A shorter course of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) was found to be non-inferior to standard DAPT up to 12 months, results of the XIENCE 90 and 28 clinical trials, presented at TCT Connect 2020 (14–18 October, virtual) by Roxanna Mehran (Icahn School of Medicine, New York, USA) suggest. The XIENCE 28 and XIENCE 90 trials were prospective, single-arm, multicentre, open-label non-randomised trials conducted to evaluate the safety of one-month (28) or three-month (90) DAPT in high-bleeding risk patients undergoing PCI with the XIENCE everolimus-eluting stent (Abbott).
Extended duration of DAPT after PCI increases the risk of bleeding, which is associated to worse outcomes and quality of life, especially among patients at high bleeding risk. Recent clinical trials on newer generation drug-eluting stents have shown an acceptable safety profile with a short course of DAPT. However, the optimal DAPT duration in HBR patients undergoing PCI remains unknown.
The primary endpoint in the two XIENCE trials evaluated safety (all-cause death or myocardial infarction) of a short DAPT regimen (one or three months) compared to DAPT up to 12 months. The secondary endpoints were the incidence of clinically relevant bleeding (BARC 2‒5) and stent thrombosis (definite/probable) against a performance goal (only for XIENCE 90). The XIENCE V USA post-approval study served as the historical control group through a propensity score stratified analysis.
After successful PCI, enrolled patients in XIENCE 28 were prescribed one month of DAPT while patients in XIENCE 90 were prescribed three months of DAPT. Those who were free from ischaemic events and adhered to the antiplatelet regimen during the first one month or three months received “one-month” or “three-month” clear assessments. Clear subjects were eligible to be placed on antiplatelet monotherapy (aspirin) from one or three months to 12 months.
XIENCE 90 involved a total of 2,047 high bleeding risk subjects from 106 sites across the USA. According to Mehran, the trial demonstrated similar rates of all death or MI between three and 12 months in the test group versus the control (5.4% vs. 5.4%, one-sided 97.5% UCL: 2.23%, p non-inferiority=0.0063).
XIENCE 28 enrolled a total of 1,605 high bleeding risk subjects, and according to Mehran also demonstrated non-inferiority of death or MI in the test group between one and six months (3.5% vs. 4.3%, one-sided 97.5% UCL: 0.97%, p non-inferiority=0.0005). For the secondary endpoint, the incidence of bleeding (BARC 2-5) was 5.1% vs. 7.0% (p superiority=0.0687 in XIENCE 90 and 4.9% vs. 5.9% (p superiority=0.19) in XIENCE 28. Major bleeding (BARC 3-5) was significantly reduced in both trials (XIENCE 90: 2.2% vs. 6.3%, p superiority<0.0001; XIENCE 28: 2.2% vs. 4.5%, p superiority=0.0156).
“Among high bleeding risk patients undergoing PCI with the XIENCE stent, a short DAPT regimen of one or three months compared with standard DAPT up to 12 months resulted in non-inferior ischaemic outcomes and similar rates of clinically relevant (BARC 2–5 ) bleeding, with a significant reduction in major (BARC 3–5) bleeding,” said Mehran. “Additionally, there was a very low incidence of stent thrombosis.”
In a press release issued alongside the XIENCE 90 and 28 results, Nick West, divisional vice president, medical affairs, and chief medical officer in Abbott’s vascular business, said: “Since the initial launch more than ten years ago, the XIENCE family of stents has become the gold-standard in coronary drug-eluting stents. With the Short DAPT program, our goal is ultimately to find the optimal duration of use of blood thinning medication for individual patients by providing tailored treatment options to minimize the risk of potentially fatal bleeding events and to help them return to their daily lives as quickly as possible.”