STOPDAPT-2 ACS trial inconclusive for 1- vs. 12-month DAPT after PCI and DES implantation
Despite fewer bleeding events, 1-month dual antiplatelet therapy with clopidogrel failed to prove noninferiority vs. 12-month DAPT after PCI and stent implantation for ACS, according to a presenter.
“[STOPDAPT-2 ACS was] inconclusive for the primary endpoint, and numerical increase in the cardiovascular events with clopidogrel monotherapy is worrisome despite reduction in major bleeding,” Hirotoshi Watanabe, MD, PhD, interventional cardiologist and assistant professor in the department of cardiovascular medicine at Kyoto University Hospital in Japan, said during a presentation at the European Society of Cardiology Congress. “Event rate was lower than anticipated, rendering the present study underpowered.”
As Healio previously reported, the results of the STOPDAPT-2 trial demonstrated that shorter duration DAPT after PCI while continuing P2Y12 inhibitor monotherapy did not increase the risk for MI, death or stroke compared with 1 year of standard therapy.
For the STOPDAPT-2 ACS trial, the researchers again evaluated the safety and efficacy of 1-month DAPT compared with 12-month DAPT, but in patients with ACS who underwent PCI with a cobalt-chromium everolimus-eluting stent. The primary endpoint was a composite of major CV (CV death, MI, stent thrombosis and stroke) and bleeding events (major thrombolysis MI and minor bleeding events).
The researchers enrolled an additional 3,000 patients on top of those already enrolled in STOPDAPT-2 who had ACS.
In the overall intention-to-treat analysis, 4,136 patients with ACS and an implanted drug-eluting stent (mean age, 67 years; 79% men) were randomly assigned to 1- or 12-month DAPT plus clopidogrel monotherapy and followed for 1 year. Procedural characteristics, including radial approach, number of target lesions, stent dimensions and number of target vessels, were similar between groups.
Researchers found that 1-month DAPT failed to meet noninferiority compared with 12-month DAPT for the primary endpoint at 1 year (3.2% vs. 2.8%; HR = 1.14; 95% CI, 0.8-1.62; P for noninferiority = .06); a finding mainly driven by higher incidence of CV death/MI/stent thrombosis/stroke in the 1-month arm (HR = 1.5; 95% CI, 0.99-2.26).
Participants in the 1-month DAPT group experienced lower incidence of TIMI major or minor bleeding compared with the 12-month arm (1.11% vs. 0.54%; HR = 0.4; 95% CI, 0.23-0.94).
Of the individual components of the CV event composite endpoint, the risk for MI was greater in the 1-month DAPT arm compared with the 12-month group at 1 year (HR = 1.91; 95% CI, 1.06-3.44).
Moreover, risk for Bleeding Academic Research Consortium (BARC) type 3/5 bleeding at 1 year was lower in the 1-month compared with the 12-month DAPT group (HR = 0.41; 95% CI, 0.2-0.83).
“In ACS patients who underwent successful PCI using [cobalt-chromium]-EES, clopidogrel monotherapy after 1-month DAPT failed to attest the noninferiority to 12-month DAPT with aspirin and clopidogrel for the net clinical benefit with a numerical increase in cardiovascular events despite a reduction in major bleeding events,” Watanabe said during the presentation. “Further investigations are needed to establish the optimal antiplatelet therapy after PCI in patients with ACS.”
In a discussion following the presentation, Robert A. Byrne, MB BCh, PhD, director of cardiology at Mater Private Hospital, Dublin, chair of cardiovascular research at the RCSI University of Medicine and Health Sciences and head of the Cardiovascular Research Institute Dublin, said variability of clopidogrel response may explain the results.
“In patients undergoing PCI for acute coronary syndrome, the results of this trial do not support the use of very short duration DAPT followed by P2Y12 inhibitor monotherapy with clopidogrel as compared to standard treatment,” Byrne said. “Although major bleeding was significantly reduced with this approach, there appeared to be an increase in adverse ischemic events and there was an adverse association related to overall mortality.
“A mechanistic explanation for this signal of harm is the relatively low potency and high variability in treatment response seen with clopidogrel. This is of particular clinical relevance in the early aftermath of an acute coronary syndrome,” Byrne said.
Collapse
Watanabe H. Hot Line: STOPDAPT-2 ACS. Presented at: European Society of Cardiology Congress; Aug. 27-30, 2021 (virtual meeting).