Presenter: Dr. Hao-Yu Wang

The study was presented by lead author Hao-Yu Wang, MD, from Fuwai Hospital, National Center for Cardiovascular Diseases, and Chinese Academy of Medical Sciences & Peking Union Medical College, China (1). The findings in 4,875 patients showed a 63% reduction in death, myocardial infarction, or stroke for the high-risk patients who remained on DAPT for more than 12 months after PCI, compared to those who stopped treatment sooner. 

Long-term DAPT – upwards of 12 months – is currently recommended for ACS following PCI due to increased risk of ischemic events, in turn raising the risk of arterial blood clots and impacting survival chances, according to an accompanying press statement. Improvements in stent devices in recent years have led to several studies looking at the safety and efficacy of shortening DAPT time to less than 12 months in ACS patients undergoing PCI, although Wang stressed that this has been “controversial.” He cited the SMART-DATE trial, comparing 6 versus 12 months of DAPT after PCI in ACS patients, which found significant risk of spontaneous MI in those who stopped treatment at 6 months compared to those on longer therapy. This recent emphasis on cutting DAPT time may fail to account for potentially heightened risk of de novo atherothrombotic lesions in the entire coronary arterial bed in “vulnerable” post-ACS patients, Wang and the researchers hypothesized.

They, therefore, set out to investigate the risks and benefits of long- versus short-term (>12 months vs. <12 months) DAPT in high-risk ACS patients undergoing PCI. High-risk patients were selected consecutively from the prospective Fuwai PCI Registry based on fulfilling at least one clinical and one angiographic feature from the trial criteria used in the 2019 TWILIGHT study, which assessed the P2Y12 inhibitor ticagrelor after a minimum period of DAPT as an emerging approach to reduce bleeding risk (2). They had each remained event-free 12 months after PCI. TWILIGHT clinical criteria for high-risk including patients being aged at least 65 years, female, having troponin-positive acute coronary syndrome, established vascular disease, diabetes mellitus, chronic kidney disease, and being treated with medication. Angiographic criteria included multivessel coronary artery disease, a total stent length of more than 30 mm, a thrombotic target lesion, a bifurcation lesion treated with two stents, an obstructive left main or proximal left anterior descending lesion, and a calcified target lesion treated with atherectomy.

Longer DAPT treatment time reduced the composite primary outcome of all-cause death, MI, or stroke by 63% compared with shorter DAPT (1.5% vs. 3.8%; adjusted hazard ratio [HR]: 0.374; 95% confidence interval [CI]: 0.256 to 0.548; HR for propensity-matched analysis [matched]: 0.361; 95% CI: 0.221-0.590). The all-cause mortality outcome was driven mostly by a reduction in cardiovascular death, Wang noted. For the secondary outcome, Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding, there was no significant difference between patients on longer and shorter medication plans, however (0.9% vs. 1.3%; adjusted HR: 0.668 [0.379 to 1.178]; HR matched: 0.721 [0.369-1.410]).

The study is believed to be the first to report feasibility and safety of long-term DAPT for high-risk “TWILIGHT-like” patients with ACS treated with a drug-eluting stent, Wang said. The results come in contrast to those of TWILIGHT, which found that in high-risk patients who underwent PCI and completed shorter-term treatment (3 months) with DAPT, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, “with no higher risk of death, myocardial infarction, or stroke. “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 ischemia in high-risk patients with ACS,” said Wang. “Our results reinforce prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care."

In practice, long-term DAPT still appears to be the more widely used strategy, with the researchers concluding that ACS had “higher rates of physician-guided continuation of DAPT beyond 12 months. 

All Authors: Giorgio Medranda, MD; Brian C. Case, MD; Jason P. Wermers, BS; Natalie Morrison, BA (Hons); Ron Waksman, MD, MSCAI. 

References

1. Establishing the Optimal Duration of DAPT After PCI in High-Risk TWILIGHT-like patients with Acute Coronary Syndrome
2. Roxana Mehran, MD, MSCAI; Usman Baber, MD, MS; Samin K. Sharma, MD, MSCAI; David J. Cohen, MD, MSc, FSCAI; Dominick J. Angiolillo, MD, MPH, FSCAI; Carlo Briguori, MD, PhD, FSCAI; Jin Y. Cha, BS; Timothy Collier, MSc; George D. Dangas, MD, PhD, MSCAI; Dariusz Dudek, MD, PhD; Vladimír Džavík, MD, FSCAI; Javier Escaned, MD, PhD, Robert Gil, MD, PhD; Paul A. Gurbel, MD; Christian W. Hamm, MD; Timothy D. Henry, MD, MSCAI; Kurt Huber, MD; Adnan Kastrati, MD; Upendra Kaul, MD, FSCAI; Ran Kornowski, MD; Mitchell Krucoff, MD, FSCAI; Vijay Kunadian, MB, BS, MD; Steven O. Marx, MD, Shamir R. Mehta, MD; David Moliterno, MD; E. Magnus Ohman, MD, FSCAI; Keith G. Oldroyd, MB, ChB, M.D; Gennaro Sardella, MD; Samantha Sartori, PhD; Richard Shlofmitz, MD; P. Gabriel Steg, MD; Giora Weisz, MD, FSCAI; Bernhard Witzenbichler, MD; Ya-ling Han, MD, PhD; Stuart Pocock, PhD; and C. Michael Gibson, M.D. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med 2019;381:2032-2042