Shorter DAPT OK in high bleeding risk patients post-PCI
Treatment with dual antiplatelet therapy (DAPT) after PCI* can safely be shortened to 1 or 3 months without raising ischaemic risk in select patients with high bleeding risk, according to the XIENCE 90/28 trials presented at TCT 2020.
“DAPT is essential for the prevention of ischemic events after PCI but inevitably increases the risk of bleeding, especially in patients at HBR, which constitute up to 40 percent of patients undergoing the procedure,” said lead investigator Professor Roxana Mehran from Icahn School of Medicine at Mount Sinai, New York, New York, US.
One strategy to avoid bleeding is by shortening DAPT, Mehran said. “[While] recent trials on next-generation DES** have shown an acceptable safety profile with a short course of DAPT; the optimal DAPT duration in HBR patients remains unknown.”
Both XIENCE 90 (n=2047) and 28 (n=1,605) were prospective, single-arm, multinational studies which enrolled HBR*** patients who had successfully undergone PCI using the everolimus-eluting XIENCE 90 and 28 stents, respectively. DAPT after PCI comprised aspirin plus a P2Y12 inhibitor — 3 months for XIENCE 90 and 1 month for XIENCE 28 — which was shorter than the conventional DAPT duration. Patients who were event-free subsequently switched to aspirin monotherapy. [TCT 2020, LB session II]
These patients were propensity score-matched and compared against historical controls drawn from the all-comer XIENCE V post-approval study (n=8,061). Patients had longer DAPT in XIENCE V, with 90.5 percent of them being on DAPT at 6 months while 85.6 percent were still on DAPT at 1 year.
In XIENCE 90, the primary outcome of all deaths or myocardial infarction occurred at similar rates as historical controls (5.4 percent vs 5.4 percent; p=0.0063 for noninferiority). Similar results were seen for XIENCE 28, whereby the primary outcome occurred in 3.5 percent of patients compared with 4.3 percent of historical controls (p=0.0005 for noninferiority).
For the powered secondary outcome of BARC type 2–5 bleeding, the rates were lower with shorter DAPT in both XIENCE 90 (5.1 percent vs 7.0 percent; p= 0.0687 for superiority) and XIENCE 28 (4.9 percent vs 5.9 percent; p=0.19 for superiority) compared with historical rates in XIENCE V, although the difference did not meet the superiority criteria.
However, further restricting the analysis to major bleeding (defined as BARC# type 3 to 5) showed that major bleeds were significantly less common with the shorter DAPT in both XIENCE 90 (2.2 percent vs 6.3 percent) and XIENCE 28 (2.2 percent vs 4.5 percent) than the historical cohort — thus meeting the margin for superiority (p<0.0001 and p=0.0156, respectively).
In addition, the rate of definite/probable stent thrombosis based on ARC criteria was 0.20 percent in XIENCE 90, which according to Mehran, was significant in comparison against the performance goal of 1.2 percent (p<0.0001). For XIENCE 28, the rate was identical as that in historical control, at 0.3 percent.
Given that XIENCE V was conducted approximately one decade before the current XIENCE 90/28 studies, confounders related to changes in clinical practice cannot be excluded, Mehran cited as a study limitation.
Not for everyone
During the presentation, Mehran highlighted the extensive list of inclusion and exclusion criteria in patient selection for the study; the latter which involved STEMI, PCI with overlapping stents, plus various criteria for target lesion.
Noting the many exclusion criteria, invited discussant Dr Ziad Ali from Columbia University Medical Center/NewYork-Presbyterian Hospital in New York, New York, US asked what’s left.
“I think it’s not for everyone,” said Mehran, who pointed out these studies looked at more complex patients and lesions. “The observed treatment effect applies only to patients ‘free’ from adverse events and adherent to the DAPT regimen in the first 1 or 3 months post-PCI.”
Also noting that there are previous studies which showed reduced ischaemic events with prolonged DAPT, Ali asked how to reconcile these with the current findings.
To this, patient selection was again brought to the fore. “[The current data] is only applicable to patients with HBR features, who do not derive a benefit from prolonged DAPT and, in fact, shortened DAPT is safer,” said XIENCE V co-investigator Professor Marco Valgimigli of Bern University Hospital, Bern, Switzerland.
“Perhaps in clinical practice, we may want to use a bleeding risk score to properly risk stratify the patient or the recently proposed HBR criteria,” he added.