PARIS (FRONTLINE MEDICAL NEWS) – Single-antiplatelet therapy with low-dose aspirin following transcatheter aortic valve replacement (TAVR) reduced the occurrence of major adverse events, compared with guideline-recommended dual-antiplatelet therapy (DAPT), in the randomized ARTE trial.

The TAVR guideline recommendation for DAPT with low-dose aspirin plus clopidogrel is not based on evidence. It relies on expert opinion. ARTE (Aspirin Versus Aspirin + Clopidogrel Following TAVR) is the first sizable randomized trial to address the safety and efficacy of aspirin alone versus DAPT in the setting of TAVR, Josep Rodés-Cabau, MD , noted in presenting the ARTE results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

Although a confirmatory randomized trial would be welcome, “in the meantime, the results of the ARTE trial may help us to guide clinical practice beyond empirical recommendations,” he said. “At the Quebec Heart and Lung Institute, we’ve stopped using DAPT completely for our TAVR patients unless they have a specific indication for it, such as a recently implanted coronary stent.”

ARTE was a multicenter, prospective, international open-label study of 222 TAVR patients who were randomized to 3 months of single-antiplatelet therapy (SAPT) with aspirin at 80-100 mg/day or to DAPT with aspirin at 80-100 mg/day plus clopidogrel at 75 mg/day after a single 300-mg loading dose. Participants had a mean Society of Thoracic Surgery Predicted Risk of Mortality score of 6.3%. The vast majority of participants received the balloon-expandable Edwards Lifesciences Sapien XT valve. The remainder got the Sapien 3 valve.

The primary outcome was the 3-month composite of death, MI, major or life-threatening bleeding, or stroke or transient ischemic attack. It occurred in 15.3% of the DAPT group and 7.2% on SAPT, a difference that didn’t reach statistical significance (P = .065) because of small patient numbers.

ARTE was halted prematurely. The original plan was to recruit 300 TAVR patients for 12 months of follow-up. However, the investigators wound up capping the trial at 220 patients and 3 months of follow-up because of slow enrollment and withdrawal of financial support by the study sponsors. As a result, while all of the components of the composite endpoint showed strong, consistent benefit favoring SAPT, only the difference in major or life-threatening bleeding achieved statistical significance (see graphic).

All subjects were on a proton pump inhibitor. The type, timing, and severity of bleeding events differed between the two study arms. All 4 bleeding events in the SAPT group were vascular in nature, while 5 of the 12 in the DAPT group were gastrointestinal. All the bleeding events in the SAPT group occurred within 72 hours after TAVR, whereas 5 of 12 in the DAPT recipients occurred later. Only one patient on SAPT experienced life-threatening bleeding, compared with seven DAPT patients who did.

“There were two prior smaller studies before ours,” according to Dr. Rodés-Cabau of Laval University in Quebec City. “One showed no differences, and an Italian one showed a tendency toward more bleeding with DAPT. So, I think there has been no sign to date that adding clopidogrel protects this group of patients from anything.”

Discussant Luis Nombela-Franco, MD, an interventional cardiologist at San Carlos Hospital in Madrid, pronounced the ARTE trial guideline-changing despite its limitations.

ARTE was supported by grants from Edwards Lifesciences and the Quebec Heart and Lung Institute.

Simultaneous with Dr. Rodés-Cabau’s presentation in Paris, the ARTE trial was published online (JACC Cardiovasc Interv. 2017 May 11. pii: S1936-8798[17]30812-9).