fibrillation (AF). Adherence to clopidogrel was 95.5 percent over 3 months. [Nijenhuis VJ, et al, ACC.20/WCC, abstract 405-08; N Engl J Med 2020, doi: 10.1056/NEJMoa1915152]

Results demonstrated superiority with OAC alone vs OAC plus clopidogrel in the co-primary outcomes of all bleeding (according to Valve Academic Research Consortium-2 [VARC-2] definitions) and non–procedure-related bleeding (all VARC-2 bleeding, excluding Bleeding Academic Research Consortium [BARC] type 4 severe bleeding), according to investigator Dr Vincent J Nijenhuis of the St Antonius Hospital, Nieuwegein, the Netherlands.

“At 12 months, all bleeding occurred in 21.7 percent of patients receiving OAC alone compared with 34.6 percent of patients receiving OAC plus clopidogrel, with a risk ratio [RR] of 0.63 [95 percent confidence interval (CI), 0.43 to 0.90; p=0.011]. Non-procedural bleeding occurred in 21.7 percent vs 34 percent of the patients, with an RR of 0.64 [95 percent CI, 0.44 to 0.92; p=0.015],” reported Nijenhuis.

Most bleeding events occurred within the first month, with the TAVI access site being the most common location of bleeding in both the OAC alone group (44 percent) and the OAC plus clopidogrel group (50 percent). These bleeding events were not of BARC type 4, and were thus classified as non–procedure-related bleeding.

The use of OAC alone was also at least noninferior to OAC plus clopidogrel for the secondary composite outcome of cardiovascular (CV) mortality, non–procedure-related bleeding, stroke or MI, as well as that of CV mortality, ischaemic stroke or MI.

At 12 months, CV mortality, non–procedure-related bleeding, stroke or MI occurred in 31.2 percent of patients receiving OAC alone vs 45.5 percent of those receiving OAC plus clopidogrel (difference, -14.3 percent [noninferiority margin, 7.5 percent]; 95 percent CI for noninferiority, -25 to -3.6; RR, 0.69; 95 percent CI for superiority, 0.51 to 0.92). The composite outcome of CV mortality, ischaemic stroke or MI was reported in 13.4 percent vs 17.3 percent of the patients (difference, -3.9 percent [noninferiority margin, 7.5 percent]; 95 percent CI for noninferiority, -11.9 to 4.0 ; RR, 0.77; 95 percent CI for superiority, 0.46 to 1.31).

Rates of all-cause mortality (13.4 percent vs 15.4 percent; RR, 0.87; 95 percent CI, 0.51 to 1.50) and ischaemic stroke (5.1 percent vs 5.8 percent; RR, 0.88; 95 percent CI, 0.35 to 2.23) were similar between patients on OAC alone and those on OAC plus clopidogrel.

“Major, life-threatening or disabling bleeding was reduced with OAC alone vs OAC plus clopidogrel [8.9 percent vs 16.7 percent; RR, 0.54; 95 percent CI, 0.29 to 0.99],” said Nijenhuis.

In the study, most patients received vitamin K antagonists as OAC therapy (75.2 percent in the OAC alone group vs 70.5 percent in the OAC plus clopidogrel group). Direct oral anticoagulants were used by 23.6 percent vs 29.5 percent of the patients.

A majority of patients in both groups underwent TAVI with a transfemoral approach (86.6 percent vs 84.6 percent). VARC-2 vascular complications occurred in 12.7 percent vs 22.4 percent of the patients.

“In conclusion, our results show that in patients with an established indication for OAC who are undergoing TAVI, OAC alone reduces the rate of bleeding events, including major, life-threatening or disabling bleeding, without increasing the rate of thrombotic events as compared with OAC plus clopidogrel,” said Nijenhuis.