Analysis of the prospective Fuwai PCI Registry using selection criteria from the TWILIGHT trial, has concluded that long-term dual antiplatelet therapy (DAPT) remains an optimal treatment option for acute coronary syndrome patients (ACS) following percutaneous coronary intervention (PCI). This is contrary to the findings of other recent evidence pointing towards the withdrawal of aspirin early-on after the start of antiplatelet therapy, according to the authors.
The study, presented during a late-breaking trial session at the Society for Cardiovascular Angiography & Interventions 2021 scientific sessions (SCAI 2021, 28 April–1 May, virtual) by Hao-Yu Wang (Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China), concluded that long-term DAPT reduces ischaemic events without increasing bleeding or other complications compared to short-term DAPT treatments.
Patients with ACS are given a dual course of antiplatelet therapy—comprising aspirin and an oral P2Y12 inhibitor, including ticagrelor or clopidogrel—to reduce their risk of ischaemic events after PCI. According to Hao-Yu Wang and colleagues, “recent emphasis” on reduced duration or intensity of antiplatelet therapy following PCI, irrespective of indication, may fail to account for the substantial risk of subsequent non-target lesion events in ACS patients.
The study team sought to investigate the benefits of extended-term (>12-month) DAPT as compared with short-term DAPT in high-risk ACS patients undergoing PCI. To do this they analysed patients from the Fuwai PCI registry, defined by at least one clinical and one angiographic feature based on the selection criteria used in the TWILIGHT trial.
Findings from TWILIGHT were presented at the Transcatheter Cardiovascular Therapeutics scientific symposium in 2019 (TCT 2019; 25–29 September, San Francisco, USA). The study concluded that ticagrelor monotherapy after three months of DAPT reduces bleeding events without increasing the risk of death, myocardial infarction (MI), or stroke in high-risk patients who have undergone successful PCI. A subsequent subanalysis of the TWILIGHT trial—TWILIGHT-ACS—which included 5,739 patients with non-ST elevation acute coronary syndromes (NSTE-ACS) concluded that ticagrelor monotherapy reduced the risk of clinically relevant bleeding compared to DAPT over 12 months.
During their study, Hao-Yu Wang and colleagues analysed data from 4,875 high-risk “TWILIGHT-like” patients with ACS who were event-free at 12 months after PCI. The primary outcome was the composite of all-cause death, MI, or stroke at 30 months while BARC type 2, 3, or 5 bleeding was the key secondary outcome.
Results showed that slightly more than two-thirds of ACS patients remained on DAPT beyond 12 months after PCI, while extended DAPT compared with shorter DAPT reduced the composite outcome of all-cause death, MI or stroke by 63%. BARC type 2, 3, or 5 bleeding rates did not differ significantly in patients treated with DAPT longer than 12-months versus those treated with DAPT less than 12-months, Hao-Yu Wang reported. The effect of long-term DAPT on primary and key secondary outcomes across the proportion of ACS patients with one‒three, four‒five, or six‒nine risk factors showed a consistent manner.
Discussing the findings, Hao-Yu Wang commented that the current study appeared “somewhat discordant” with the TWILIGHT-ACS findings, which demonstrated the potential benefit of ticagrelor monotherapy, after three-months of DAPT, in halving clinically relevant bleeding events without a negative impact on composite ischaemic events, compared with ticagrelor plus aspirin in patients with NSTE-ACS.
The hazard ratio for MACE in TWILIGHT-ACS trial was 0.96 for placebo versus aspirin, with an upper confidence interval of 1.28, meaning that the level of risk reduction seen with clopidogrel-based DAPT in the DAPT trial (29% relative risk reduction) and ticagrelor-based DAPT in PEGASUS-TIMI 54 trial (15-16% relative risk reduction) could not be confidently excluded, particularly in those with more risk factors in whom the hazard ratios and upper confidence intervals were higher, Hao-Yu Wang commented. Moreover, patients with STEMI were not included in TWILIGHT-ACS data and the proportion of patients with additional ≥4 clinical and angiographic risk factors were relatively lower than the present study’s high-risk ACS cohort (65.8 vs. 80.3%). In addition, the findings of TWILIGHT-ACS substudy cannot be generalised to patients treated with clopidogrel given that all patients with NSTEACS received ticagrelor as the P2Y12 inhibitor.
“Our study extended theses earlier results to a high-risk ACS cohort (including STEMI patients) by providing the benefits of long-term DAPT with respect to ischaemic events are preserved via clopidogrel. Due to current evidence, an early single antiplatelet therapy with a potent P2Y12 inhibitor after a short period of DAPT may be reasonable among ACS patients, potentially leaving a standard 12 month or longer DAPT (with possible de-escalation if not done before, or association of low dose rivaroxaban plus aspirin) to high-risk ACS patients with extensive coronary disease and complex target-lesion anatomy, and therefore at high risk for ischemic recurrences in the presence of low risk of bleedings. Further prospective trials specifically targeting patients with ACS are required to clarify this issue,” the study’s authors told Cardiovascular News.
“Our findings suggested that prolonged DAPT in ACS patients who present with a particularly higher risk for thrombotic complications without excessive risk,” said Hao-Yu Wang. “Not only did we see long-term DAPT was associated with a lower risk of a major cardiovascular event without an increase in bleeding events, but it could be considered an effective strategy to balance the risk for bleeding and ischaemia in high-risk patients with ACS. Our results reinforce prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care.”